Novel cyclohexane derivative, prodrug and salt thereof and diabetes therapeutic agent containing said compounds


FIELD: chemistry; pharmaceutics.

SUBSTANCE: present invention relates to novel cyclohexane derivatives of formula (I) or their pharmaceutically acceptable salts having inhibitory effect on Na+-glucose cotranspoter (SGLT2), as well as to pharmaceutical compositions based on the said compounds and their use in preventing or treating diabetes, diabetic complications caused by hyperglycaemia or obesity. , where A is -O-; n is an equal to 0 or 1; R6 and R7 each independently represents a hydrogen atom or a C1-C6alkyl group, m is an integer selected from 1-3; Q is selected from Q1 - Q5, given in formula 2.

EFFECT: obtaining novel cyclohexane derivatives or their pharmaceutically acceptable salts and preparation of a pharmaceutical composition based on the said compounds.

15 cl, 19 dwg, 11 tbl, 86 ex

 

The technical field

The present invention relates to cyclohexanebis derivatives, their prodrugs and their pharmaceutically acceptable salts which are useful as medicines. In particular, the present invention relates to cyclohexanebis derivatives, their prodrugs and their salts, which are useful as preventive or therapeutic agents, which cause the effect by inhibition of Na+-glucose cotransporter 2 (SGLT2), from diabetes, such as insulin-dependent diabetes mellitus (diabetes type I) and insulin-independent diabetes mellitus (type II diabetes), diabetic complications and diseases such as obesity-induced hyperglycemia.

The level of technology

In recent years, the number of diabetic patients has increased due to preference power on the Western type and the constant lack of exercise, etc. In diabetic patients reduced as the secretion of insulin, and insulin sensitivity as a result of chronic hyperglycemia, and this contributes to a further increase in blood sugar levels, worsening the patient's condition. As therapeutic agents for diabetes used biguanide medicines medicines on the basis of sulfonylureas drugs-inhibit the market glycosidase, agents that improve insulin resistance, etc. However, the side-effects associated with these means, for biguanide medicines have information about lactic acidosis, for medicines on the basis of sulfonylureas include information about hypoglycemia, and inhibitors of glycosidase has information on diarrhea, and therefore at the present time, there are situations when you really need to develop therapeutic agents for diabetes, having a new mechanism of action that is different from the mechanism listed medicines.

It was reported (see non-Patent Document 1)that phlorizin derived glucose of natural origin, inhibits re-absorption of excess glucose in the kidneys by inhibiting the sodium-dependent glucose cotransporter 2 (SGLT2), present on the SI site of the proximal convoluted renal tubules, and promotes the excretion of glucose, thereby reducing blood sugar levels, and since that time have been widely conducted studies of therapeutic agents for diabetes, based on the inhibition of SGLT2.

For example, in Japanese Patent Publication 2000-080041 A (Patent Document 1), International Publication number WO01/068660 (Patent Document 2), WO04/007517 (Patent Document 3), etc. are reported compounds used as the e SGLT2 inhibitors. However, since phlorizin and compounds described in the above Patent applications contain glucose fragment as a common part of their structure that is considered to be a problem for oral administration, these compounds are easily hydrolyzed under the action of glucosidase present in the small intestine or the like, and their pharmacological action quickly terminated. If phlorizin there are reports that the phloretin, the aglycone of phlorizin, strongly inhibits legkodeformiruemyh type conveyor sugar. For example, it was reported adverse effect of reducing intracerebral glucose concentration when injected intravenously phlorizin rats, see, for example, non-Patent Document 2).

Then, in order to prevent such decomposition and improve the absorption attempts have been made to convert such compounds and their prodrugs. When administered prodrug, it is desirable that this prodrug suitable way metabolizability in the body, which is the target, or close to it to convert it to an active connection. However, as in the living organism there are various metabolic enzymes and the difference between individual organisms substantial, in many cases it is difficult to stably obtain the effect of the prodrug. In addition, attempts were made to convert the glycoside bond compounds in plastics technology : turning & the d-carbon bond (see Patent Documents 4 To 8). However, further improvement of the properties needed for medicines, including activity, metabolic stability, etc.

Patent Document 1: Japanese Patent Publication 2000-080041 A

Patent Document 2: international Publication No.WO01/068660, Brochure

Patent Document 3: International Publication No. WO04/007517, Brochure

Patent Document 4: the Patent Publication U.S. 2001/041674 A

Patent Document 5: the Patent Publication U.S. 2002/137903 A

Patent Document 6: International Publication No. WO01/027128, Brochure

Patent Document 7: international Publication No.WO02/083066, Brochure

Patent Document 8: international Publication No.WO0/013118, Brochure

Non-Patent Document 1: J. Clin. Invest., 93, 1037 (1994)

Non-patent Document 2: Stroke, 14, 388 (1983)

Disclosure of invention

The problem solved by the present invention

The purpose of this invention is the provision cyclohexanone derivatives having suitable properties required for medicines.

The aim of the present invention is, in particular, ensuring cyclohexanone derivatives, which have an action aimed at reducing the level of sugar in the blood, and, in addition, possess appropriate properties required for medicines, such as prolon the new action metabolic stability and security.

In addition, the present invention is to provide pharmaceutical compositions that are used for the prevention or treatment of diabetes, such as insulin-dependent diabetes mellitus (diabetes type I) and insulin-independent diabetes mellitus (type II diabetes), diabetic complications, and diseases such as obesity-induced hyperglycemia.

Means for solving problems

In the result of extensive research conducted by the authors of the present invention to solve the above problems, the authors of the present invention found that cyclohexane derivative represented by formula (I), have an excellent effect on the inhibition of SGLT2, which led to the creation of the present invention.

Namely, in accordance with one aspect of the present invention, is provided cyclohexane derivative represented by formula (I):

Formula 1

where

A represents-O-, -CH2- or-NH-;

n is an integer selected from 0 and 1;

R6and R7each independently represents a hydrogen atom or a C1-C6alkyl group;

m is an integer selected from 1-3;

Q is selected from Q1-Q5represented by the following formula:

Faure is ula 2

where

R1, R2, R3, R4and R5each independently selected from a hydrogen atom, hydroxy-group, C1-C6alkyl group which may be substituted by one or more Ra, C1-C6alkoxygroup, which may be substituted by one or more Ra, C7-C14aralkylated, which may be substituted by one or more Rb, and-OC(=O)Rx;

Rx represents a C1-C6alkyl group which may be substituted by one or more Ra, and aryl group which may be substituted by one or more Rb, a heteroaryl group which may be substituted by one or more Rb, C1-C6alkoxygroup, which may be substituted by one or more Ra, or-NReRf,

Ar1represents Allenova group which may be substituted by one or more Rb, or heteroarenes group which may be substituted by one or more Rb, where heteroarenes group may form a condensed ring with an aromatic carbocycle or aromatic heterocycle;

Ar2represents an aryl group which may be substituted by one or more Rb, or heteroaryl group which may be substituted by one or more Rb;

Ra, each independent of the Sabbath., selected from halogen atom, hydroxy-group, ceanography, nitro, carboxypropyl, C1-C6alkoxygroup, which may be substituted by one or more RC, an aryl group which may be substituted by one or more Rd, alloctype, which may be substituted by one or more Rd, a heteroaryl group which may be substituted by one or more Rd, heterokaryosis, which may be substituted by one or more Rd, mercaptopropyl, C1-C6allylthiourea, C1-C6alkylsulfonyl group, C1-C6alkylsulfonyl group, -NRfRg, and C1-C6alkylcarboxylic group which may be substituted by one or more RC;

Rb, each independently selected from C1-C6alkyl group which may be substituted by one or more RC, C1-C6alkenylphenol group which may be substituted by one or more RC, C3-C8cycloalkyl group which may be substituted by one or more RC, C7-C14aranceles group which may be substituted by one or more Rd, halogen atom, hydroxy-group, ceanography, nitro, carboxypropyl, C1-C6alkoxygroup, which may be substituted by one or more RC, an aryl group, which may be zames is on one or more Rd, alloctype, which may be substituted by one or more Rd, a heteroaryl group which may be substituted by one or more Rd, heterokaryosis, which may be substituted by one or more Rd, mercaptopropyl, C1-C6alkylthio, C1-C6alkylsulfonyl group, C1-C6alkylsulfonyl group, -NRfRg, C1-C6alkylcarboxylic group which may be substituted by one or more RC, C1-C3alkylenedioxy, heterocyclyl group, -CO2Ri-CONRiRj;

RC each independently selected from a halogen atom, hydroxy-group, ceanography, nitro, carboxypropyl, C1-C6alkoxygroup, which may be substituted by one or more halogen atoms, aryl group which may be substituted by one or more Rd, alloctype, which may be substituted by one or more Rd, a heteroaryl group which may be substituted by one or more Rd, heterokaryosis, which may be substituted by one or more Rd, an amino group, a C1-C6alkylamino and di(C1-C6alkyl)amino;

Rd each independently selected from C1-C6alkyl group which may be substituted by one or more halogen atoms, C1-C6alkoxygroup to ora may be substituted by one or more halogen atoms, C7-C14aranceles group which may be substituted by one or more halogen atoms, halogen atom, hydroxy-group, ceanography, nitro, amino, C1-C6alkylamino and di(C1-C6alkyl)amino;

Re represents a hydrogen atom, a C1-C6alkyl group which may be substituted by one or more RC, an aryl group which may be substituted by one or more Rd, or heteroaryl group which may be substituted by one or more Rd;

Rf represents a hydrogen atom or a C1-C6alkyl group which may be substituted by one or more RC;

Rg represents a hydrogen atom, a C1-C6alkyl group which may be substituted by one or more RC, C1-C6alkylcarboxylic group which may be substituted by one or more RC, an aryl group which may be substituted by one or more Rd, a heteroaryl group which may be substituted by one or more Rd, karbamoilnuyu group, C1-C6alkoxycarbonyl, which may be substituted by one or more RC, or C1-C6alkylsulfonyl group which may be substituted by one or more RC;

Re and Rf, and Rf and Rg, respectively, together with the nitrogen atom which, with which they are linked, may form a 4-7-membered heterocycle; and

Ri and Rj each independently selected from a hydrogen atom, a C1-C6alkyl group which may be substituted by one or more RC, C3-C8cycloalkyl group which may be substituted by one or more RC, and C7-C14aranceles group which may be substituted by one or more Rd, or its prodrug, or pharmaceutically acceptable salt.

In accordance with another aspect of the present invention is provided cyclohexane derivative represented by formula (I), where n has a value of 1, or its prodrug or pharmaceutically acceptable salt. In this case, A preferably represents-O - or-NH-. In addition, the system of substitution in Ar1preferably represents one in which the Deputy -(CR6R7)m-Ar2associated with the ring atom, which is adjacent to the ring atom bound to the Deputy A. for Example, when Ar1represents fenelonov group, is preferred ortho-substitution, and, for example, when Ar1represents thienylene group, preferred is 2,3-substitution or 3,4-substitution, and, in addition, for example, when Ar1represents pyridinylamino group, preferred is is 2,3-substitution, 3,4-substitution, 4,5-substitution or 5,6-substitution. In addition, when Ar1represents pyrazolidinone group, preferred is 3,4-substitution, 4,5-substitution or 1,5-substitution. Deputy and A Deputy -(CR6R7)m-Ar2can be linked to the ring nitrogen atom.

In accordance with the following aspect of the present invention is provided cyclohexane derivative represented by formula (I), where n is 0, or its prodrug, or pharmaceutically acceptable salt. In this case, the system replacement in Ar1preferably represents one in which the Deputy -(CR6R7)m-Ar2associated with the second ring atom, separated from the ring atom bound to Q. for Example, when Ar1represents fenelonov group, preferred is a meta-substitution, and, for example, when Ar1represents pyridinylamino group, preferred is 2,4-substitution, 3,5-substitution, 4,6-substitution or 1,6-substitution. In addition, when Ar1represents Intellinova group, preferred is 1,3-substitution, 3,4-substitution, 4,6-substitution or 5,7-substitution. In addition, when Ar1represents pyrazolidinone group, preferred is 1,3-substitution, 3,5-substitution or 1,4-substitution. Will replace the l and A Deputy -(CR 6R7)m-Ar2can be linked to the ring nitrogen atom.

In the above-described formula (I), m preferably has a value of 1. In addition, Ar1preferably represents fenelonov group, Neftyanoy group, thienylene group, pyridinylamino group, Intellinova group or pyrazolidinone group, and particularly preferred are fenelonov group, taylena group, peridiniella group and Intellinova group (these groups may be substituted by one or more Rb).

In the above-described formula (I), m preferably has a value of 1, and, in addition, Ar2preferably represents a phenyl group, naftalina group, thienyl group, benzofuranyl group, benzothiazoline group, benzodioxolyl group, 2,3-dihydrobenzofuranyl group or 2,3-dihydrobenzofuranyl group, and particularly preferred are a phenyl group, benzodioxolyl group and 2,3-dihydrobenzofuranyl group (these groups may be substituted by one or more Rb).

In the above-described Q1-Q5preferably, when R1, R2, R3, R4and R5each independently selected from a hydroxy-group, and-OC(=O)Rx.

In accordance with the following aspect of the present invention provides a compound described you the e of the formula (I), where m is 1; n is 1; And a represents-O - or-NH-; Ar1represents fenelonov group, Neftyanoy group, thienylene group, pyridinylamino group, Intellinova group or pyrazolidinone group (these groups may be substituted by one or more Rb); Ar2represents a phenyl group, naftalina group, thienyl group, benzofuranyl group, benzothiazoline group, benzodioxolyl group, 2,3-dihydrobenzofuranyl group or 2,3-dihydrobenzofuranyl group (these groups may be substituted by one or more Rb); and R1, R2, R3, R4and R5each independently selected from a hydroxy-group, and-OC(=O)Rx, or its prodrug, or pharmaceutically acceptable salt.

In accordance with another aspect of the present invention is provided a compound of the above formula (I), where m is 1; n is 0; Ar1represents fenelonov group, Neftyanoy group, thienylene group, pyridinylamino group, Intellinova group or pyrazolidinone group (these groups may be substituted by one or more Rb); Ar2represents a phenyl group, naftalina group, thienyl group, benzofuranyl group, benzothiazoline group, benzodioxolyl group, 2,3-dihydrobenzo the uranyl group or 2,3-dihydrobenzofuranyl group (these groups may be substituted by one or more Rb); and R1, R2, R3, R4and R5each independently selected from a hydroxy-group, and-OC(=O)Rx, or its prodrug, or pharmaceutically acceptable salt.

In accordance with another aspect of the present invention provides a compound selected from the following groups:

[2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[1S,2R,3R,4R,6S]-4-hydroxymethyl-6-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3-triol;

[2-(4-cryptomaterial)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-cyclopentylmethyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-Chlorobenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

(2-benzoylphenyl)-5a-carb-β-D-glucopyranoside;

[2-(4-isopropylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-cyclopropylmethyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-n-propylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-trifloromethyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methylsulfonylbenzoyl)phenyl]-5a-carb-β-D-glucopyranoside;

[3-fluoro-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(3-trifloromethyl)phenyl]-5a-carb-β-D - glucopyranoside;

[2-(4-methoxybenzyl)-4-were]-5a-carb-β-D-glucopyranoside;

[2-(3-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methoxybenzyl)-4-methoxyphenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methoxybenzyl)-6-were]-5a-carb-β-D-glucopyranoside;

[2-(4-methoxybenzyl)-4-forfinal]-5a-carb-β-D-glucopyranoside;

[2-(3-terbisil)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(3-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[5-fluoro-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methylsulfonylbenzoyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-terbisil)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(3,4-dimethoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-active compounds)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-hydroxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-cyanobenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(3-cryptomaterial)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-aminomethylbenzoic)phenyl]-5a-carb-β-D-glucopyranoside;

[5-methoxy-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methoxycarbonylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-carbamoylmethyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-N,N-dimethylcarbamoyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-ethoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-deformational)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-tert-butylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methoxybenzyl)phenyl]-5-triptorelin-3-yl]-5a - carb-β-D-glucopyranoside;

[3-methoxy-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glycophorin the Zid;

[2-(4-methoxybenzyl)-3-were]-5a-carb-β-D-glucopyranoside;

[2-(3-fluoro-4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[4-(4-cyclopropylmethyl)pyridine-3-yl]-5a-carb-β-D-glucopyranoside;

[2-(4-carboxybenzoyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-vinylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

{2-[4-(2,2-defermined)benzyl]phenyl}-5a-carb-β-D-glucopyranoside;

[2-(2,3-dihydrobenzofuran-5-ylmethyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(3-fluoro-4-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methoxy-3-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-(pyrazole-1-ylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(3-chloro-4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(3,4-methylenedioxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-cyclobutylmethyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-acetylphenyl)phenyl]-5a-carb-β-D-glucopyranoside;

[2-(4-methoxybenzyl)-5-were]-5a-carb-β-D-glucopyranoside;

[2-(4-active compounds)thiophene-3-yl]-5a-carb-β-D-glucopyranoside;

[2-(benzothiophen-2-yl)were]-5a-carb-β-D-glucopyranoside;

(R)-{2-[1-(4-cyclopropylmethyl)ethyl]phenyl}-5a-carb-β-D-glucopyranoside;

(S)-{2-[1-(4-cyclopropylmethyl)ethyl]phenyl}-5a-carb-β-D - glucopyranoside;

[2-(4-cyclopropylmethyl)-5-methylthiophene-3-yl]-5a-carb-β-D glucopyranoside;

[2-(4-active compounds)-5-methylthiophene-3-yl]-5a-carb-β-D-glucopyranoside;

[5-chloro-2-(4-cyclopropylmethyl)thiophene-3-yl]-5a-carb-β-D - glucopyranoside;

(1R,2S,3R,6R)-6-[2-(4-cyclopropylmethyl)phenoxy]-4-

(hydroxymethyl)cyclohex-4-ene-1,2,3-triol;

(1R,2S,3R,6R)-4-hydroxymethyl-6-[2-(4-methoxybenzyl)-phenoxy]cyclohex-4-ene-1,2,3-triol;

(1R,2S,3S,6R)-4-[3-(4-active compounds)phenyl]-6-(hydroxy-methyl)cyclohex-4-ene-1,2,3-triol;

(1R,2R,3S,4R,5R)-1-[3-(4-active compounds)-4-methoxyphenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1R,2R,3S,4S,6R)-4-[3-(4-active compounds)-4-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4R,5R)-1-[2-ethoxy-5-(4-active compounds)phenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1R,2R,3S,4S,6R)-4-[2-ethoxy-5-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2,4-dimethoxy-phenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2,4-acid]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-were]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-were]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-methoxyphenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-triptoreline-phenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1R,2R,3S,4S,6R)-4-[5-(4-isopropylbenzyl)-2-methox the phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4S,6R)-4-[3-(4-active compounds)phenyl]-6-(hydroxy-methyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4S,6R)-4-[3-(4-hydroxybenzyl)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-hydroxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4S,6R)-4-[3-(4-cyclopropylmethyl)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-forfinal]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1S,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-forfinal]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;

(1R,2R,3S,4R,5R)-5-hydroxymethyl-1-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3,4-tetraol;

(lS,2R,3S,4R,5R)-5-hydroxymethyl-1-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3,4-tetraol and

(1R,2R,3S,4S,6R)-4-[l-(4-active compounds)-1H-indol-3-yl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol,

or its prodrug or pharmaceutically acceptable salt.

In accordance with another aspect of the present invention is provided a pharmaceutical composition comprising the compound of the above formula (I), which is used as an inhibitor of Na+-glucose cotransporter.

In accordance with another aspect of the present invention is provided a pharmaceutical composition comprising the compound of the above formula (I), which are used for the prevention or treatment of diabetes, such as insulin-dependent diabetes mellitus (diabetes type I and insulin-independent diabetes mellitus (type II diabetes), diabetic complications caused by hyperglycemia, or obesity.

In accordance with the following aspect of the present invention provides a method of prophylaxis or treatment of diabetes, such as insulin-dependent diabetes mellitus (diabetes type I) and insulin-independent diabetes mellitus (type II diabetes), diabetic complications caused by hyperglycemia, and obesity, which includes an introduction to the patient an effective amount of the compound of the above formula (I) or its pharmaceutically acceptable salt.

In the above-described Q1-Q5groups represented by R1, R2, R3, R4and R5may represent, each independently, for example, the hydroxy-group, With1-C6alkyloxy, C7-C14aralkylated or-OC(=O)Rx, and, in particular, preferably, when R1, R2, R3, R4and R5all represent a hydroxy-group.

In the compounds of the present invention, n preferably has a value of 1, and in this case, A preferably represents-O - or-NH -, and particularly preferably represents-O-.

In the above-described formula (I) Ar1and Ar2can be substituted by one to four substituents Rb, and Rb is preferable halogen atom; a hydroxy-group; C1-C6alkyl group and C 3-C8cycloalkyl group which may be substituted by one to four substituents selected from halogen atom, hydroxy-group and amino group; C1-C6alkyloxy and C1-C6allylthiourea, which may be substituted by one to four substituents selected from halogen atom, hydroxy-group and amino; cyano; C1-C6alkylsulfonyl group; a nitro-group; carboxypropyl; -NReRf where Re represents a hydrogen atom, a C1-C6alkyl group, a C1-C6alkylcarboxylic group, carbamoyl group1-C6alkylsulfonyl group or1-C6alkoxycarbonyl group, and Rf represents a hydrogen atom or a C1-C6alkyl group); a 5 - or 6-membered heteroaryl group; or a 4 - to 6-membered heterocyclyl group.

Of the groups represented by Ar1, Allenova group is a divalent group consisting of aromatic carbocycle, preferably, aromatic carbocycle containing 6-10 carbon atoms, and includes, for example, fenelonov group and Neftyanoy group. Heteroarenes group is a divalent group comprising an aromatic heterocycle, preferably, 6-10-membered aromatic heterocycle, and includes, for example, Goethe is Allenova group, containing pyrrole ring, indole ring, thiophene ring, benzothiophene group, furan ring, benzopyrrole ring, pyridine ring, quinoline ring, isoquinoline group, a thiazole ring, benzothiazoline ring, isothiazol ring, benzothiazoline ring, pyrazol ring, indazol ring, oxazoline ring, benzoxazole ring, isoxazole ring, benzisoxazole ring, imidazole ring, benzoimidazole ring, triazole ring, benzotryazolyl ring, pyrimidine ring, originoo ring, pyrazinone ring or pyridazinone ring. As Ar1preferred, in particular, are fenelonov group, naftalanovaja group and heteroarenes group containing pyridine ring, pyrrole ring, indole ring, thiophene ring, benzothiophene ring, furan ring, benzopyrrole ring or pyrazol ring, and more preferred are fenelonov group, taylena group, peridiniella group and Andrianova group.

Of the groups represented by Ar2, aryl group is a phenyl group, naftalina group or azulinebloo group, and heteroaryl group is pyrrolidinyl group, indolenine group, pyridyloxy group, pinolillo group, itchino the ilen group, thienyl group, benzothiazoline group, follow group, benzofuranyl group, thiazolidine group, benzothiazolyl group, isothiazolinone group, benzothiazolyl group, pyrazolidine group, indazolinone group, oxazolidinyl group, benzoxazolyl group, isoxazolyl group, benzisoxazole group, imidazolidinyl group, benzimidazolyl group, triazolyl group, benzotriazolyl group, pyrimidinyl group, brazilrio group, personilnya group, pyridazinyl group or the like, and as Ar2preferred is a phenyl group, naftalina group, thienyl group, benzothiazoline group, benzodioxolyl group, furilla group, benzofuranyl group or 2,3-dihydrobenzofuranyl group, and more preferred is a phenyl group, benzodioxolyl group or 2,3-dihydrobenzofuranyl group.

The term "C1-C6alkyl group"as used in this application, means a linear or branched alkyl group containing from 1 to 6 carbon atoms, and includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 3-methylbutyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3-etival the l and 2-ethylbutyl, and preferred1-C6alkyl groups include, for example, linear or branched alkyl groups containing from one to three carbon atoms, and particularly preferred are methyl and ethyl.

The term “C3-C8cycloalkyl group", as used in this application, means a cyclic alkyl group containing 3 to 8 carbon atoms, and includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

The term "C1-C6alkoxygroup as used in this application means alkyloxy containing linear or branched alkyl group containing from 1 to 6 carbon atoms as the alkyl fragment, and includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, n-pentox, 3 methylbutoxy, 2-methylbutoxy, 1 methylbutoxy, 1 ethylpropoxy, n-hexyloxy, 4-methylphenoxy, 3 methylpentane, 2-methylpentane, 1 methylphenoxy and 3 ethylbutane.

The term "aryl group"as used in this application, means an aryl group containing an aromatic hydrocarbon ring containing from 6 to 10 carbon atoms, and includes, for example, phenyl, 1-naphthyl and 2-naphthyl.

The term "C7-C14kalkilya group", as used in Toyama application means arylalkyl group containing from 7 to 14 carbon atoms and containing defined above aryl group and includes, for example, benzyl, 1-phenethyl, 2-phenethyl, 1-naphthylmethyl and 2-naphthylmethyl.

The term "C7-C14arancelaria as used in this application means arylalkylamine containing from 7 to 14 carbon atoms and containing defined above aracelio group, and includes, for example, benzyloxy, 1-penetrate, 2-penetrate, 1 naphthalenyloxy and 2 naphthalenyloxy.

The term "heteroaryl group"as used in this application means a 5-10 membered aromatic heterocyclyl group containing one or more heteroatoms independently selected from oxygen atom, nitrogen atom and sulfur atom, and includes, for example, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, chinoline and ethenolysis. Preferred heteroaryl groups are 5-6 - membered heteroaryl group, such as pyrrolidine group, pyrazolidine group, imidazolidinyl group and Peregrina group, and particularly preferred is pyrazolidine group.

The term "alloctype"as used in this Declaration, the ke, means alloctype containing defined above aromatic hydrocarbon group containing from 6 to 10 carbon atoms, as the aryl fragment, and includes, for example, phenoxy, 1 naphthoxy and 2 naphthoxy.

The term "heteroanalogues as used in this application means heteroepitaxy containing defined above 5-10-membered aromatic heterocyclyl group that contains one or more heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom, as heteroaryl fragment, and includes, for example, forelocks, titilate, pyrrolidone, imidazolidine, pyrazolinone, oxazolidone, isoxazolidine, thiazolidine, isothiazolinone, oxadiazolidine, thiadiazolidine, triazolinone, tetrazolate, pyridyloxy, pyrimidinone, pyrazinone, pyridazinone, intolerance, hyalinelike, ethanolinduced. The preferred heteroarylboronic are 5-6-membered heterokaryosis.

The term "C1-C6alkylamino as used in this application means alkylamino containing linear or branched alkyl group containing from 1 to 6 carbon atoms as the alkyl fragment, and includes, for example, methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, sec-b is thylamino, isobutylamino, tert-butylamino, n-pentylamine, 3 methylbutylamine, 2-methylbutylamine, 1 methylbutylamine, 1 ethylpropylamine, n-hexylamino, 4-methylpentylamino, 3 methylpentylamino, 2-methylpentylamino, 1 methylpentylamino, 3 ethylbutylamine and 2 ethylbutylamine.

The term "di(C1-C6alkyl)amino group"as used in this application means dialkylamino containing linear or branched alkyl group containing from 1 to 6 carbon atoms in the two alkyl fragments, which may be the same or different from each other. "Di(C1-C6alkyl)amino group" includes, for example, dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, di-n-butylamino, methyl-n-butylamino, methyl-sec-butylamine, methylisobutylketone, tert-butylamino, ethyl-n-butylamino, ethyl-sec-butylamino, ethylisopropylamine and ethyl-tert-butylamino.

The term "C1-C6allylthiourea as used in this application means allylthiourea containing linear or branched alkyl group containing from 1 to 6 carbon atoms as the alkyl fragment, and includes, for example, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, sec-butylthio, isobutyric, tert-butylthio, n-pentylthio, 3 methylbutyl, 2-methylbutyl, 1 methylbutyl, 1 ethylpropyl n-hexylthio, 4 methylphenylthio, 3 methylphenylthio, 2-methylphenylthio, 1 methylphenylthio, 3 ethylbutyl and 2 ethylbutyl.

The term “C1-C6alkylsulfonyl group", as used in this application means alkylsulfonyl group (-SO-R), containing a linear or branched alkyl group containing from 1 to 6 carbon atoms as the alkyl fragment, and includes, for example, methylsulfinyl, ethylsulfinyl, n-propylsulfonyl, isopropylphenyl, n-butylsulfonyl, second-butylsulfonyl, isobutylamine, tert-butylsulfonyl, n-pentylaniline, 3-methylbutylamine, 2-methylbutylamine, 1-methylbutylamine, 1-ethylpropylamine, n-hexylaniline, 4-methylphenylsulfonyl, 3-methylphenylsulfonyl, 2-methylphenylsulfonyl, 1-methylphenylsulfonyl, 3-ethylbutylamine and 2-ethylbutylamine.

The term "C1-C6alkylsulfonyl group", as used in this application means alkylsulfonyl group containing a linear or branched alkyl group containing from 1 to 6 carbon atoms as the alkyl fragment, and includes, for example, methylsulphonyl, ethylsulfonyl, n-propylsulfonyl, isopropylphenyl, n-butylsulfonyl, second-butylsulfonyl, isobutylamine, tert-butylsulfonyl, n-peterculter, 3-methylbutylamine, 2-methylbutylamine is l, 1-methylbutylamine, 1-ethylpropylamine, n-hexylsilane, 4-methylphenylsulfonyl, 3-methylphenylsulfonyl, 2-methylphenylsulfonyl, 1-methylphenylsulfonyl, 3-ethylbutylamine and 2-ethylbutylamine.

The group-OC(=O)-Rx," as used in this application includes, for example, With1-C6alkylcarboxylic, C7-C14aralkylamines,1-C6alkoxycarbonylmethyl and C7-C14uralelectropech.ru. In this case, the1-C6alkylcarboxylic includes, for example, acetyloxy, propionyloxy, utilicorp and pivaloyloxy, and particularly preferred is acetyloxy. C7-C14arylchlorosilanes includes, for example, benicarbenicar and naphthylethylenediamine, and preferred is benicarbenicar.

With1-C6alkoxycarbonylmethyl includes, for example, methoxycarbonylamino and ethoxycarbonylmethoxy, and preferred is methoxycarbonylamino. C7-C14aracelikarsaalyna includes, for example, benzyloxycarbonyloxy and naphthylethylenediamine, and preferred is benzyloxycarbonyloxy.

The term "halogen atom", as used in this the soup of the application includes, for example, fluorine atom, chlorine atom, bromine atom and iodine atom.

The term "4-7-membered heterocycle", as used in this application, means a heterocycle, which may be fully saturated or partially or fully unsaturated and contains one nitrogen atom and may further contain one or more heteroatoms independently selected from oxygen atom, nitrogen atom and sulfur atom, and includes, for example, azetidine, pyrrolidine, piperidine and morpholine, and is preferred piperidine.

The term "aromatic carbocycle as used in this application means 6-10-membered aromatic carbocycle and includes, for example, benzene ring and naphthalene ring.

The term "aromatic heterocycle", as used in this application means a 5-6-membered aromatic heterocycle containing one or more heteroatoms independently selected from oxygen atom, nitrogen atom and sulfur atom, and includes, for example, pyrrole ring, indole ring, thiophene ring, benzothiophene ring, furan ring, benzopyrrole ring, pyridine ring, quinoline ring, isoquinoline ring, a thiazole ring, benzothiazoline ring, isothiazol ring, benzothiazoline ring, pyrazol ring, indazol ring, oxazoline ring, benzoxazole number of the TSO, isoxazoline ring, benzisoxazole ring, imidazole ring, benzoimidazole ring, triazole ring, benzotryazolyl ring, pyrimidine ring, Aracinovo ring, pyrazinone ring and pyridazinone ring.

The term "heterocyclyl group", as used in this application means a 4-7-membered heterocyclyl group that contains one or more heteroatoms independently selected from oxygen atom, nitrogen atom and sulfur atom, and may be fully saturated or partially or fully unsaturated and comprises, for example, azetidine, pyrrolidine, piperidinyl, piperazinil, pyrrolyl, imidazolyl, imidazolyl, pyrazolyl, pyrazolyl, oxazolyl, morpholinyl, thiomorpholine, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, hexamethylenimine, furyl, tetrahydrofuryl, thienyl, tetrahydrofuryl, DIOXOLANYL, and oxathiolanes dioxane. The position of substitution in heterocyclyl group is not specifically limited, provided that it represents a substitutable position on carbon atom or nitrogen atom.

The term "C1-C3alkylenedioxy"as used in this application, means a divalent group represented by the formula: -O-(C1-C3alkylene)-O-and include, for example, methylenedioxy, Ethylenedioxy and dimethylmethylene the group.

In addition, the compounds of the present invention include mixtures of different types of tautomers, stereoisomers such as optical isomers and their selected isomers.

Compounds of the present invention may form an acid additive salt. In addition, depending on the type of substituent, they can form salts with bases. Such salts include, for example, acid additive salts of inorganic acids such as hydrochloric acid, Hydrobromic acid, itestosterone acid, sulfuric acid, nitric acid and phosphoric acid; organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonate acid and econsultancy acid; amino acid type, such as aspartic acid and glutamic acid. In addition, salts formed with bases include salts with inorganic bases, such as salts of sodium, potassium, magnesium, calcium and aluminium, salts with organic bases such as methylamine, ethylamine, and ethanolamine; salts with amino acids basic type, such as lysine and ornithine; and ammonium salts.

In addition, the compounds of the present is ademu the invention include hydrates and various pharmaceutically acceptable solvate, polymorphs, etc.

In addition, the compounds of the present invention is not limited to the compounds described in the Examples below, and include all of the cyclohexane derivative represented by the above formula (I)and their pharmaceutically acceptable salts.

In addition, the present invention includes compounds which are converted into compounds represented by the above formula (I), as a result of metabolism in vivo, and their pharmaceutically acceptable salts, i.e. the so-called “prodrugs”. Groups that form the prodrugs of the compounds of the present invention, include, for example, the groups described in Prog. Med., 5, 2157-2161(1985), and groups described in the Development of Drugs (Molecular Designing) 7, 163-198, Hirokawa Shoten, 1990.

Compounds of the present invention can be obtained by using various known synthesis methods, depending on their distinctive characteristics, based on the type of their main skeleton or Deputy. In the case when the group is, preferably, is replaced by a suitable protecting group at the stage of the source materials or intermediate compounds, from a technological point of view, such a protective group can be removed at a later stage to give the desired compound. Groups that require protection during the stage of producing compounds include, for example, the R, the hydroxy-group and carboxypropyl, and protective groups for these groups include the protective groups described in Greene and Wuts: Protective Groups in Organic Synthesis, 2nd ed. Used protective group and the reaction conditions for the introduction and removal of protective groups appropriately chosen based on known methods such as described in the above documents.

Compounds of the present invention have the activity of inhibiting the sodium-dependent glucose Transporter 2 (SGLT2) (J. Clin. Invest., 93, 397(1994)), related to renal reabsorption of glucose. By inhibiting SGLT2 the reabsorption of glucose is reduced, excess glucose is excreted and hyperglycemia cured, without creating a burden on the β-cells of the pancreas, providing a therapeutic effect against diabetes and the effect of improvement in the treatment of insulin resistance.

Thus, in accordance with one aspect of the present invention provides a drug for the prophylaxis or treatment of a disease or condition which can be improved by inhibiting SGLT2 activity, such as diabetes, diabetes-related diseases and diabetic complications.

The term "diabetes"as used in this application, includes diabetes type I, diabetes type II and other types of diabetes, called specifices what their reasons. In addition, the term "diabetes-related disease"as used in this application includes, for example, obesity, hyperinsulinemia, impaired sugar metabolism, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, lipid metabolism disorders, hypertension, congestive heart failure, edema, hyperuricemia and gout.

In addition, the term "diabetic complications", as used in this application includes both acute complications and chronic complications. Acute complications include, for example, hyperglycemia (ketoacidosis, etc.) and infectious diseases (e.g., skin, soft tissue, biliary tract, respiratory system and urinary tract), and "chronic complications include, for example, the microangiopathy (nephropathy and retinopathy), arteriosclerosis (e.g., atherosclerosis, myocardial infarction, cerebral thrombosis and thrombosis of arteries of lower Konechnaya), neuropathy (e.g., sensory nerve, motor nerve and beam autonomic nerve fibers) and gangrene of the foot. Main complications of diabetes include, for example, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy.

In addition, the compounds of the present invention can be used in combination with treatment for diabetes, treatment for diabetes, Oslo the response treatment for hyperlipidemia, treatment for hypertension or the like, mechanism of action which is distinct from the mechanism of action of inhibitors of SGLT2 activity. When combining compounds of the present invention with other means you can expect more effect compared with the effect obtained when using each tool separately for the treatment of the above diseases.

"Tools for the treatment of diabetes and tools for the treatment of diabetic complications", which is used in combination include, for example, tools that enhance insulin sensitivity (such as an agonist of PPAR γ agonist PPAR α/γ agonist of PPAR-δ and PPAR agonist α/γ/δ), glycosidase inhibitors, biguanide medicines, tools, stimulating insulin secretion, insulin receptor antagonists of glucagon, a tool to stimulate the kinase of the insulin receptor inhibitors tripeptidylpeptidase II inhibitors dipeptidylpeptidase IV inhibitors proteinkinases phosphatase-1B inhibitors, glycogen phosphorylase inhibitors glucose-6-phosphatase, inhibitors of gluconeogenesis, inhibitors bisphosphatase fructose, inhibitors piruvatdegidrogenazy, activators of glucokinase, D-Hiro-Inositol, inhibitors of kinase 3 synthesis of glycogen, glucagon-like peptide 1 analogues of glucagon-like peptide-1, AGON the texts glucagon-like peptide-1, amirin, the analogues of amerina, agonists of amerina, glucocorticoid receptor antagonists, inhibitors of 11β-hydroxysteroid-dehydrogenase inhibitors aldozoreduktaza, inhibitors of protein kinase C antagonists of the receptor γ-aminobutyric acid, sodium channel antagonists, inhibitors of transcription factor NF-kB inhibitors of IKK-β inhibitors of lipids-peroxidase inhibitors N-acetylated-α-linked-acid-dipeptidase, insulin-like growth factor-I, platelet-derived growth factor (PDGF), analogues of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), nerve growth factor, a carnitine derivatives, uridine, 5-hydroxy-1-methylhydantoin, EGB-761, vimolmal, sulodexide, Y-128, and TAR-428.

As a means for treating diabetes and for the treatment of diabetic complications for illustration are the following tools.

"Biguanide drugs" include, for example, Metformin hydrochloride, phenformin.

From "means of stimulating insulin secretion" means on the basis of sulfonylureas include, for example, gliburid (glibenclamide), glipizide, gliclazide and hlorpropamid and desulfonylation tools include, for example, nateglinide, Repaglinide and mitiglinide.

"Insulin" includes recombinant human insulin and insulin of animal origin and are divided into three gr is PPI depending on the time steps, namely type immediate action (human insulin and human neutral insulin), medium type (aqueous suspension of insulin-human asianovela insulin aqueous suspension of human neutral insulin-human asianovela insulin aqueous suspension of human zinc insulin and a water suspension of zinc-insulin) and type of prolonged action (suspension of the human crystalline zinc insulin).

"Glycosidase inhibitors" include, for example, acarbose, voglibose and miglitol.

Agonists of PPAR γ, related to the "tools that enhance insulin sensitivity include, for example, troglitazone, pioglitazone and rosiglitazone, and the double-acting agonists of PPAR α/γ include, for example, MK-767 (KRP-297), tesaglitazar, LM-4156, LY 510929, DRF-4823 and TY-51501, and agonists of PPAR δ include, for example, GW-501516.

"Inhibitors tripeptidylpeptidase II include, for example, UCL-139.

"Inhibitors dipeptidylpeptidase IV include, for example, NVP-DPP728A, LAF-237, MK-0431, P32/98 and TSL-225.

"Inhibitors aldozoreduktaza" include, for example, ascorbyl galement, tolrestat, epalrestat, fidarestat, sorbinil, ponalrestat, resurected and zenarestat.

"Antagonists of the receptor γ-aminobutyric acid" includes, for example, topiramate.

"Sodium channel antagonists include, for example, meksiletin hydrochloride.

"Inhibitors of factor tra is scriptie NF-KB include, for example, dukkipati.

"Inhibitors lipoperoxides" include, for example, tirilazad mesilate.

"Inhibitors of N-acetylated-α-linked-acid-dipeptidase" include, for example, GPI-5693.

"Derivatives of carnitine include, for example, carnitine and levaquin hydrochloride.

"Tools for the treatment of hyperlipidemia and means for the treatment of hypertension", which can be used in combination include, for example, inhibitors of coenzyme hydroxymethylglutaryl, fibrate compounds, agonists β3-adrenaline receptor, AMPK activators, inhibitors of acyl-coenzyme a: cholesterylester, probucol, agonists of the receptor for thyroid hormone, inhibitors of cholesterol absorption, lipase inhibitors, inhibitors of protein transfer of triglycerides in microsomes, lipoxygenase inhibitors, inhibitors carnitinelongevity inhibitors stvalentines, activators of receptor low-density lipoprotein, derivatives of nicotinic acid, bile acid adsorbents, inhibitors conjugated with sodium Transporter of bile acids, inhibitors of protein migration of ester cholesterol, inhibitors of angiotensin-converting enzyme, receptor antagonists angiotensin II inhibitors of endothelin-converting enzyme, receptor antagonists endothelin, diuretics, calcium antagonists is, vasodilator antihypertensives, blockers, acting on the sympathetic nervous system, antihypertensives Central action, agonists α2-adrenergic receptor, protivotromboznoe tools, inhibitors of the formation of uric acid, stimulants excretion of uric acid, a means of alkalizing urine means of reducing appetite, agonists of the receptor, adiponectin, GPR40 agonists and antagonists GPR40.

As means for treatment of hyperlipemia and means for the treatment of hypertension for illustration are the following tools.

"Inhibitors of coenzyme hydroxymethylglutaryl" include, for example, fluvastatin, lovastatin, pravastatin, tseriwastatina and pitavastatin.

"Fibrate compounds include, for example, bezafibrat, beclobrate and benefibre.

"Inhibitors stvalentines" include, for example, TAK-475, α-phosphosulfate derivatives (described in U.S. Patent No. 5712396).

"Inhibitors of acyl-coenzyme a: cholesterylester" include, for example, CI-1011, NTE-122, FCE-27677, RP 73163, MCC-147 and DPU-129.

"Activators of receptor low-density lipoprotein" include, for example, MD-700, and LY-295427.

"Inhibitors of protein transfer of triglycerides in the microsomes (MTP inhibitors)include, for example, compounds described in U.S. Patent No. 5739135, 5712279, 5760246 etc.

"Means of reducing and the petite include, for example, agonists epinephrine-norepinephrine (mazindol, ephedrine, etc.), agonists of serotonin (selective inhibitors of reuptake of serotonin, such as fluvoxamine), agonists adrenaline-serotonin (sibutramine etc.), agonists of the receptor melanocortin 4 (MC4R) and α-melanocyte-concentrating hormone (α-MCH), leptin, cocaine - and amphetamine-regulated transcript (CART), etc.

"Agonists of the receptor thyroid hormone include, for example, liotironin sodium and levothyroxine sodium.

"Adsorption inhibitors of cholesterol include, for example, ezetimibe.

"Lipase inhibitors include, for example, orlistat.

"Inhibitors carnitinelongevity" include, for example, etomoxir.

"Derivatives of nicotinic acid include, for example, nicotinic acid, nicotinamide, nicomol and nicorandil.

"Bile acid adsorbents include, for example, cholestyramine, colestilan and colesevelam hydrochloride.

"Inhibitors of angiotensin-converting enzyme include, for example, captopril, enalapril of maleinate, alacepril and cilazapril.

"Receptor antagonists angiotensin II include, for example, the candesartan cilexetil, losartan potassium, eprosartan mesilate.

"Inhibitors of endothelin-converting enzyme include, for example, CGS-31447 and CGS-35066.

"Antagonists of endothelin receptor include, for example, 1-749805, TBC-3214 and BMS-82874.

For example, in the treatment of diabetes, etc. is appropriate when the compounds of the present invention used in conjunction with one or more means selected from the group including tools that enhance insulin sensitivity (agonists of PPAR γ agonists, PPAR α/γ agonists, PPAR δ agonists, PPAR α/γ/δ and so on), glycosidase inhibitors, biguanide medicines, tools, stimulating insulin secretion, insulin and inhibitors dipeptidylpeptidase IV.

In addition, is suitable when the compounds of the present invention used in conjunction with one or more means selected from the group comprising inhibitors of coenzyme hydroxymethylglutaryl, fibrate compounds, inhibitors stvalentines, inhibitors of acyl coenzyme A: cholesterylester, activators of receptor low-density lipoprotein, inhibitors of protein transfer of triglycerides in microsomes and means of reducing the appetite.

Medicines according to the present invention it is possible to enter systemically or by local injection, or oral, or parenteral, for example, rectal, subcutaneous, intramuscular, intravenous or percutaneous route.

Compounds of the present invention, which are used as medicines, can be in any form: in the firmness of the DOI composition, liquid compositions and other compositions, and the most suitable choice carry out as necessary. Medicines according to the present invention can be obtained by including a pharmaceutically acceptable carrier in connection with the present invention. In particular, excipient, filler, binder, baking powder, agent coating, sugar coating, the pH Adjuster or solubilizers tool that is traditionally used, or aqueous or non-aqueous solvent is added to the compounds of the present invention to obtain tablets, pills, capsules, granules, spray powders, powders, liquids and solutions, emulsions, suspensions, injectables or the like by conventional methods used for formulating pharmaceutical compositions. Excipients and fillers include, for example, lactose, magnesium stearate, starch, talc, gelatin, agar, pectin, Arabic gum, olive oil, sesame oil, cacao butter, ethylene glycol and other substances that are usually used.

In addition, the compounds of the present invention can be formulated in the composition by formation of a clathrate compounds with α-, β - or γ-cyclodextrin or methylated-cyclodextrin.

The dose of the compounds of the present invention varies depending on the disease, is Aresti disease, weight, age, sex and route of administration and, preferably, it ranges from 0.1 to 1000 mg/kg body weight/day, more preferably from 10 to 200 mg/kg body weight/day, and you can enter once a day or divided doses several times per day.

Compounds of the present invention can be synthesized, for example, using the methods of preparation, are shown in the following Schemes. "Bn" the following Diagrams indicates benzyl group.

2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (IV), the key intermediate compound can be obtained, for example, in the following way.

Scheme 1

Formula 3

First, after protection of the primary hydroxy-group D-glucola (for example, protection tert-butyl-dimethylsilane group), two secondary hydroxy-group protect using benzyl groups, and then the protective group of the primary hydroxy-group is removed (for example, when the protective group is a tert-butyldimethylsilyloxy group, it is removed using tetrabutylammonium) and, thus, synthesize 3,4-di-O-benzyl-D-glucal (II).

Then the compound (II) can be converted, in five stages, 3,4,6-tri-O-benzyl-5a-carb-D-glucopyranose (III) [Chem. Commun., p.925 (1998)].

The compound (III) can be converted in two stages, 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (IV) [Liebigs. Ann. Chemi., p.267 (1995)].

The compound (V) can be obtained by the method described in document [J. Chem. Soc. Perkin Trans. 1, 3287 (1991)]. In addition, as shown in the following Scheme 2, the compound (V) can also be obtained from compound (IV) with a suitable oxidizing agent (e.g., activated DMSO in the way Swern or PCC, PDC, peridinin dessa-Martin or similar)

Scheme 2

Formula 4

The compound (IV) can be converted to compound (VII), as shown below.

Scheme 3

Formula 5

The compound (IV) can be converted into 2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranose (VI), for example, by performing hydrolysis after the reaction, Mitsunobu with benzoic acid.

Then the compound (VII)in which X represents a halogen atom, can be obtained by providing exposure to a suitable halogenation agent such as phosphorus oxychloride, oxybromide phosphorus, trichloride phosphorus, tribromide phosphorus, carbon tetrachloride-triphenylphosphine, tetrabromide carbon-triphenylphosphine, N-chlorosuccinimide-triphenylphosphine, N-bromosuccinimide-triphenylphosphine, iodine-triphenylphosphine or the like) to the compound (VI).

Then the compound (VII)in which X represents methanesulfonamido, p-toluensulfonate, triftormetilfullerenov or the like, can be obtained, provided the th impact of methanesulfonanilide, p-toluensulfonate, anhydrous triftormetilfullerenov acid or the like, to the compound (IV) in a suitable solvent under alkaline conditions.

For example, the compound of the following formula:

Formula 6

where R11has the same meaning as indicated above for the Rb; and Ar2has the above value, which is an intermediate compound of the compounds of formula (I)can be synthesized with reference to the following documents: International Publication number WO01/68660, WO01/074834, WO01/074835, WO02/28872, WO02/44192, WO02/064606, WO03/011880 and WO04/014931.

For example, the following connections:

Formula 7

where R12has the same meaning as indicated above for the Rb; and Ar2has the above value, which are intermediate compounds of the compounds of formula (I)can be synthesized with reference to the following document: international Publication No. WO04/007517.

For example, the following connection:

Formula 8

where R13has the same meaning as indicated above for the Rb; and Ar2has the above value, which is an intermediate compound of the compounds of formula (I)can be synthesized with reference to the following documents: International Publication number WO01/16147, WO02/36602, WO02/053573, WO02/068439, WO02/068440, WO02/088157, WO02/098893, WO03/I WO03/090783.

For example, the following connection:

Formula 9

where X1X2X3and X4each represents a nitrogen atom or C-R14and one or two of X1X2X3and X4represent a nitrogen atom; and R14has the same meaning as indicated above for the Rb, which is an intermediate compound of the compounds of formula (I)can be synthesized with reference to the following document: international Publication number WO03/000712.

For example, the following connection:

Formula 10

where R15has the same meaning as indicated above for the Rb; and Ar2has the above value, which is an intermediate compound of the compounds of formula (I)can be obtained according to the following Scheme 4.

Scheme 4

Formula 11

where R1has the same meaning as indicated above for Rb; M-alkyl and M-aryl, each represents an ORGANOMETALLIC reagent, such as n-utility, finality and phenylmagnesium; X represents a halogen, such as chlorine, bromine and iodine; and Ar2has the above value.

Namely, the compound (XIII) can be synthesized by providing exposure to a suitable ORGANOMETALLIC reagent (n-utility, finality, feilman bromide or the like) to the compound (XIV), with the subsequent interaction of the compounds with Ar2-CHO for converting the compound (XV), and implementation after appropriate response recovery (catalytic hydrogenation using a palladium catalyst or the like).

Compounds of the present invention can be obtained, for example, in accordance with Scheme 5, as shown below.

Scheme 5

Formula 12

where R11has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely, the compound of the present invention can be obtained by condensation of the compound (IV) with compound (VIII) under the reaction conditions, Mitsunobu using atragene and phosphine, thus making the removal of protection under conditions of catalytic hydrogenation using a palladium catalyst or the like, or by the removal of protection by means of boron TRIFLUORIDE-dimethyl sulfide or other Atragene that can be used in the synthesis of compounds of the present invention, include, for example, diethylazodicarboxylate, tetramethyldisiloxane and 1,6-dimethyl-1,5,7-hexahydro-1,4,6,7-terazosin-2,5-dione, and phosphines include, for example, triphenylphosphine, tributylphosphine, 2-(dicyclohexylphosphino)biphenyl and three(tert-butyl)phosphine. In addition, the compounds according to the present from which retenu also can be synthesized using the reactions Mitsunobu using postremoval reagent. Fosfornoy reagent that can be used in this case includes, for example, (cyanomethylene)tributylphosphate and (cyanomethylene) trimethylphosphate. In addition, the substituent R11in the compound (XVII) or Vice Ar2(halogen or hydroxy-group after conversion to triflate or the like) can also be converted using a tin-containing reagent, boric acid or the like, in the presence of palladium catalyst.

In addition, the compounds of the present invention can also be obtained, for example, in accordance with Scheme 6, as shown below.

Scheme 6

Formula 13

where X is a halogen, such as chlorine, bromine and iodine, or delete a group such as methanesulfonate and triftorbyenzola; R11has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely, the compound (XVI) can be obtained by condensation of compound (VII) with compound (VIII) in a suitable solvent under alkaline conditions. Bases that can be used in this case include, for example, sodium hydride, potassium carbonate and tert-piperonyl potassium.

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 7, as shown below.

Scheme 7

Formula 14

where R11has the same meaning as indicated above for Rb; R represents a C1-C6alkyl group, a C7-C14aracelio group or aryl group, and Ar2has the above value.

Namely, the compound (XVII) according to the present invention can be obtained by condensation of the compound (IV) with compound (XVIII) under the reaction conditions, Mitsunobu using atragene and phosphine, then convert alkoxycarbonyl group of the compounds obtained in the formyl group in the traditional way of obtaining compound (XX), then providing the impact Ar2-M (where M represents lithium, manygaloherez or the like) to the compound (XX) is converted into compound (XXI), followed by removal of the hydroxy-group and benzyl groups at the same time under conditions of catalytic hydrogenation or sequential removal by restoring the hydroxy-group using trimethylsilane or the like, and then remove the benzyl groups by means of boron TRIFLUORIDE-dimethyl sulfide.

In addition, the compounds of the present invention can also be obtained, for example, in accordance with Scheme 8, as shown below.

Scheme 8

Formula 15

where X11represents a halogen atom; R11has the same meaning as indicated above for the Rb and Ar 2has the above value.

Namely, the compound (XXI) can be synthesized by converting the compound (IV) and the compound (XXII) in the compound (XXIII) by means of the reaction of Mitsunobu, providing then the impact of the ORGANOMETALLIC reagent (lower alkylate, such as n-utility or the like) to the compound (XXIII) to interact with Ar2-CHO.

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 9, as shown below.

Scheme 9

Formula 16

where X21and X22each represents a halogen atom; R" is independently selected from C1-C6alkyl group; R11has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely provide impact connection hexalingual on the compound (XXIII) in the presence of palladium catalyst to convert the compound (XXIV), which then interacts with Ar2-CH2X22in the presence of palladium catalyst to synthesize compound (XVI). Connection hexalingual, as it is used in this application includes, for example, hexamethyldisilane and hexabutylditin and palladium catalyst includes, for example, tetranitropentaerithrite (0) and 1,2-bis(diphenylphosphoryl is ethane)dichloropalladium (II).

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 10, as shown below.

Scheme 10

Formula 17

where R12has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely, the compound (IV) is subjected to condensation with the compound (IX) under the reaction conditions, Mitsunobu using atragene and phosphine for converting the compound (XXV) and then simultaneously carry out the restoration of the ketone and the removal of benzyl groups in the conditions of catalytic hydrogenation using a palladium catalyst or the like, or Paladino carry out the recovery of the ketone with sodium borohydride or the like, and then removing the benzyl group using a palladium catalyst to obtain the compound (XXVI) of the present invention.

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 11, as shown below.

Scheme 11

Formula 18

where R12has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely, the compound (IV) is subjected to condensation with the compound (X) under the reaction conditions, Mitsunobu using Azariah the NTA and phosphine for converting the compound (XXVII), and then provide impact Ar2-M (where M represents lithium, manygaloherez or the like) to the compound (XXVII) to convert it to the compound (XXVIII), then simultaneously or Paladino carry out the removal of the hydroxy-group and benzyl groups under conditions of catalytic hydrogenation using a palladium catalyst or the like to obtain compound (XXVI) of the present invention.

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 12, as shown below.

Scheme 12

Formula 19

where X5has the above meaning; R13has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely, the compound (XXX) according to the present invention can be obtained by reacting compound (VII) with compound (XI) in a suitable solvent, in the presence of a base, to convert the compound (XXIX) with implementation after the removal of benzyl groups in the conditions of catalytic hydrogenation using a palladium catalyst or the like, to give the desired compound.

In addition, in the production method, shown in Scheme 10, the compound (XXXI) (where X1X2X3and X4and Ar2have the above meaning) the present invention can be synthesized by using the compound (XII) instead of compound (IX).

Formula 20

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 13, as shown below.

Scheme 13

Formula 21

where X represents a halogen atom; R17has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely, the compound (XXXV) according to the present invention can be obtained by subjecting the compound (IV) reaction of Mitsunobu with phthalimido, providing processing of the obtained compound with hydrazine or methylamine to obtain the compound (XXXII), then carrying out the reaction mix with compound (XXXIII) in the presence of palladium catalyst [e.g. Tris(dibenzylideneacetone)diplegia (0) or 1,1'-bis(diphenylphosphinomethyl)dichloropalladium (II)] or reagent copper-based [e.g., copper iodide (I)] the conversion of compound (XXXII) in the compound (XXXIV) with subsequent removing benzyl groups under conditions of catalytic hydrogenation using a palladium catalyst or the like

In addition, the compound (XXXII) can be synthesized by implementing the response of Mitsunobu of the compound (IV) with sodium azide or the like, followed by treatment of the compounds with triphenylphosphine or the like

In addition, compound (XXXIII) can be obtained which according to Scheme 14, providing exposure to Ar2-M in the compound (XXXVI), to convert the compound (XXXVII) with subsequent treatment of the compound (XXXVII) triethylsilane in the presence of a complex of boron TRIFLUORIDE-diethyl ether, triperoxonane acid or the like

Scheme 14

Formula 22

where X has the above meaning; R17has the same meaning as indicated above for the Rb; and Ar2has the above value.

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 15, as shown below.

Scheme 15

Formula 23

where R18has the same meaning as indicated above for the Rb; and Ar has the above meaning.

Namely, the compound (XXXX-I) can be obtained by exposure to a suitable alkyllithium connection (for example, n-utility or the like) to the compound (XXXVIII) to interact with the compound (V) and catalytic hydrogenation of the obtained compound (XXXIX-I) using a palladium catalyst or the like in the same way the connection (XXXX-II) can be directly obtained by catalytic hydrogenation of the compound (XXXIX-II) using a palladium catalyst, or it can be obtained by acetylation of the hydroxy-group with the subsequent removal of acetochlor and ensiling groups by the reaction of catalytic hydrogenation using palladium catalyst or the like (if necessary, add the acid, such as hydrochloric acid). In this case, the compound (XXXVIII) can be synthesized, for example, by the method described in International Publication No. WO01/27128.

The compound (XXXX) can also be obtained, for example, in accordance with the method presented in figure 16, as shown below.

Scheme 16

Formula 24

where X23and X24represent the atoms of halogen; R18has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely provide exposure to a suitable alkyllithium connection (for example, n-utility or the like) to the compound (XXXXI) and the interaction of this compound with the compound (V) to obtain compound (XXXXII), and the resulting hydroxy-group is converted into thiocarbanilide by methyldiethanolamine or imidazoledicarbonitrile, then perform deoxygenation the influence of radical reagent (e.g., reagent, representing a tin hydride, such as anti-hydride, silane reagent such as diphenylsilane, combination diphosphonate acid or diethylphosphate with tertiary amine) compound (XXXXII) in the presence of a suitable radical initiator (for example, 2,2'-azobisisobutyronitrile, benzoyle the oxide or the like) for the synthesis of compound (XXXXIII). Then the compound (XXXXIII) is converted into benzylguanine (XXXXIV) in suitable conditions of halogenation (e.g., using N-bromosuccinimide, bromine, hydrogen bromide or the like), and benzylamine (XXXXIV) is subjected to interaction with arylhalides (including heteroaromatic) in the presence of a suitable catalyst [for example, tetranitroaniline (0), 1,2-bis(diphenylphosphinoethyl)-dichloropalladium (II) or the like] and then perform dibenzylamine obtaining compound (XXXX).

The intermediate compound (XXXXIV) can be obtained by the method presented in figure 17, as shown below.

Scheme 17

Formula 25

where R18has the same meaning as indicated above for Rb; R represents a protective group; X represents a halogen atom and Ar2has the above value.

Namely, after protection of the hydroxy-group of the compound (XXXXVI] using a suitable protective group (e.g. tert-butyldimethylsilyloxy group, tetrahydropyranyloxy group or the like) of the compound obtained is treated with a suitable alkyllithium connection (for example, n-butyllithium or the like) and subjected to interaction with compound (V) to obtain compound (XXXXVII). Then the tertiary hydroxy-group transform, for example, in thiocarbanilide by metallic is boilerhouse or imidazoledicarbonitrile, and then provide the impact of radical reagent (e.g., reagent, representing a tin hydride, such as anti-hydride, silane reagent such as diphenylsilane, combination diphosphonate acid or diethylphosphate with a tertiary amine) to the compound obtained in the presence of a suitable radical initiator (for example, 2,2'-azobisisobutyronitrile, benzoyl peroxide) to convert the compound (XXXXVIII). Then carry out the removal of protection connection (XXXXIX) and then by means of suitable conditions of halogenation (for example, when X is a bromine atom, these conditions include the use of N-bromosuccinimide, bromine, tetrabromide carbon or the like in the presence of triphenylphosphine) can be synthesized compound (XXXXIV).

The compound (L) can also be obtained, for example, according to Scheme 18, as shown below.

Scheme 18

Formula 26

where R11has the same meaning as indicated above for the Rb; and Ar2has the above value.

Namely, the compound (L) of the present invention can be obtained by using the compound (LI) or a compound (LII) instead of the compound (IV) in the production method, presented in figure 5. The compound (LI) can be synthesized by the method described in document [J. Org. hem., 63, 5668 (1998)], and the compound (LII) can be synthesized by the method described in document [Tetrahedron, 56, 7109 (2000)].

In addition, the compounds of the present invention can also be obtained, for example, according to Scheme 19, as shown below.

Scheme 19

Formula 27

where R17has the same meaning as indicated above for Rb; X has the above meaning; Tf represents trifloromethyl group and Ar2has the above value.

Namely, the compound (LV) can be obtained by treating compound (LIV), obtained by converting compound (V) in triflate connection, together with compound (LVII), obtained by providing exposure to a suitable alkyllithium compounds (n-utility or the like) to the compound (XXXIII)to be processed is the ester of boric acid (trimethylboron or the like)in the presence of palladium catalyst (tetranitroaniline or the like). The compound (LVI) can be obtained by treating this compound (LV) trichloride boron or the like in the presence of pentamethylbenzene or similar

The method of obtaining the compounds of the present invention is not limited to the above-described methods. Compounds of the present invention can be synthesized, for example, by a suitable combination of stages included in the Scheme 1-19.

The technical result of the present invention

Compounds of the present invention not only have activity of inhibiting SGLT2, but also have suitable properties as a medicinal product, such as metabolic stability, oral absorbiruyaci, duration of drug action and safety. Thus, the present invention is provided a pharmaceutical composition having an action to reduce the level of sugar in the blood, which are used for the prevention or treatment of diabetes, such as insulin-dependent diabetes mellitus (diabetes type I) and insulin-independent diabetes mellitus (type II diabetes), diabetic complications or obesity-induced hyperglycemia.

EXAMPLES

The content of the present invention hereinafter disclosed in more detail using the following examples and experimental examples, but the present invention is not limited to their content.

Each abbreviation in the following examples has the following value.

NMR: the spectrum of nuclear magnetic resonance (TMS internal standard);

MS: mass spectrometric analysis;

HPLC: high performance liquid chromatography.

Data of NMR, MS and HPLC is obtained using the following equipment.

NMR: JOEL JNM-EX-270 (mg), Varian Mercury 300 (300 MHz) or a JOEL JNM-ECP 400 (400 MHz);

MS: LCQ from the company Thermo Finigan or Micromass ZQ from the company Waters;

HPLC: 2690/2996 (Detector) from the company Waters.

The measurement conditions for HPLC following, unless otherwise indicated.

Column: YMC-Pack ODS-A of 6.0×150 mm, 5 ám.

Mobile phase: Elution with a gradient from 0.1% TFA/MeCN (5%) plus of 0.1% TFA/H2O (95%) to 0.1% TFA/MeCN (100%) for 20 minutes and then in the same conditions [of 0.1% TFA/MeCN (100%)] within five minutes.

Flow rate: 1.5 ml/min.

The column temperature: room temperature.

Conditions detection: the entire wavelength range from 230 to 400 nm.

Example 1

[2-(4-Methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of methyl ester of 2-(2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glyukopiranozil)benzoic acid

To a solution in THF (400 μl) methyl salicylate (72 μl, 0,557 mmol) was added triphenylphosphine (146 mg, 0,557 mmol) and 2,3,4,5,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (200 mg, 0,371 mmol), the mixture was added dropwise diethylazodicarboxylate (DEAD, 88 μl, 0,557 mmol) and the resulting mixed solution was stirred at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified preparative thin-layer chromatography (TLC) [eluent=ethyl acetate:n-hexane (1:3)] to obtain specified in the title compound (123 mg, 49%).

1H-MR (CDCl 3) δ: 1,60-1,80 (2H, m), 2,15-of 2.24 (1H, m), 3,48-of 3.64 (4H, m), 3.75 to 3,90 (1H, m), 3,83 (3H, s), 4,43 (3H, s), a 4.53 (1H, d, J=10,7 Hz), 4,51-to 4.98 (6H, m), 6,95-7,02 (1H, m), 7,10-7,50 (22H, m), 7,78 (1H, DD, J=1,65, of 7.75 Hz)

MS (ESI+): 695 [M+Na]+

(2) Synthesis of 2-(2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glyukopiranozil)benzyl alcohol

Sociallyengaged (10.4 mg, 0,274 mmol) was added in small portions to a solution in THF (360 ml) of methyl ester of 2-(2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glyukopiranozil)benzoic acid (123 mg, 0,183 mmol) and the reaction mixture was stirred on an oil bath (55°C) for three hours. The reaction mixture was cooled to room temperature, and then to the mixture was added water and was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified preparative TLC [eluent=ethyl acetate:n-hexane (1:3)] to obtain specified in the title compound (95 mg, 81%).

1H-NMR (CDCl3) δ: 1,60-1,80 (2H, m), 2,16-2,22 (1H, m), 3.46 in-3,74 (5H, m), 4,43 (3H, s), of 4.54 (1H, d, J=10,7 Hz), of 4.66 (2H, users), 4,81-4,96 (5H, m), 6,94-7,31 (24H, m)

MS (ESI+): 667 [M+Na]+

(3) Synthesis of 2-(2, 3, 4,6-Tetra-O-benzyl-5a-carb-β-D-glyukopiranozil)benzaldehyde

To a solution in dichloromethane (1.5 ml) of 2-(2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glyukopiranozil)benzyl alcohol (95 mg, 0.147 mmol) was added to the reagent des the a-Martin (94 mg, 0,221 mmol) and the resulting mixed solution was stirred at room temperature for 45 minutes. Insoluble substances were removed from the reaction mixture by filtration and the filtrate was concentrated under reduced pressure. The obtained residue was purified preparative TLC [eluent=ethyl acetate:n-hexane (1:3)] to obtain specified in the title compound (77 mg, 81%).

1H-NMR (CDCl3) δ: 1,60-1,80 (2H, m), 2,17-of 2.23 (1H, m), 3,48-of 3.78 (5H, m), of 4.44 (3H, s), of 4.54 (1H, d, J=10,7 Hz), 4,73 is equal to 4.97 (5H, m), 7,00-7,32 (22H, m)to 7.50 (1H, DD, J=1,48, 7,83 HZ), 7,83 (1H, DD, J=1,49, 7,58 Hz), 10,4 (1H, )

(4) Synthesis of [2-(2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glyukopiranozil)phenyl]-4-methoxyphenylalanine

To a solution in diethyl ether (120 ml) of 2-(2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glyukopiranozil)benzaldehyde (77 mg, 0,119 mmol) was added a solution of 0.5 M 4-methoxybenzylamine in THF (480 μl, 0,238 mmol) and the resulting mixed solution was stirred at room temperature for 13 hours. To the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was dried (anhydrous magnesium sulfate) and the solvent was concentrated under reduced pressure. The obtained residue was purified preparative TLC [eluent=ethyl acetate:n-hexane (1:3)] to obtain specified in the title compound (66 mg, 74%).

1H-NMR (CDCl3) δ: 1,60-1,80 (2H, m), 1,95-of 2.09 (1H, m), 2,66 (1H, d, J=4,78 Hz), 3,38-3,79 (5H, m), 3,65 1,2H, C)3,69 (1,8H, s), 4,33-4,93 (9H, m), 5,96-6,16 (1H, m), 6.73 x-7,42 (28H, m)

MS (ESI+): 773 [M+Na]+

(5) Synthesis of [2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

To [2-(2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranosyl)phenyl]-4-methoxyphenylalanine (66 mg, 0,0879 mmol) was added a methanol solution of hydrochloric acid (2 ml)containing 20% palladium hydroxide on carbon (10 mg)and the reaction mixture was stirred in hydrogen atmosphere for three hours. Upon completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure and the obtained residue was purified preparative TLC [eluent=methanol:dichloromethane (1:10)] to obtain specified in the title compound (20 mg, 61%).

1H-NMR (CD3OD) δ: 0,89-1,03 (1H, m), 1,40-1,60 (1H, m), 2,02-2,10 (1H, m), 3,18-to 3.34 (2H, m), 3,45-3,51 (2H, m), 3,67-3,71 (1H, m), of 3.73 (3H, s), 3,82-3,99 (2H, m), 4,13-4,22 (1H, m), is 6.78 (2H, d, J=to 8.57 Hz), 6,80-6,86 (1H, m), 6,99-7,16 (5H, m)

MS (ESI+): 397 [M+Na]+

Retention time HPLC: 10.6 minutes

Example 2

[1S,2R,3R,4R,6S]-4-Hydroxymethyl-6-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3-triol

(1) Synthesis of [2R,3S,4R,5R]-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[3-(4-methoxybenzyl)phenyl]cyclohexanol

To a solution of 3-(4-methoxybenzyl)-1-bromine benzol (155 mg, 0,559 mmol) in THF (0,80 ml) was added dropwise a solution of 2.44 M n-utility in hexane (0,23 ml, 0,559 mmol) at -78°C and the obtained mixed solution was stirred for 25 m the chickpeas. Then to the mixture was added dropwise a solution of 2,3,4-trebaseleghe-5-(benzoyloxymethyl)cyclohexanone (200 mg, 0,373 mmol) in THF (0,70 ml) and the reaction mixture was stirred for 75 minutes. To the reaction mixture were added saturated aqueous solution of ammonium chloride, the mixture was extracted with ethyl acetate, the organic layer was washed saturated aqueous sodium chloride and then dried over anhydrous magnesium sulfate. The solvent was concentrated and the obtained residue was purified by chromatography on silica gel [eluent=ethyl acetate:n-hexane (2:5)] to obtain specified in the title compound (80 mg, 27%) as a mixture of 1R-isomer and 1S-isomer.

1H-NMR (CDCl3) δ: 1,82-of 1.92 (1H, m), 2,39 is 2.44 (1H, m), 2,56-of 2.64 (1H, m), 3,34-3,39 (1H, m), 3,55-of 3.80 (2H, m), 3,66 (3H, s), of 3.78 (2H, s), a 3.87-of 3.94 (2H, m), 4,42-5,04 (8H, m), 6,61-6,84 (4H, m), 7,06-7,40 (23H, m), 7,55-7,66 (1H, m)

(2) Synthesis of [2R,3S,4R,5R]-2,3,4-Tris-benzyloxy-5-benzoyloxymethyl-1-[3-(4-methoxybenzyl)phenyl]cyclohexylamino ether acetic acid

To a solution of [2R,3S,4R,5R]-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[3-(4-methoxybenzyl)phenyl]cyclohexanol (20 mg), triethylamine (0,008 ml) and 4-dimethylaminopyridine (0.7 mg) in dichloromethane (0.10 ml) was added under ice cooling, acetic anhydride (0.003 ml) and the reaction mixture was stirred at room temperature for two hours. Then to the mixture was added acetylchloride (0.003 ml) under ice cooling and re is clonney the mixture was stirred at room temperature for 30 minutes. To the mixture was added saturated aqueous sodium hydrogen carbonate solution, the mixture was extracted with dichloromethane and the organic layer was dried over anhydrous magnesium sulfate. The solvent was concentrated and the obtained residue was purified preparative TLC [eluent=ethyl acetate:n-hexane (2:5)] to obtain specified in the title compound (4.2 mg).

1H-NMR (CDCl3) δ: 1,85 (3H, s), 2,03-2,17 (2H, s), 3,20-to 3.49 (3H, m), 3,60-and 3.72 (2H, m)to 3.67 (3H, s), a 3.87 (2H, s)4,07 (1H, d, J=9.9 Hz), 4,39-4,95 (8H, m), 6,72 (2H, d, J=8.6 Hz), 6,99-7,40 (24H, m), 7,54 (1H, d, J=7,8 Hz), the 7.65 (1H, s)

MS (ESI+): 794 [M+H2On]+

(3) Synthesis of [1S, 2R,3R,4R,6S]-4-hydroxymethyl-6-[3-(4-methoxybenzyl)phenyl]cyclohexane-1,2,3-triol

To a solution in methanol (0.2 ml)-THF (0.2 ml) of [2R,3S,4R,5R]-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[3-(4-methoxybenzyl)phenyl]cyclohexylamino ether acetic acid (4.2 mg) was added 20% palladium hydroxide on carbon (3 mg) and the resulting mixed solution was stirred in hydrogen atmosphere for three hours. The reaction mixture was filtered, the filtrate was concentrated and the obtained residue was purified preparative TLC [eluent=dichloromethane:methanol (9:1)] to obtain specified in the title compound (1.7 mg) as a single diastereoisomer.

1H-NMR (DMSO-d6) δ: 1,24 (1H, DD, J=12,9, and 12.6 Hz), to 1.48 (1H, m), of 1.65 (1H, dt, J=13,8, and 3.3 Hz), 2,43 (1H, dt, J=10,4, 4,2 Hz), 3,05-3,17 (2H, m), 3,26 is 3.40 (2H, m), of 3.60 (1H, m), 3,71 (3H, s), 3,83 (2H, s), is 4.15 (1H, d, J=4,8 Hz), is 4.21 (1H, is, J=5,1 Hz), of 4.45 (1H, usher.), 4,60 (1H, usher.), at 6.84 (2H, m), 6,93-was 7.08 (3H, m), 7,10-7,20 (3H, m)

MS (ESI+): 376 [M+H2On]+

Example 3

[2-(4-Cryptomaterial)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(trifloromethyl)-methanol

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 8,7 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (3.3 grams, 12,64 mmol) in THF (126 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for 15 minutes. To this solution was added dropwise at -78°C solution of 4-triphtalocyaninine (2.0 g, 10,52 mmol) in THF (42 ml). The reaction mixture was stirred at the same temperature for 40 minutes and at 0°C for 45 minutes, then to the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compound (3.03 g, 77%) as a colourless oil.

1H-NMR (CDCl3) δ: 2,98 (1H, d, J=5.8 Hz), free 5.01 (2H, s), of 6.02 (1H, d, J=5.6 Hz), 6,84-7,00 (2H, m), 7.03 is-7,37 (11H, m)

(2) Synthesis of 2-(4-cryptomaterial)phenol

Catalysis the top 20% palladium hydroxide (150 mg) was added to a solution of (2-benzyloxyphenyl)-(4-trifloromethyl)methanol (1.5 g, to 4.01 mmol) in methanol (27 ml), and then to the mixture was added 36% HCl solution (0.33 ml). The obtained mixed solution was stirred in an atmosphere of hydrogen for 16 hours and then was cooled to 0°C, the mixture was added potassium carbonate (0.54 g) and the mixture was stirred for 30 minutes, and then the catalyst was removed by filtration. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compounds as white solids (of 1.05 g, 97%).

1H-NMR (CDCl3) δ: 3,98 (2H, s), a 4.83 (1H, s), 6,77 (1H, d, J=7,7 Hz), 6.89 in (1H, t, J=7,3 Hz), 6,99-7,13 (4H, m), 7.23 percent (2H, d, J=8.1 Hz)

(3) Synthesis of [2-(4-cryptomaterial)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (400 mg, of 0.74 mmol) and tributylphosphine (of 0.28 ml, 1.11 mmol) was added under ice cooling to a solution of 2-(4-tri-formicoxenini)phenol (298 mg, 1.11 mmol) in toluene (2.5 ml)was then added at the same temperature tetramethyldisiloxane (TMAD, 191 mg, 1.11 mmol). The reaction mixture was stirred overnight while gradually increasing the temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=those who acetate:n-hexane (1:10)], and then preparative TLC [eluent=ethyl acetate:n-hexane (1:5)]. The crude product was dissolved in a mixed solution of tetrahydrofuran (1.4 ml)-methanol (2.8 ml), the mixture was added the catalyst of 20% palladium hydroxide (40 mg) and the mixture was stirred in hydrogen atmosphere for about 1.75 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified preparative TLC [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (67 mg, 21%).

1H-NMR (CD3OD) δ: 0,85-0,99 (1H, m), 1,44-to 1.61 (1H, m), 2,00-2,11 (1H, m), 3,12-to 3.33 (2H, m), 3,38-of 3.48 (2H, m), 3,64-to 3.73 (1H, m), 3,93 (1H, d, J=14,8 Hz), 4,07 (1H, d, J=14,8 Hz), 4,12-to 4.23 (1H, m)6,86 (1H, t, J=7,3 Hz), of 6.96-7,17 (5H, m), 7,29 (2H, d, J=8.6 Hz)

MS (ESI+): 428 [M]+

Retention time HPLC: 12.7 minutes

Example 4

[2-(4-Cyclopentylmethyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(4-bromophenyl)methanol

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 11,57 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (4.4 g, 16,72 mmol) in THF (168 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for 15 minutes. To this solution was added dropwise at -78°C solution of 4-bromobenzaldehyde (2,47 g, 13,34 mmol) in THF (50 ml). The reaction mixture was stirred at the same temperature for 30 minutes and n and 0°C for 30 minutes, then to the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the connection header (4,08 g, 83%) as a colourless oil.

1H-NMR (CDCl3) δ: 2,96 (1H, d, J=6,1 Hz), free 5.01 (2H, s), 5,97 (1H, d, J=5,9 Hz), 6,86-6,99 (2H, m), 7,09-7,39 (11H, m)

(2) Synthesis of 1-benzyloxy-2-(4-bromobenzyl)benzene

In a stream of nitrogen triethylsilane (1,84 ml, 11,55 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (of 1.33 ml, 10.5 mmol) was added to a solution of (2-benzyloxyphenyl)-(4-bromophenyl)methanol (3.88 g, 10.5 mmol) in acetonitrile (19,5 ml) at -40°C and the mixture was stirred at the same temperature for 0.5 hours. To the reaction mixture were added saturated aqueous solution of potassium carbonate and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compound (2.86 g, 77%.

1H-NMR (CDCl3) δ: 3,95 (2H, s), of 5.03 (2H, s), for 6.81-6,92 (2H, m), of 6.96 and 7.36 (11H, m)

(3) Synthesis of 1-[4-(2-benzyloxybenzyl)phenyl]Cyclopentanone

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 294 ml) was added dropwise to a solution of 1-benzyloxy-2-(4-bromobenzyl)benzene (1.5 g, of 4.25 mmol) in THF (16.5 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To this mixture was added dropwise at -78°C a solution of Cyclopentanone (357 mg, 4,2 5 mmol) in THF (4 ml). The reaction mixture was stirred at the same temperature for 50 minutes and at 0°C for one hour, then to the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the connection header (1,14 g, 75%) as a colourless oil.

1H-NMR (CDCl3) δ: 1,47-2,02 (8H, m)4,00 (2H, s), of 5.03 (2H, s), 6,79-6,89 (2H, m), 7,02 and 7.36 (11H, m)

(4) Synthesis of 2-(4-cyclopentylmethyl)phenol

To a solution of 1-[4-(2-benzyloxybenzyl)phenyl]Cyclopentanone (1,14 g, 3,19 mmol) in methanol (21 ml) was added catalyst a 20% palladium hydroxide (114 mg), and then to the mixture was added 36 HCl (0,255 ml). The mixture was stirred in hydrogen atmosphere overnight and then cooled to 0°C, the mixture was added potassium carbonate (425 mg) and the mixture was stirred for 20 minutes, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:20)] to obtain specified in the connection header (744 mg, 92%) as a white solid.

1H-NMR (CDCl3) δ: 1,44-of 1.84 (6H, m), 1.93 and-of 2.09 (2H, m), 2,84-of 3.00 (1H, m), of 3.95 (2H, s), was 4.76 (1H, s)6,76 (1H, d, J=8.1 Hz), 6.87 in (1H, t, J=7,3 Hz), 7,02-7,20 (6H, m)

(5) Synthesis of [2-(4-cyclopentylmethyl)phenyl]-5a-carb-β-D - glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-cyclopentylmethyl)phenol (351 mg, of 1.39 mmol) in toluene (3.1 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred overnight while gradually increasing the temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=n-hexane:dichloromethane:acetone (12:3:1)] to obtain the crude product (555 mg). Received n is the purified product was dissolved in a mixed solution of tetrahydrofuran (0.9 ml)-methanol (1.8 ml), to the mixture was added the catalyst of 20% palladium hydroxide (12.6 mg) and the mixture was stirred in hydrogen atmosphere for seven hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified preparative TLC [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (40 mg, 58%).

1H-NMR (CD3OD) δ:,79-0,96 (1H, m), 1,44 is 1.86 (7H, m), 1.93 and-2,07 (3H, m), 2,84-2,99 (1H, m), 3,12-and 3.31 (2H, m), 3,37-of 3.48 (2H, m), 3,62-3,71 (1H, m), 3,86 (1H, d, J=14,8 Hz), 3,98 (1H, d, J=14,8 Hz), 4,08-4,20 (1H, m), 6,83 (1H, t, J=7,3 Hz), 6,93-7,14 (7H, m)

MS (ESI+): 413 [M+H]+

Retention time HPLC: 14.5 minutes

Example 5

[2-(4-Chlorobenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(4-chlorophenyl)-methanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 10.3 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (6.0 g, of 22.8 mmol) in THF (228 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C solution of 4-chlorobenzaldehyde (2.67 g, 19.0 mmol) in THF (76 ml). The reaction mixture was stirred at the same temperature for two hours and then at 0°C for one hour. To the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride and dried (be the aqueous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (4,76 g, 77%).

1H-NMR (CDCl3) δ: 2,94 (1H, s), free 5.01 (2H, s), of 5.99 (1H, s), 6,92-7,00 (22H, m), 7,17-7,41 (11H, m)

(2) Synthesis of 1-benzyloxy-2-(4-Chlorobenzyl)benzene

In a stream of nitrogen triethylsilane (2.8 ml, 17.6 mmol) and the complex of boron TRIFLUORIDE-diethyl ether (1,84 ml, 14.6 mmol) was added to a solution of (2-benzyloxyphenyl)-(4-chlorophenyl)methanol (4,76 g, 14.6 mmol) in acetonitrile (150 ml) at -40°C and the reaction mixture was stirred at the same temperature for 2 hours and then at 0°C for one hour. To the mixture was added water and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the connection header (3,85 g, 85%).

1H-NMR (CDCl3) δ: of 3.97 (2H, s), of 5.03 (2H, s), 6.87 in-6,92 (2H, m), 7,08-7,37 (11H, m)

(3) Synthesis of 2-(4-Chlorobenzyl)phenol

In a stream of nitrogen dimethyldisulfide (105,1 μl, 2,43 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (51,3 μl, 0.4 mmol) was added under ice cooling to the races is the thief of 1-benzyloxy-2-(4-Chlorobenzyl)benzene (50.0 mg, 0.16 mmol) in methylene chloride (2.0 ml) and the reaction mixture was stirred for 19 hours while gradually raising its temperature to room temperature. Then to the mixture was added water under ice cooling and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (of 33.4 mg, 94%).

1H-NMR (CDCl3) δ: 3,95 (2H, s), 4,60 (1H, s), 6.75 in-is 6.78 (1H, m), 6,86-6,92 (1H, m), 7,07-7,27 (6H, m)

(4) Synthesis of [2-(4-Chlorobenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added under ice cooling to a solution of 2-(4-Chlorobenzyl)phenol (304 mg, 1.55 mmol) in toluene (2 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg, 1,29 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl shall zitat:n-hexane (1:10)]. The crude product was dissolved in methylene chloride (8 ml) and the resulting mixture was added under ice cooling dimethyldisulfide (2,17 ml of 50.2 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (1.08 ml, 8,51 mmol). The reaction mixture was stirred for 25 hours while gradually raising its temperature to room temperature, and then to the mixture was added water under ice cooling and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the connection header (122,6 mg, 35%).

1H-NMR (CD3OD) δ: 0,95 (1H, DD, J=13,2, l1,1 Hz)of 1.53 (1H, m), 2,00-2,09 (1H, m), 3,20 (1H, d, J=8.7 Hz)at 3.25 (1H, d, J=5,1 Hz), 3,43-3,51 (2H, m), 3,68-3,71 (1H, DD, J=3,9, 3,9 Hz), 3,91 (1H, d, J=14,7 Hz), 3,99 (1H, d, J=15 Hz), 4,15-to 4.23 (1H, m), 6,85 (1H, t, J=7.5 Hz), 7,03 (1H, d, J=9.0 Hz), 7,08-of 7.23 (6H, m)

MS (ESI+): 379 [M+H]+

Retention time HPLC: 11.7 minutes

Example 6

(2-Benzoylphenyl)-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-benzylphenol

To a solution of 2-(4-Chlorobenzyl)phenol (exports, as against 618.5 mg, and 2.83 mmol) in methanol (20 ml) was added catalyst a 20% palladium hydroxide (240 mg). The mixture was stirred in hydrogen atmosphere for three days, the ATEM catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the connection header (348,4 mg, 67%).

1H-NMR (CDCl3) δ: 3,99 (2H, s)and 4.65 (1H, s), 6,79 (1H, d, J=8.1 Hz), 6.89 in (1H, t, J=7.5 Hz), 7,09-7,31 (6H, m)

(2) Synthesis of (2-benzoylphenyl)-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-benzylphenol (256,5 mg of 1.39 mmol) in toluene (2 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 21 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (1:1) (14 ml) and the resulting mixture was added the catalyst of 20% palladium hydroxide (118,8 mg) and the mixture was stirred in hydrogen atmosphere for 15 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography n the silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (84 mg, 26%).

1H-NMR (CD3OD) δ: 0,95 (1H, DD, J=12,0, 11.7 Hz), 1,49-to 1.59 (1H, m), 2,03-of 2.09 (1H, m), 3,20 (1H, d, J=9.0 Hz)at 3.25 (1H, d, J=5.7 Hz), to 3.34 (4H, s), 3,44-3,50 (2H, m), 3,68 (1H, DD, J=3,9, 4,2 Hz), of 3.94 (1H, d, J=15 Hz), 4,0 (1H, d, J=15 Hz), 4,13-4,22 (1H, m), at 6.84 (1H, t, J=6.3 Hz), 7,03 (1H, d, J=6.3 Hz), 7,06-7,24 (7H, m)

MS (ESI+): 345 [M+H]+

Retention time HPLC: 10.6 minutes

Example 7

[2-(4-Isopropylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(4-isopropylphenyl)methanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 5,14 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (3.0 g, to 11.4 mmol) in THF (114 ml) at -78°C and the reaction mixture was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C solution of 4-isopropylbenzaldehyde (1,41 g, 9,49 mmol) in THF (38 ml). The reaction mixture was stirred at the same temperature for one hour and then at 0°C for one hour. To the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (2,63 g, 84%).

1H-NMR (CDCl3) δ: 1.26 in (6H, d, J=7.8 Hz), 284-2,94 (1H, m), 5,02 (2H, s), of 6.02 (1H, s), 6.90 to-7,00 (2H, m), 7,15-7,34 (11H, m)

(2) Synthesis of 2-(4-isopropylbenzyl)phenol

To a solution of (2-benzyloxyphenyl)-(4-isopropylphenyl)methanol (2,63 g, a 7.92 mmol) in methanol (50 ml) was added catalyst a 20% palladium hydroxide (263 mg), and then to the mixture was added 2 n HCl (0.4 ml) and the resulting mixed solution was stirred in an atmosphere of hydrogen for 15 hours and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (1.31 g, 73%).

1H-NMR (CDCl3) δ: 1,24 (6H, d, J=7.8 Hz), 2,82 of 2.92 (1H, m), of 3.96 (2H, s), of 4.67 (1H, s), 6,79 (1H, d, J=9.0 Hz), to 6.88 (1H, t, J=8,4 Hz), 7,10-to 7.15 (6H, m)

(3) Synthesis of [2-(4-isopropylbenzyl)phenyl-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-isopropylbenzyl)phenol (315,1 mg of 1.39 mmol) in toluene (2 ml] under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained estato who was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (1:1) (14 ml), the mixture was added the catalyst of 20% palladium hydroxide (127,8 mg) and the mixture was stirred in hydrogen atmosphere for 15 hours and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the connection header (to 97.1 mg, 27%).

1H-NMR (CD3OD) δ: 0,94 (1H, DD, J=12,9, 12.0 Hz), to 1.22 (6H, d, J=6.9 Hz), 1,48 is 1.58 (1H, m), 2,02-of 2.09 (1H, dt, J=3,9, 4,2 Hz), 2,78-2,87 (1H, m), 3,12-3,24 (2H, m), 3.43 points-to 3.49 (2H, m), 3,68 (1H, DD, J=6,6, 4,2 Hz)to 3.89 (1H, d, J=14.4 Hz), 4,01 (1H, d, J=14,7 Hz), 4,13-is 4.21 (1H, m), at 6.84 (1H, t, J=6.3 Hz), 7,02 (1H, d, J=6.3 Hz), 7,06-to 7.15 (6H, m)

MS (ESI+): 387 [M+H]+

Retention time HPLC: 13.1 minutes

Example 8

[2-(4-Cyclopropylmethyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(4-cyclopropylmethyl)methanol

In a stream of nitrogen a solution of n-utility in hexane (2,6 M, 3.5 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2.2 g, 8.3 mmol) in THF (83 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C solution of 4-cyclopropylbenzene (1.1 g, 6,9 mmol) in THF (280 ml). The reaction mixture was stirred at the same temperature for one hour. To the scientists of the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (1.7 g, 75%).

1H-NMR (CDCl3) δ: of 0.65 to 0.69 (2H, m), of 0.92 to 0.97 (2H, m), 1,86-1,90 (1H, m), is 2.88 (1H, d, J=6 Hz), to 5.03 (2H, s), 6,03 (1H, d, J=6 Hz), 7,17-7,26 (5H, m), 7,32-to 7.35 (4H, m)

MS (ESI+): 315 [M+Na]+

(2) Synthesis of 1-benzyloxyphenyl-2-(4-cyclopropylmethyl)benzene

In a stream of nitrogen triethylsilane (0,73 ml, 4.6 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0.5 ml, 4.0 mmol) was added to a solution of (2-benzyloxyphenyl)-(4-cyclopropylmethyl)methanol (1.3 g, 4.0 mmol) in acetonitrile (7 ml) at -40°C and the obtained mixed solution was stirred at the same temperature for 1.5 hours and then at 0°C for 30 minutes. To the mixture was added water and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:7)] to obtain specified in the title compound (1.2 g, 95%).

1H-NMR (CDCl3) δ: 0,63-of 0.67 (2H, m), 0,89-0,9 (2H, m), 1,84-to 1.87 (1H, m), 3,98 (2H, s), is 5.06 (2H, s), 6.87 in-6,97 (4H, m), 7,08-7,26 (4H, m), 7,31-7,37 (5H, m)

MS (ESI+): 332 [M+H2O]+

(3) Synthesis of 2-(4-cyclopropylmethyl)phenol

In a stream of nitrogen dimethyldisulfide (2.2 ml, of 51.7 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (1.1 ml, 8,8 mmol) was added to a solution of 1-benzyloxy-2-(4-cyclo-propylbenzyl)benzene (1.1 g, 3.5 mmol) in methylene chloride (24 ml) under ice cooling and the reaction mixture was stirred for 23 hours while gradually raising its temperature to room temperature. To the mixture was added water under ice cooling and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the connection header (620,7 mg, 79%).

1H-NMR (CDCl3) δ: 0,65-of 0.67 (2H, m), 0,90-0,94 (2H, m), 1.85 to to 1.86 (1H, m), of 3.95 (2H, s), the 4.90 (1H, s), 6,79 (1H, d, J=8.1 Hz), to 6.88 (1H, t, J=7,7 Hz), 7,11 (2H, d, J=8.1 Hz), 7,20 (4H, d, J=7,7 Hz)

MS (ESI+): 247 [M+Na]+

(4) Synthesis of [2-(4-cyclopropylmethyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (557 mg, of 1.03 mmol) and tributylphosphine (0,37 ml, 1.55 mmol) was added to a solution of 2-(4-cyclopropylmethyl)the dryer is La (348 mg, 1.55 mmol) in toluene (3.5 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 267 mg, 1.55 mmol). The reaction mixture was stirred for 15 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in methylene chloride (3.5 ml) and the resulting mixture was added dimethyl sulfide (1.3 ml, 30.3 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0,65 ml, 5.1 mmol). The reaction mixture was stirred for 14 hours while gradually raising its temperature to room temperature, and then to the mixture was added water under ice cooling and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (9:1)] to obtain specified in the connection header (and 97.8 mg, 25%).

1H-NMR (CD3OD) δ: 0,57-0,61 (2H, m), 0,81-of 0.95 (3H, m), 1,50 (1H, s), 1,79-of 1.85 (1H, m), 1,99-2,03 (1H, m), 3,15-to 3.33 (2H, m), 3,42-of 3.48 (2H, m), 3,66-and 3.72 (1H, m), 3,81-to 3.99 (2H, square, J=14 Hz), to 4.41-is 4.85 (1H, m), 6,80-to 7.15 (8H, m)

MS (ESI+): 407 [M+Na]+

Retention time HPLC: 12.3 minutes

Example 9

[2-(4-n-Propylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [2-(4-n-propylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside

1-Benzyloxy-2-(4-cyclopropylmethyl)benzene (640.8 mg, 2.0 mmol)synthesized in Example 8, was dissolved in 2,2-dimethylpropanoate (12 ml), the mixture was added the catalyst of 20% palladium hydroxide (64 mg) and the mixture was stirred for two hours in hydrogen atmosphere, the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)]. To a solution of the crude product (348 mg) in toluene (3.5 ml) was added under ice cooling 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (557 mg, of 1.03 mmol) and tributylphosphine (of 0.39 ml, 1.55 mmol), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAC 267 mg, 1.55 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)]. The crude product RA is tarali 2.2-DIMETHYLPROPANE (15 ml), to the mixture was added the catalyst of 20% palladium hydroxide (159 mg), the mixture was stirred in hydrogen atmosphere for 17 hours and the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (9:1)] to obtain specified in the connection header (164,4 mg).

1H-NMR (CD3OD) δ: from 0.88 to 0.94 (4H, m), 1,48-and 1.63 (3H, m), 2.05 is-is 2.09 (1H, m), 2,52 (2H, t, J=7,7 Hz), 3,13-3,30 (2H, m), of 3.46 (2H, m), 3,70 (1H, m), a 3.87 (1H, d, J=15 Hz), 3,98 (1H, d, J=15 Hz), 4,60-4,88 (1H, m), 6,84 (1H, t, J=7,3 Hz), 7,00-7,16 (7H, m)

MS (ESI+): 387 [M+H]+

Retention time HPLC: 13.3 minutes

Example 10

[2-(4-Trifloromethyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(4-triptoreline)methanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 4.0 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2.6 g, 9.9 mmol) in THF (100 ml) at -78°C and the reaction mixture was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C 4-triftormetilfosfinov (1.6 g, 9.0 mmol). The reaction mixture was stirred at the same temperature for two hours, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride and dried (besod the initial magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (2.6 g, 82%).

1H-NMR (CDCl3) δ: 3,01 (1H, d, J=6.3 Hz), 5,02 (2H, DD, J=11,4, 4,8 Hz), equal to 6.05 (1H, d, J=6.3 Hz), 6,94-7,02 (2H, m), of 6.96-7,16 (2H, m), 7.24 to 7,33 (5H, m), 7,44 (2H, d, J=7,1 Hz), 7,53 (2H, d, J=8.7 Hz)

MS (ESI+): 359 [M+H]+

(2) Synthesis of 2-(4-trifloromethyl)phenol

To a solution of (2-benzyloxyphenyl)-(4-triptoreline)-methanol (2,46 g, 6,85 mmol) in methanol (68,5 ml) was added catalyst a 20% palladium hydroxide (246 mg), and then to the mixture was added 36% HCl solution (0,59 ml) and the resulting mixed solution was stirred in an atmosphere of hydrogen for 3.5 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:8)] to obtain specified in the connection header (1,49 g, 86%).

1H-NMR (CDCl3) δ: a 4.03 (2H, s), 4.72 in (1H, s), 6,77 (1H, d, J=6.0 Hz), 6.89 in (1H, t, J=4,8 Hz), 7,08-to 7.15 (2H, m), 7,33 (2H, d, J=6.0 Hz), 7,52 (2H, d, J=6.0 Hz)

MS (ESI+): 275 [M+Na]+

(3) Synthesis of [2-(4-trifloromethyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-Tr is formatives)phenol (351 mg, of 1.39 mmol) in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (1:1) (5 ml), the mixture was added the catalyst of 20% palladium hydroxide (20 mg) and the mixture was stirred in an atmosphere of hydrogen for 2 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (74 mg, 19%).

1H-NMR (CD3OD) δ: 0,89 (1H, DD, J=11,7, 12.9 Hz), 1,48-to 1.61 (1H, m), is 2.05 (1H, dt, J=13,2, 4,2 Hz), 3,15-to 3.34 (2H, m), 3,42-to 3.49 (2H, m), of 3.69 (1H, DD, J=3,9, and 10.5 Hz), 3.96 points-to 4.15 (2H, DD, J=14,7, 28,2 Hz), 4,17-4,24 (1H, m), 6.87 in (1H, dt, J=1,2, 7.5 Hz), 7,02-7,20 (3H, m), 7,38 (2H, d, J=8.1 Hz), 7,51 (2H, d, J=8,4 Hz)

MS (ESI+): 435 [M+Na]+

Retention time HPLC: 12.3 minutes

Example 11

[2-(4-Methylsulfonylbenzoyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(4-matilal phenylphenyl)-methanol

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 6,92 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2,89 g, 11.0 mmol) in THF (38 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C solution of 4-methylsulfonylbenzoyl (1,67 g, 11.0 mmol) in THF (12 ml). The reaction mixture was stirred at the same temperature for one hour, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (2.14 g, 58%).

1H-NMR (CDCl3) δ: 2,47 (3H, s), of 2.92 (1H, d, J=6.0 Hz), to 5.03 (2H, s), of 6.02 (1H, d, J=6.0 Hz), 6,92-7,00 (2H, m), 7,21-7,34 (11H, m)

(2) Synthesis of 1-benzyloxy-2-(4-methylsulfonylbenzoyl)benzene

In a stream of nitrogen triethylsilane (1.23 ml, 7,72 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0,88 ml of 5.48 mmol) was added to a solution of (2-benzyloxyphenyl)-(4-methylsulfinylphenyl)methanol (2,13 g, 6.3 mmol) in acetonitrile (15 ml) at -40°C and the obtained mixed solution was stirred at the same temperature for 1.5 hours and then at °C for 30 minutes, then to the mixture was added water and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compound (1.9 g, 95%).

1H-NMR (CDCl3) δ: 2,46 (3H, s), of 3.97 (2H, s), of 5.05 (2H, s), 6,85-to 6.95 (2H, m), 7,10-to 7.35 (11H, m)

(3) Synthesis of 2-(4-methylsulfonylbenzoyl)phenol

In a stream of nitrogen dimethyldisulfide (of 7.25 ml, 138 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (2.1 ml of 8.8 mmol) was added to a solution of 1-benzyloxy-(4-methylsulfonylbenzoyl)-benzene (1.9 g, 5.9 mmol) in methylene chloride (15 ml) under ice cooling and the reaction mixture was stirred for 48 hours while gradually raising its temperature to room temperature. To the mixture was added water under ice cooling and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (1.19 g, 91%).

1H-NMR CDCl 3) δ: 2,46 (3H, s), of 3.95 (2H, s), 4,65-of 4.75 (1H, users), is 6.78 (1H, d, J=7,6 Hz), 6.89 in (1H, t, J=7,6 Hz), 7,09-7,21 (6H, m)

(4) Synthesis of [2-(4-methylsulfonylbenzoyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-methylsulfonylbenzoyl)phenol (320 mg, of 1.39 mmol) in toluene (2 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in methylene chloride (10 ml) and the resulting mixture was added under ice cooling dimethyldisulfide (3.28 ml, 63 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0,94 ml, 5.9 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature, then added water under ice cooling and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate, then the solvent is thenali under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the connection header (me 102 28%).

1H-NMR (CD3OD) δ: to 0.80-0.95 (1H, m), 1,45-to 1.60 (1H, m), 2,00-2,10 (1H, m), 2,42 (3H, s), 3,12-to 3.33 (2H, m), 3,40-3,50 (2H, m), 3,63-3,70 (1H, m), 3,86 (1H, d, J=15 Hz), 4,00 (1H, d, J=15 Hz), 4,15-to 4.23 (1H, m), 6,84 (1H, t, J=7.0 Hz), 7,00-to 7.18 (7H, m)

MS (ESI+): 391 [M+H]+

Retention time HPLC: 11.6 minutes

Example 12

[3-fluoro-2-(4-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxy-6-forfinal)-(4-methoxyphenyl)-methanol

To a solution in THF (50 ml) of 2-benzyloxy-6-forventelige (2.25 g, 9.8 mmol)described in International Publication WO 04/048335, was added dropwise in a stream of nitrogen at room temperature a solution of 4-methoxyphenylacetamide in THF (0.5 M, a 21.5 ml). The reaction mixture was stirred at room temperature for 1.5 hours, then to the mixture was added saturated aqueous solution of ammonium chloride under ice cooling and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (2,82 g, 85%).

<> 1H-NMR (CDCl3) δ: of 3.78 (1H, d, J=12 Hz), 3,80 (3H, s), to 4.98 (1H, d, J=12 Hz), of 5.05 (1H, d, J=12 Hz), of 6.20 (1H, d, J=12 Hz), 6,74-6,84 (4H, m), 7,11-7,31 (8H, m)

(2) Synthesis of 3-fluoro-2-(4-methoxy)phenol

To a solution of (2-benzyloxy-6-forfinal)-(4-methoxyphenyl)methanol (2,54, 7,51 mmol) in methanol (20 ml) was added catalyst a 20% palladium hydroxide (381 mg), and then to the mixture was added 2 n HCl solution (2 ml). The obtained mixed solution was stirred in an atmosphere of hydrogen for 24 hours and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (1.48 g, 85%).

1H-NMR (CDCl3) δ: 3,76 (3H, s), of 3.96 (2H, s), the 4.90 (1H, users), to 6.57 (1H, d, J=8.0 Hz), to 6.67 (1H, t, J=8.0 Hz), PC 6.82 (2H, d, J=9.0 Hz), 7,06 (1H, DD, J=8,0, 8.0 Hz), 7,19 (2H, d, J=9.0 Hz)

(3) Synthesis of [3-fluoro-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 3-fluoro-2-(4-methoxybenzyl)phenol (323 mg, of 1.39 mmol) in toluene (2 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room is based temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (1:4) (5 ml) and the resulting mixture was added the catalyst of 20% palladium hydroxide (63 mg). The mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride-methanol (10:1)] to obtain specified in the title compound (86 mg, 24%).

1H-NMR (CD3OD) δ: 0,90-of 1.05 (1H, m), 1,45-to 1.60 (1H, m), 2,00-2,10 (1H, m), 3,17-to 3.35 (2H, m), 3.45 points-to 3.52 (2H, m), 3,65-3,70 (1H, m), and 3.72 (3H, s), 3,93 (2H, s), 4,15-of 4.25 (1H, m), to 6.67 (1H, t, J=8.0 Hz), 6,76 (2H, d, J=9,0 Hz)6,86 (1H, d, J=8.0 Hz), 7,09-to 7.18 (3H, m)

MS (ESI-): 391 [M+H]-

Retention time HPLC: 10.8 minutes

Example 13

[2-(3-Trifloromethyl)phenyl]-5a-carb-β-D-gluco-

paranoid

(1) Synthesis of (2-benzyloxyphenyl)-(3-triptoreline)-methanol

In a stream of nitrogen a solution of n-utility in hexane (2,7 M, 3.4 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2.0 g, 7.6 mmol) in THF (50 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C 4-three is formatively (2.0 g, of 11.4 mmol). The reaction mixture was stirred at the same temperature for three hours, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (2.2 g, 80%).

1H-NMR (CDCl3) δ: 3,03 (1H, d, J=6.3 Hz), equal to 4.97 is 5.07 (2H, m), the 6.06 (1H, d, J=6.3 Hz), 6,95-7,03 (2H, m), 7,16-7,20 (2H, m), 7,26 (1H, DD, J=7,7, 2.0 Hz), 7.29 trend was 7.36 (4H, m), 7,39 (1H, d, J=7,7 Hz), 7,46-of 7.55 (2H, m), to 7.67 (1H, s)

(2) Synthesis of 2-(3-trifloromethyl)phenol

To a solution of (2-benzyloxyphenyl)-(3-Cryptor-were)methanol (3,32 g, 9.3 mmol) in methanol (50 ml) was added catalyst a 20% palladium hydroxide (166 mg), and then to the mixture was added 36% HCl solution (0.2 ml). The obtained mixed solution was stirred in an atmosphere of hydrogen for 72 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)3 with obtaining specified in the connection header (of 2.26 g, 96%).

1H-NMR (CDCl3) δ: Android 4.04 (2H, s), the 4.90 (1H, d, J=2.0 Hz), 6,76 (1H, d, J=8.1 Hz), 6,86-of 6.90 (1H, m), 7,09-7,16 (2H, m), 7,34-7,46 (3H m), to 7.50 (1H, s)

(3) Synthesis of [2-(3-trifloromethyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(3-tri-formatives)phenol (351 mg, of 1.39 mmol) in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (5:2) (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (45 mg) and the mixture was stirred in hydrogen atmosphere for 15 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (56 mg, 14%).

1H-NMR (CD3OD) δ: from 0.88 to 1.02 (1H, m), 1,52 by 1.68 (1H, m), 2,10 (1H, dt, J=13,4, 3,9 Hz), 3,20-to 3.38 (2H, m), 3,45-3,55 (2H, m), 3,74 (1H, DD, J=4,1, to 10.8 Hz), 3,99 (1H, d, J=14,7 Hz), 4,18 (1H, d, J=15,4 Hz), 4,20-4,32 (1H, m), 6,89-,95 (1H, m), was 7.08 (1H, d, J=7,7 Hz), 7,16-7,26 (2H, m), 7,42-7,58 (4H, m)

MS (ESI+): 413 [M+H]+

Retention time HPLC: 12.0 minutes.

Example 14

[2-(4-Methoxybenzyl)-4-were]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 1-benzyloxy-2-bromo-4-methylbenzoyl

To a solution of 2-bromo-4-METHYLPHENOL (1.5 g, 8.0 mmol) in N,N-dimethylformamide (40 ml) was added potassium carbonate (1,32 g, 9.6 mmol), and then to the mixture was added benzylbromide (1,05 ml of 8.8 mmol). The obtained mixed solution was stirred at room temperature for 12 hours, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the connection header (1,72 g, 77%).

1H-NMR (CDCl3) δ: 2,30 (3H, s), 5,12 (2H, s), PC 6.82 (1H, d, J=8,4 Hz), 6,99-7,03 (1H, m), 7,28-7,41 (4H, m), 7,45-of 7.48 (2H, m)

(2) Synthesis of(2-benzyloxy-5-were)-(4-methoxyphenyl)methanol

In a stream of nitrogen a solution of n-utility in hexane (2,7 M 2,75 ml) was added dropwise to a solution of 1-benzyloxy-2-bromo-4-methylbenzene (1,72 g, 6.2 mmol) in THF (50 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for 30 minutes. To e is th solution was added dropwise at -78°C 4-methoxybenzaldehyde (1.27 g, 9.3 mmol). The reaction mixture was stirred at the same temperature for two hours, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the connection header (1,46 g, 70%).

1H-NMR (CDCl3) δ: 2,28 (3H, s), is 2.88 (1H, d, J=9,2 Hz), 3,80 (3H, s)to 5.00 (2H, s), of 5.99 (1H, d, J=5.6 Hz), 6,80-to 6.88 (3H, m), 7,00-7,05 (1H, m), 7,13 (1H, d, J=1,8 Hz), 7,19-7,34 (7H, m)

(3) Synthesis of 2-(4-methoxybenzyl)-4-METHYLPHENOL

To a solution of (2-benzyloxy-5-methoxyphenyl)-(4-methoxyphenyl)-methanol (1,46 g, 4.3 mmol) in methanol (20 ml) was added catalyst a 20% palladium hydroxide (73 mg), and then to the mixture was added 36% HCl solution (0.1 ml). The mixture was stirred in an atmosphere of hydrogen for 72 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (0.8 g, 80%).

1H-NMR (CDCl3) δ: 2,24 (3H, s), of 3.77 (3H, s)to 3.89 (2H, s), 4,55-4,56 (1H, m), 6,65-6,69 (1H, m), 6,80-6,86 (2H, m), 6,88-6,94 (2H, m), 7,11-7,16 (2H, m)

(4) Synthesis of [2-(4-methoxybenzyl)--were]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-methoxybenzyl)-4-METHYLPHENOL (317 mg, of 1.39 mmol) in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (5:2) (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (44 mg) and the mixture was stirred in hydrogen atmosphere for 4 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (88 mg, 24%).

1H-NMR (CD3OD) δ: from 0.88 to 1.02 (1H, m), 1,42 is 1.60 (1H, m), 2,04 (1H, dt, J=13,4, 4.0 Hz), of 2.21 (3H, s), 3,17-of 3.32 (2H, m), 3,43-3,51 (2H, m), 3,70 (1H, DD, J=4,1 and 10.7 Hz), 3,74 (3H, s), 3,82 (1H, d, J=14,7 Hz), 3,92 (1H, d, J=14,7 Hz), 4,06-4,16 (1H, m), 6,77-PC 6.82 (2H, m), 6,86-of 6.96 (3H, m), 7,06-to 7.15 (2H, m)

MS (ESI+): 389 [M+H]+

p> Retention time HPLC: 11.2 minutes

Example 15

[2-(3-Methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(3-methoxyphenyl)methanol

To a solution of 2-benzyloxybenzaldehyde (3.0 g, 14.1 mmol) in THF (50 ml) was added dropwise in a stream of nitrogen to a solution of 4-methoxyphenylacetamide in THF (1.0 in M, of 17.0 ml) under cooling with ice. The mixture was stirred at room temperature for one hour, then to the mixture was added under ice cooling a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)3 with obtaining specified in the connection header (4,92 g, 100%).

1H-NMR (CDCl3) δ: 2,97 (1H, DD, J=1,1 is 6.0 Hz), to 3.73 (3H, s), 4,98-5,10 (2H, m), 6,03 (1H, d, J=6.0 Hz), 6,77-PC 6.82 (1H, m), 6,88-7,01 (4H, m), 7,19-to 7.35 (9H, m)

(2) Synthesis of 2-(3-methoxybenzyl)phenol

To a solution of (2-benzyloxyphenyl)-(3-methoxyphenyl)methanol (1.68 g, of 5.24 mmol) in methanol (50 ml) was added catalyst a 20% palladium hydroxide (168 mg), and then to the mixture was added 36% HCl solution (0.2 ml). The mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst ethyltrimethylammonium drove under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (1.29 g, 100%).

1H-NMR (CDCl3) δ: 3,76 (3H, s), of 3.97 (2H, s), 4,69 (1H, s), 6.73 x-6,92 (5H, m), 7,10-of 7.23 (3H, m)

(3) Synthesis of [2-(3-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added under ice cooling to a solution of 2-(3-methoxybenzyl)phenol (298 mg, of 1.39 mmol) in toluene (3 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (5:2) (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (55 mg) and the mixture was stirred in hydrogen atmosphere for four hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (111 mg, 32%).

1H-NMR (CD3OD) δ: 0,97-1,11 (1H, m), 1,52 by 1.68 (1H, m), 2,12 (1H, dt, J=13,4, 4.0 Hz), 3,22-3,39 (2H, m), 3.49 points of 3.56 (2H,m), 3,72-of 3.78 (1H, m), of 3.78 (3H, s)to 3.92 (1H, d, J=14,8 Hz), of 4.05 (1H, d, J=14,8 Hz), 4,18-4,27 (1H, m), 6,72-6,92 (4H, m), 7,05-7,22 (4H, m)

MS (ESI+): 375 [M+H]+

Retention time HPLC: 10.6 minutes

Example 16

[2-(4-Methoxybenzyl)-4-methoxyphenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-benzyloxy-5-methoxybenzaldehyde

To a solution of 2-hydroxy-5-methoxybenzaldehyde (3.0 g, of 19.7 mmol) in N,N-dimethylformamide (50 ml) was added potassium carbonate (3,27 g, 23.6 mmol), and then to the mixture was added benzylbromide (2,6 ml of 21.7 mmol). The reaction mixture was stirred at room temperature for 24 hours, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (4.8 g, 100%).

1H-NMR (CDCl3) δ: of 3.80 (3H, s), of 5.15 (2H, s), of 6.99 (1H, d, J=9.0 Hz), 7,11 (1H, DD, J=3,4, and 9.1 Hz), 7,32-7,44 (6H, m), 10,50 (1H, s)

(2) Synthesis of (2-benzyloxy-5-methoxyphenyl)-(4-methoxyphenyl)methanol

In a stream of nitrogen to a solution of 2-benzyloxy-5-methoxybenzaldehyde (2.0 g, 8.25 mmol) in THF (50 ml) was added dropwise under ice cooling a solution of 4-methoxyphenylacetamide in THF (0.5 M, and 19.8 ml). Recip is to cancel the mixed solution was stirred at room temperature for one hour, then to the mixture was added under ice cooling a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:1)] to obtain specified in the title compound (2.9 g, 100%).

1H-NMR (CDCl3) δ: 2,85 (1H, d, J=5.4 Hz), 3,76 (3H, s), with 3.79 (3H, s), 4,96 (2H, s), of 5.99 (1H, d, J=5.4 Hz), 6,74 (1H, DD, J=2,8, 9.0 Hz), for 6.81-6.87 in (3H, m)6,94 (1H, d, J=4,1 Hz), 7,19 and 7.36 (7H, m)

(3) Synthesis of 2-(4-methoxybenzyl)-4-methoxyphenol

To a solution of (2-benzyloxy-5-methoxyphenyl)-(4-methoxyphenyl)methanol (2,54 g of 7.25 mmol) in methanol (50 ml) was added catalyst a 20% palladium hydroxide (250 mg), and then to the mixture was added 36% HCl solution (0.25 ml). The mixture was stirred in hydrogen atmosphere for 14 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the connection header (1,62 g, 91%).

1H-NMR (CDCl3) δ: 3,74 (3H, s), of 3.78 (3H, s), 3,90 (2H, s)to 4.41 (1H, users), 6,64-6,86 (5H, m), 7,11-7,16 (2H, m)

(4) Synthesis of [2-(4-methoxybenzyl)-4-methoxyphenyl]-5a-carb-β-D-glucopyranose is Yes

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-methoxybenzyl)-4-methoxyphenol (340 mg, of 1.39 mmol) in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (5:2) (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (40 mg) and the mixture was stirred in hydrogen atmosphere for 6 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (128 mg, 34%).

1H-NMR (CD3OD) δ: 0,94-1,08 (1H, m), 1,45-of 1.62 (1H, m)to 2.06 (1H, dt, J=13,0, 4.0 Hz), 3,20-to 3.34 (2H, m), 3.46 in of 3.56 (2H, m), 3,70-of 3.80 (1H, m), of 3.73 (3H, s), with 3.79 (3H, s), 3,88 (1H, d, J=14,8 Hz), of 3.96 (1H, d, J=14,8 Hz), Android 4.04-to 4.14 (1H, m), to 6.67 (1H, d, J=3.1 Hz), 6,74 (1H, DD, J=3.1 and 8.7 Hz), 6,80-to 6.88 (2H, m), 7,00 (1H, d, J=8.7 Hz), 7,12-to 7.18 (2H, m)

p> MS (ESI+): 405 [M+H]+

Retention time HPLC: 10.2 minutes

Example 17

[2-(4-Methoxybenzyl)-6-were]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-benzyloxy-3-methylbenzaldehyde

To a solution of 2-hydroxy-3-methylbenzaldehyde (3.0 g, 22,07 mmol) in N,N-dimethylformamide (50 ml) was added potassium carbonate (3,65 g of 26.4 mmol), and then to the mixture was added benzylbromide (2,9 ml, and 24.2 mmol). The mixture was stirred at room temperature for 26 hours, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)3 with obtaining specified in the title compound (5.0 g, 100%).

1H-NMR (CDCl3) δ: at 2.36 (3H, s), equal to 4.97 (2H, s), 7,16 (1H, t, J=7.4 Hz), of 7.36-7,49 (6H, m), 7,68 (1H, DD, J=1,4, and 7.8 Hz), 10,26 (1H, d, J=0.5 Hz)

(2) Synthesis of (2-benzyloxy-3-were)-(4-methoxyphenyl)methanol

In a stream of nitrogen to a solution of 2-benzyloxy-3-methylbenzaldehyde (1,87 g, 8.25 mmol) in THF (50 ml) was added dropwise under ice cooling a solution of 4-methoxyphenylacetamide in THF (0.5 M, and 19.8 ml). The mixture was stirred at room temperature for one hour, then to the mixture was added PR is ice cooling a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (2.76 g, 100%).

1H-NMR (CDCl3) δ: at 2.36 (3H, s), 2.63 in (1H, d, J=5.0 Hz), of 3.78 (3H, s), with 4.64-to 4.73 (2H, m), of 6.02 (1H, d, J=5.0 Hz), 6,77-6,86 (2H, m), 7,02-was 7.08 (1H, m), 7,15-7,21 (2H, m), 7,22-7,28 (2H, m), 7,34-7,40 (5H, m)

(3) Synthesis of 2-(4-methoxybenzyl)-6-METHYLPHENOL

To a solution of (2-benzyloxy-3-were)-(4-methoxyphenyl)-methanol (2.76 g, 8.25 mmol) in methanol (30 ml) was added catalyst a 20% palladium hydroxide (276 mg), and then to the mixture was added concentrated hydrochloric acid (0,27 ml). The mixture was stirred in an atmosphere of hydrogen for 18 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (1.75 g, 93%).

1H-NMR (CDCl3) δ: 2,22 (3H, s), of 3.78 (3H, s), 3,93 (2H, s), 4,63 (1H, users), 6,77-6,86 (3H, m), of 6.96-7,05 (2H, m), 7,11-7,17 (2H, m)

(4) Synthesis of [2-(4-methoxybenzyl)-6-were]-5-a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tribute the phosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-methoxybenzyl)-6-METHYLPHENOL (318 mg, of 1.39 mmol) in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 48 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (5:2) (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (72 mg) and the mixture was stirred in hydrogen atmosphere for 4 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (180 mg, 50%).

1H-NMR (CD3OD) δ: 1,16-of 1.35 (2H, m), 1,74-of 1.88 (1H, m), of 2.33 (3H, s), 3,16-3,26 (2H, m), 3,42-to 3.52 (1H, m), 3,54-3,68 (2H, m), 3,74 (3H, s), 3,92-was 4.02 (2H, m), 4,08 (1H, d, J=15.3 Hz), 6,77-6,83 (2H, m), 6,86-6,91 (2H, m,), of 6.96? 7.04 baby mortality (1H, m), 7,05 for 7.12 (2H, m)

MS (ESI+): 411 [M+Na]+

Retention time HPLC: 10.8 minutes

Example 18

[2-(4-Methoxybenzyl)-4-forfinal]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-be is siloxy-5-forfinal)-(4-methoxyphenyl)methanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 2.4 ml) was added dropwise to a solution of 1-benzyloxy-2-bromo-4-fervently (1.5 g, 5.33 mmol) in THF (60 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C solution of 4-methoxybenzaldehyde (0.6 g, was 4.42 mmol) in THF (20 ml). The reaction mixture was stirred at the same temperature for one hour, then to the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (0,98 g, 66%).

1H-NMR (CDCl3) δ: 2,66 (1H, DD, J=0,8, a 4.9 Hz), 3,80 (3H, s), to 4.98 (2H, s), 6,01 (1H, d, J=4.9 Hz), 6,83-of 6.90 (4H, m), 7,14 (1H, DD, J=3,0, 9.0 Hz), 7,20-7,34 (7H, m)

(2) Synthesis of 4-fluoro-2-(4-methoxybenzyl)phenol

To a solution of (2-benzyloxy-5-forfinal)-(4-methoxyphenyl)-methanol (0,98 g, 2,90 mmol) in methanol (18.6 ml) was added catalyst a 20% palladium hydroxide (98 mg), and then to the mixture was added 2 n HCl (1 ml). The mixture was stirred in hydrogen atmosphere for 15 hours, then the catalyst was filtered. The solution is tel drove under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:6)] to obtain specified in the title compound (0.55 g, 82%).

1H-NMR (CDCl3) δ: of 3.78 (3H, s)to 3.89 (2H, s)and 4.65 (1H, users), 6,68-of 6.73 (1H, m), 6,77-6,87 (4H, m), 7,11-7,12 (2H, m)

(3) Synthesis of [2-(4-methoxybenzyl)-4-forfinal]-5a-carb-β-D - glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-methoxybenzyl)-4-terfenol (323 mg, of 1.39 mmol) in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 48 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (5:2) (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (22 mg) and the mixture was stirred in hydrogen atmosphere for four hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (103 mg, 29%).

1H-NMR (CD3OD) δ: 0,99-of 1.13 (1H, m), 1,50-of 1.65 (1H, m), 2,08 (1H, dt, J=1,4, 4,O Hz), 3,22-to 3.35 (2H, m), 3,50 is 3.57 (2H, m in), 3.75 (1H, DD, J=4,0, to 10.7 Hz), with 3.79 (3H, s), a 3.87-was 4.02 (2H, m), 4,11-is 4.21 (1H, m), 6,79 (1H, DD, J=3.1 and 9.4 Hz), 6,83-6,92 (3H, m), 7,06 (1H, DD, J=4,7, and 8.9 Hz), 7,12-7,20 (2H, m)

MS (ESI+): 415 [M+Na]+

Retention time HPLC: 10.9 minutes

Example 19

[2-(3-Terbisil)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(3-forfinal)methanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 5,65 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (3,3 g, 12.5 mmol) in THF (40 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for 30 minutes. To this mixture was added dropwise at -78°C solution of 3-forventelige (1.40 g, 11.3 mmol) in THF (5 ml). The reaction mixture was stirred at the same temperature for one hour, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the connection header (of 2.26 g, 65%).

1H-NMR (CDCl3) δ: 3,00 (1H, d, J=6.3 Hz), to 5.57 (1H, d, J=11.5 Hz), the ceiling of 5.60 (1H, d, J=11.5 Hz), 6,01 (1H, d, J=6.3 Hz), 6,85-to 7.15 (5H, m), 7,17-of 7.4 (7H, m)

MS (ESI+): 308 [M]+

(2) Synthesis of 2-(3-forbesi is)phenol

To a solution of (2-benzyloxyphenyl)-(3-forfinal)methanol (2,54 g, 7,51 mmol) in methanol (30 ml) was added catalyst a 20% palladium hydroxide (300 mg), and then to the mixture was added 2 n HCl (0.3 ml). The obtained mixed solution was stirred in hydrogen atmosphere for five days, and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compound (620 mg, 42%).

1H-NMR (CDCl3) δ: 3,98 (2H, s), 4,70 (1H, s), 6.75 in with 7.3 (8H, m)

MS (ESI+): 201 [M+H]+

(3) Synthesis of [2-(3-terbisil)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (400 mg, 0,743 mmol) and tributylphosphine (0,278 ml, 1.11 mmol) was added to a solution of 2-(3-terbisil)phenol (225 mg, 1.11 mmol) in toluene (2.5 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 192 mg, 1.11 mmol). The reaction mixture was stirred for 14 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude productfactory in a mixed solution of methanol-THF (5:2) (7 ml), to the mixture was added the catalyst of 20% palladium hydroxide (40 mg), the mixture was stirred in an atmosphere of hydrogen for 24 hours and the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (76 mg, 28%).

1H-NMR (CD3OD) δ: 0,99 (1H, DD, J=24,7, 13,2 Hz), 1,45-of 1.62 (1H, m), is 2.09 (1H, dt, J=12,6, 4 Hz), 3,16 to 3.3 (2H, m), 3,4-3,55 (2H, m), 3,71 (1H, DD, J=10,7, 3.8 Hz), 3,93 (1H, d, J=14,9 Hz), of 4.05 (1H, d, J=14,9 Hz), 4,1-4,3 (1H, m), 6,8-to 6.95 (3H, m), 7,0-7,06 (2H, m), 7,08-7,27 (3H, m)

MS (ESI+): 363 [M+H]+, 385 [M+Na]+

Retention time HPLC: 10.9 minutes

Example 20

[2-(3-Methylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [2-(3-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranose (413 mg, 0,743 mmol) and tributylphosphine (0,233 ml, 1.15 mmol) was added under ice cooling to a solution in toluene (2.5 ml) of 2-(3-methylbenzyl)phenol (228 mg, 1.15 mmol), described in Uzbekskii Khimicheskii Zhurnal (1984), 6, 31-4, etc., then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 198 mg, 1.15 mmol). The reaction mixture was stirred for 15 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under pengendalian and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution (2:5) methanol-THF (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (40 mg) and the mixture was stirred in an atmosphere of hydrogen for six hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (109 mg, 40%).

1H-NMR (CD3OD) δ: 0,95 (1H, DD, J=24,4, 12.9 Hz), 1,45-of 1.62 (1H, m)to 2.06 (1H, dt, J=13,1, 4.0 Hz), and 2.27 (3H, s), 3,15-3,30 (2H, m), 3,42-to 3.52 (2H, m), 3,70 (1H, DD, J=10,7, 3,9 Hz), a 3.87 (1H, d, J=14,8 Hz), 3,98 (1H, d, J=14,8 Hz), 4,1-of 4.25 (1H, m), for 6.81-to 6.88 (1H, m), 6,9-7,2 (7H, m)

MS (ESI+): 376 [M+NH4]+, 359 [M+H]+

Retention time HPLC: 11.4 minutes

Example 21

[5-fluoro-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-benzyloxy-1-bromo-4-fermental

Potassium carbonate (2,61 g of 18.8 mmol) was added to a solution of 2-bromo-5-terfenol (3.0 g, 15.7 mmol) in DMF (15.7 ml) and the mixture was stirred in a stream of nitrogen at room temperature for 15 minutes. To this solution was added dropwise at the same temperature benzylbromide (2,69 g, 15.7 mmol) and the resulting mixed solution was stirred at the same temperature throughout the night. To the reaction mixture were added an aqueous solution of potassium bisulfate and the mixture is extra is Aravali with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel (eluent=n-hexane) to obtain specified in the connection header (or 4.31 g, 98%) as a colourless oil.

1H-NMR (CDCl3) δ: 5,14 (2H, s), 6,56-6,72 (2H, m), 7,31-7,52 (6H, m)

(2) Synthesis of (2-benzyloxy-4-forfinal)-(4-methoxyphenyl)methanol

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 3,14 ml) was added dropwise to a solution of 2-benzyloxy-1-bromo-4-fervently (1.4 g, 5.0 mmol) in THF (50 ml) at -78°C and the mixture was stirred at the same temperature for 15 minutes. To this solution was added dropwise at -78°C solution of 4-methoxybenzaldehyde (680 mg, 4,99 mmol) in THF (15 ml) and the mixture was stirred at the same temperature for 1.5 hours, then to the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=n-hexane:dichloro-methane:acetone (12:3:1)] to obtain specified in the connection header (1,41 g, 83%) as bescoto the oil.

1H-NMR (CDCl3) δ: 2,67 (1H, d, J=5.0 Hz), with 3.79 (3H, s), 4,99 (2H, s), 6,00 (1H, d, J=3.8 Hz), 6,62-6,70 (2H, m), for 6.81-6,86 (2H, m), 7,19-7,38 (8H, m)

(3) Synthesis of 2-(4-methoxybenzyl)-5-terfenol

To a solution of (2-benzyloxy-4-forfinal)-(4-methoxyphenyl)-methanol (2,095 g, to 6.19 mmol) in methanol (20 ml) was added catalyst a 20% palladium hydroxide (200 mg), and then to the mixture was added 2 n HCl (0.3 ml). The mixture was stirred in an atmosphere of hydrogen for 16 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the header of the compound (489 mg, 34%).

1H-NMR (CDCl3) δ: of 3.78 (3H, s)to 3.89 (2H, s), 4,88 (1H, s), 6,50-6,40 (2H, m), 6,80-to 6.88 (2H, m),? 7.04 baby mortality (1H, DD, J=6,6, 8,2 Hz), 7,08-to 7.15 (2H, m)

MS (ESI-): 231 [M-H]-

(4) Synthesis of [5-fluoro-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranose (500 mg, 0,928 mmol) and tributylphosphine (0,346 ml of 1.39 mmol) was added to a solution of 2-(4-methoxybenzyl)-5-terfenol (323 mg, of 1.39 mmol) in toluene (2.5 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 240 mg of 1.39 mmol). The reaction mixture was stirred for 17 hours while gradually raising its temperature to room temperature. actionnow the mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution (2:5) methanol-THF (7 ml), the mixture was added the catalyst of 20% palladium hydroxide (40 mg) and the mixture was stirred in hydrogen atmosphere for 22 hours, then the catalyst was filtered. The solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (59 mg, 16%).

1H-NMR (CD3OD) δ: 1.00 m (1H, DD, J=24,4, 12.9 Hz), 1,5-of 1.65 (1H, m), 2,04 (1H, dt, J=13,4, 4,1 Hz), 3,17-to 3.35 (2H, m), 3,43-3,55 (2H, m), 3,65 of 3.75 (1H, m), of 3.73 (3H, s), 3,81 (1H, d, J=15.1 Hz), 3,90 (1H, d, J=15.1 Hz), 4,1-4,22 (1H, m), 6,56 (1H, dt, J=8,5, 2.7 Hz), 6.75 in-to 6.88 (3H, m), 7,0-7,13 (3H, m)

MS (ESI+): 415 [M+Na]+

Retention time HPLC: 11.0 minutes

Example 22

[2-(4-Methylsulfonylbenzoyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(4-methylsulfinylphenyl)-methanol

In a stream of nitrogen a solution of 4-methylsulfonylamino in THF (0.5 M, 35 ml) was added dropwise to a solution of 2-benzyloxybenzaldehyde (2,60 g, 12.2 mmol) in THF (24 ml) at 0°C and the mixture was stirred at room temperature for two hours, then to the mixture was added under ice cooling a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of CHL is reed sodium and dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel[eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the connection header (3,91 g, 95%).

1H-NMR (CDCl3) δ: 2,47 (3H, s), 2.91 in (1H, d, J=5.8 Hz), to 5.03 (2H, s), 6,01 (1H, d, J=6.0 Hz), 6.90 to-7,00 (2H, m), 7,15-to 7.35 (11H, m)

(2) Synthesis of (2-benzyloxyphenyl)-(4-methanesulfonyl)methanol

In a stream of nitrogen m-chloroperbenzoic acid (4,40 g of 22.2 mmol) was added at 0°C to a solution of (2-benzyloxyphenyl)-(4-methylsulfinylphenyl)methanol (3.00 g, of 8.92 mmol) in methylene chloride (25 ml) and the reaction mixture was stirred at the same temperature for 30 minutes. The precipitate was removed by filtration and the filtrate was washed 2 N. aqueous sodium hydroxide solution. The wash solution was extracted with methylene chloride and the combined organic layer was washed with water and saturated aqueous sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure to obtain specified in the connection header (3,18 g, 97%).

1H-NMR (CDCl3) δ: to 3.02 (3H, s), 3,03 (1H, d, J=6.3 Hz), 5,00 (1H, J=11,4 Hz), 5,04 (1H, d, J=11.5 Hz), 6,09 (1H, d, J=6.2 Hz), 6,95-7,03 (2H, m), 7,16-7,22 (2H, m), 7.24 to 7,38 (5H, m), 7,53 (2H, d, J=8.1 Hz), to 7.84 (2H, d, J=8.6 Hz)

(3) Synthesis of 2-(4-methanesulfonylaminoethyl)phenol

In a stream of nitrogen, the catalyst was 20% palladium hydroxide (299 mg) and 36% HCl (150 μl, 1.78 mmol) is obavljale to a solution of (2-benzyloxyphenyl)-(4-methanesulfonyl)methanol (3.00 g, to 8.14 mmol) in a mixture of methanol (30 ml) and ethyl acetate (30 ml) and the mixture was stirred in an atmosphere of hydrogen for six hours. To the reaction mixture were added sodium bicarbonate and the mixture was stirred for 30 minutes to neutralize it, and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:2)] to obtain specified in the connection header (1,81 g, 85%).

1H-NMR (CDCl3) δ: to 3.02 (3H, s)4,06 (2H, s)5,00 (1H, s), 6,77 (1H, d, J=7.9 Hz), 6.89 in (1H, dt, J=7,5, 1.2 Hz), 7,08-7,17 (2H, m), 7,42 (2H, d, J=8.6 Hz), 7,82 (2H, d, J=8,4 Hz)

(4) Synthesis of [2-(4-methanesulfonylaminoethyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, 0,928 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-methylsulfonylbenzoyl)phenol (365 mg, of 1.39 mmol) in a mixture of toluene (2 ml) and THF (1 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 242 mg of 1.41 mmol). The reaction mixture was stirred for 25 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4 to 1:2)]. P the obtained crude product was dissolved in a mixture of methanol (3 ml) and THF (2 ml), to the mixture was added the catalyst of 20% palladium hydroxide (to 27.2 mg) and one drop of 2 n hydrochloric acid and the mixture was stirred in hydrogen atmosphere for 2.5 hours. To the reaction mixture were added an aqueous solution of sodium bicarbonate to neutralize the mixture, and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride: methanol (8:1)] to obtain specified in the title compound (120 mg, 31%).

1H-NMR (CD3OD) δ: 0,91 (1H, DDD, J=13,0, 13,0, 13,0 Hz)of 1.53 (1H, m), 2,03 (1H, DDD, J=13,0, 4,0, 4.0 Hz), of 3.07 (3H, s), 3,19 (1H, DD, J=8,9, and 8.9 Hz), or 3.28 (1H, DD, J=9,0, 9.0 Hz), 3,43 (1H, DD, J=9,0, 9.0 Hz), 3,50 (1H, DD, J=10,7, 6,1 Hz)to 3.67 (1H, DD, J=10,7, 4.0 Hz), was 4.02 (1H, d, J=14,5 Hz), 4,16 (1H, d, J=14,5 Hz), 4,14-4.26 deaths (1H, m), to 6.88 (1H, t, J=6.2 Hz),? 7.04 baby mortality (1H, d, J=8.1 Hz), 7,17 (1H, d, J=7.5 Hz), 7,18 (1H, t, J=7.5 Hz), of 7.48 (1H, d, J=8,4 Hz), 7,80 (1H, d, J=8,4 Hz)

MS (ESI+): 423 [M+H]+, 440 [M+NH4]+, 445 [M+Na]+

Retention time HPLC: 9.0 minutes

Example 23

[2-(4-Terbisil)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-(4-terbisil)phenol

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 4.9 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2,04 g of 7.75 mmol) in THF (60 ml) at -78°C and the mixture was stirred at the same temperature for 20 minutes. To this solution was added dropwise at -78 the C solution of 4-forventelige (801 mg, of 6.45 mmol) in THF (10 ml). The mixture was stirred at the same temperature for 1.5 hours, then to the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure to get crude product (2.35 g) specified in the connection header. To a solution of the crude product in methanol (15 ml) was added catalyst a 20% palladium hydroxide (186 mg), and then to the mixture was added 2 n HCl solution (400 µl). The mixture was stirred in hydrogen atmosphere for three hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (996 mg, 77%).

1H-NMR (CDCl3) δ: 3,95 (2H, s), 4.72 in (1H, s), to 7.77 (1H, DD, J=7,9, 1.1 Hz), to 6.88 (1H, TD, J=7,5, 1.1 Hz), of 6.96 (1H, DD, J=8,7, to 8.7 Hz), 7,06-7,20 (4H, m)

(2) Synthesis of [2-(4-terbisil)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, 0,928 mmol) and tributylphosphine (0,35 ml of 1.40 mmol) was added to a solution of 2-(4-terbisil)phenol (284 mg, of 1.40 mmol) in toluene (3 ml) under ice cooling, and then to the floor the obtained mixture was added at the same temperature tetramethyldisiloxane (TMAD, 241 mg, of 1.40 mmol). The reaction mixture was stirred for 21 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane(1:8 → 1:3)]. The crude product was dissolved in a solvent mixture of methanol (4 ml)-THF (2 ml) and the resulting mixture was added the catalyst of 20% palladium hydroxide (to 18.4 mg) and a drop of 2 n hydrochloric acid and the mixture was stirred in an atmosphere of hydrogen for 1.5 hours. To the reaction mixture were added saturated aqueous solution of sodium bicarbonate to neutralize the mixture and the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent-methylene chloride:methanol (10:1 to 8:1)] to obtain specified in the title compound (153 mg, 46%).

1H-NMR (CD3OD) δ: 0,99 (1H, DDD, J=12,9, and 12.9, 12.9 Hz), of 1.55 (1H, m), of 2.08 (1H, DDD, 3=13,2, a 3.9, 3.9 Hz), up 3.22 (1H, DD, J=9,0, 9.0 Hz), 3,30 (1H, DD, J=9,0, 9,O Hz), 3,48 (1H, DD, J=8,7, to 8.7 Hz), 3,51 (1H, DD, J=10,8, 6,O Hz), 3,70 (1H, DD, J=10,8, 4,2 Hz), 3,90 (1H, d, J=14,7 Hz), was 4.02 (1H, d, J=14,7 Hz), 4,20 (1H, DDD, J=11,4, 9,0, 4,8 Hz), 6,85 (1H, t, J=7.5 Hz), 6,93 (1H, DD, J=8,9, and 8.9 Hz), 7,02 (1H, d, J=8.1 Hz), 7,06-of 7.23 (4H m)

MS (ESI+): 363 [M+H]+

Retention time HPLC: 10.9 minutes

Example 24

[-(3,4-Dimethoxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-(3,4-dimethoxybenzyl)phenol

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 4.4 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (1,74 g of 6.61 mmol) in THF (30 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for one hour. To this solution was added dropwise at -78°C solution of 3,4-dimethoxybenzaldehyde (1,00 g of 6.02 mmol) in THF (8 ml). The reaction mixture was stirred at the same temperature for 1.5 hours, then to the mixture was added saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate)and the solvent is then drove away under reduced pressure to get crude product (2.38 g). The crude product was dissolved in methanol (20 ml) was added catalyst a 20% palladium hydroxide (196 mg), and then to the mixture was added 2 n HCl solution (30 ml). The obtained mixed solution was stirred in hydrogen atmosphere for 23 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the header of the compound (653 mg, 44%).

1H-NMR (CDCl3 ) δ: 3,82 (3H, s), 3,85 (3H, s), of 3.94 (2H, s), to 4.73 (1H, s), 6,74-PC 6.82 (2H, m), 6,78 (1H, s), 6.89 in (1H, TD, J=7,5, 1.1 Hz), 7,08-7,17 (2H, m)

(2) Synthesis of [2-(3,4-dimethoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (504 mg, 0,936 mmol) and tributylphosphine (0,35 ml of 1.40 mmol) was added under ice cooling to a solution of 2-(3,4-dimethoxybenzyl)phenol (342 mg, of 1.40 mmol) in a mixture of toluene (2.5 ml) and THF (1.0 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 242 mg of 1.41 mmol). The reaction mixture was stirred for 22 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:3)]. The crude product was dissolved in a solvent mixture of methanol (2 ml)-THF (2 ml) and the resulting mixture was added the catalyst of 20% palladium hydroxide (to 21.9 mg). The obtained mixed solution was stirred in an atmosphere of hydrogen for five hours, then the catalyst was filtered. The solvent drove in under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride: methanol (10:1)] to obtain specified in the title compound (108 mg, 38%).

1H-NMR (CD3OD) δ: 1,01(1H, DDD, J=13,1, 13,1, and 11.6 Hz), of 1.55 (1H, m), of 2.08 (1H, DDD, J=13.3-inch, and 3.8, and 3.8 Hz), 3,21 (1H, DD, J=9,2, 9,2 Hz), 3,29 (1H, DD, J=8,9, and 8.9 Hz), 3,48 (1H, DD, J=9,2, 9,2 Hz), 3,49 (1H, DD, J=10,7, 6.3 Hz), 3,70 (1H, DD, J=10,7 by 4.1 Hz), 3,76 (3H, s), of 3.78 (3H, s), a 3.87 (1H, d, J=14,8 Hz), of 3.96 (1H, d, J=14,8 Hz), 4,19 (1H, DDD, J=11,5, 9,0, 4.6 Hz), was 6.73 (1H, DD, J=8,3, 2.0 Hz), for 6.81 (1H, s), PC 6.82 (1H, d, J=8,3 Hz), at 6.84 (1H, TD, J=of 7.5, 1.2 Hz), 7,02 (1H, d, J=7.5 Hz), was 7.08 (1H, DD, J=7,5, 1,S Hz), 7,14 (1H, TD, J=7,2, 1.7 Hz)

MS (ESI+): 405 [M+H]+

Retention time HPLC: 9.7 minutes

Example 25

[2-(4-active compounds)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [2-(4-active compounds)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (400 mg, of 0.74 mmol) and tributylphosphine (of 0.28 ml, 1.11 mmol) was added under ice cooling to a solution in toluene (2.5 ml) of 2-(4-active compounds)phenol (236 mg, 1.11 mmol)described in International Publication No. WO04/052902, WO01/074834 etc., then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 191 mg, 1.11 mmol). The reaction mixture was stirred for 25 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a mixed solution of methanol-THF (1:2) (4 ml) and the resulting mixture was added utilizator 20% palladium hydroxide (20 mg). The mixture was stirred in an atmosphere of hydrogen for 1.5 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified using TLC [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (40 mg, 14%).

1H-NMR (CD3OD) δ: 0,86-1,00 (1H, m)to 1.19 (3H, t, J=7,6 Hz), 1,45-of 1.62 (1H, m), 2,00-2,11 (1H, m), 2.57 m (2H, square, J=7,6 Hz), 3,16-3,30 (2H, m), 3.43 points-to 3.49 (2H, m), 3,70 (1H, DD, J=10,6, 4,1 Hz), 3,84-was 4.02 (2H, m), 4,12-4,24 (1H, m), 6,83 (1H, t, J=7.4 Hz), 6,99-7,16 (7H, m)

MS (ESI+): 395 [M+Na]+

Retention time HPLC: 12.3 minutes

Example 26

[2-(4-Hydroxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [2-(4-hydroxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

Under nitrogen atmosphere a solution of tribromide boron in dichloromethane (1,0 M to 0.80 ml, 0.80 mmol) was added to a solution of [2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside (100 mg, 0.27 mmol)obtained in Example 1 in dichloromethane (1.3 ml) at -78°C. the Cooling bath was removed and the reaction mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified using HPLC (eluent=methanol:20 mm aqueous ammonium acetate) to obtain the specified title compound (45 mg, 47%).

1H-NMR (CD3OD) δ: 0,92 was 1.06 (1H, m), 1,47-to 1.67 (1H, m), 2,03-2,11 (1H, m), 3,18-to 3.34 (2H, m), 3.45 points-to 3.52 (2H, m), 3,71 (1H, DD, J=1,7, the 4.1 Hz), 3,79-of 3.95 (2H, m), 4,12-4,22 (1H, m), of 6.65 (2H, d, J=8,4 Hz), 6,83 (1H, t, J=7,3 Hz), 6,99-7,16 (5H, m)

MS (ESI+): 361 [M+H]+

Retention time HPLC: 8.9 minutes

Example 27

[2-(4-Cyanobenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [2-(4-cyanobenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-cyanobenzyl)phenol (291 mg, of 1.39 mmol) in a mixture of toluene (2 ml) and THF (1 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 14 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] and preparative TLC [eluent=ethyl acetate:n-hexane (1:3)] to obtain the crude product (130 mg). The crude product (55 mg) was dissolved in methylene chloride (0,50 ml) and the resulting mixture was added under ice cooling dimethyldisulfide (0,19 ml, 4.4 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0,095 ml, 0.75 mmol). The reaction mixture was stirred at room temperature for five hours, then the mixture EXT is ulali water under ice cooling and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified using TLC [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (17.5 mg, 12%).

1H-NMR (CD3OD) δ: 0,83-to 0.96 (1H, m), 1,44 is 1.60 (1H, m), 1,99-2,07 (1H, m), 3,14-of 3.32 (2H, m), 3,38-3,50 (2H, m)to 3.67 (1H, DD, J=10,7, 4.0 Hz), 3,93 is 4.13 (2H, m), 4,15-4,22 (1H, m), 6,85 (1H, t, J=7,3 Hz), 7,01 (1H, d, J=7.9 Hz), 7,11-to 7.18 (2H, m), 7,37 (2H, d, J=8,2 Hz), 7,55 (2H, d, J=8.1 Hz)

MS (ESI+): 392 [M+Na]+

Retention time HPLC: 10.2 minutes

Example 28

[2-(3-Cryptomaterial)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-(3-cryptomaterial)phenol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 4.3 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2.5 g, 9.5 mmol) in THF (95 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To this mixture was added dropwise at -78°C solution of 3-triphtalocyaninine (1.5 g, 7.9 mmol) in THF (32 ml). The reaction mixture was stirred at the same temperature for two hours and then at 0°C for one hour, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate is), and then the solvent is kept at reduced pressure. The obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)]. The crude product was dissolved in methanol (20 ml) was added catalyst a 20% palladium hydroxide (200 mg), and then to the mixture was added 2 n HCl solution (0,187 ml). The mixture was stirred in hydrogen atmosphere for 13 hours. To the reaction mixture were added potassium carbonate (850 mg) and the mixture was stirred at room temperature for 30 minutes, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (1.40 g, 99%).

1H-NMR (CDCl3) δ: 3,99 (2H, s), 4,71 (1H, users), 6,76 (1H, d, J=7.9 Hz), 6,92-6,86 (1H, m), 7,02-to 7.15 (5H, m), 7,29 (1H, d, J=7,3 Hz)

(2) Synthesis of [2-(3-cryptomaterial)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added under ice cooling to a solution of 2-(3-cryptomaterial)phenol (373 mg, of 1.39 mmol) in toluene (2 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours, when et is m gradually increasing its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a solvent mixture of methanol-THF (1:2) (10 ml), the mixture was added the catalyst of 20% palladium hydroxide (100 mg) and the reaction mixture was stirred in hydrogen atmosphere for 13 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified using TLC [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (104 mg, 26%).

1H-NMR (CD3OD) δ: 0,86-1,00 (1H, m), 1,45-to 1.60 (1H, m), 2,01-of 2.09 (1H, m), 3,15-and 3.31 (2H, m), 3,41-of 3.48 (2H, m), 3,68 (1H, DD, J=10,7, 4,1 Hz), 3,88-4,11 (2H, m), 4,13-of 4.95 (1H, m), PC 6.82-6.87 in (1H, m), 7,00-7,30 (7H, m)

MS (ESI+): 429 [M+H]+

Retention time HPLC: 12.4 minutes

Example 29

[2-(4-Aminomethylbenzoic)phenyl]-5a-carb-β-D-glucopyranoside, salt acetic acid

(1) Synthesis of [2-(4-aminomethylbenzoic)phenyl]-5a-carb-β-D-glucopyranoside, salts of acetic acid.

The crude product (63 mg) [2-(4-cyanobenzyl)phenyl]- 2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside obtained in Example 27 was dissolved in a solvent mixture of methanol-THF (1:2) (1 ml), the mixture was added the catalyst of 20% palladium hydroxide and the resulting mixed solution premesis is whether in hydrogen atmosphere for 23 hours. The catalyst was filtered and the solvent drove under reduced pressure to get crude product [2-(4-aminomethylbenzoic)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside. This crude product was dissolved in methylene chloride (0,55 ml) and the resulting mixture was added under ice cooling dimethyldisulfide (0,22 ml, 5.1 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0,11 ml, 0.86 mmol) and the mixture was stirred at room temperature for 22 hours. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified using HPLC (eluent=methanol:20 mm aqueous ammonium acetate) to obtain the specified title compound (19 mg).

1H-NMR (CD3OD) δ: 0,85-0,99 (1H, m), 1,42 is 1.58 (1H, m), a 1.88 (3H, s), 1.93 and is 2.01 (1H, m), 3,14-to 3.67 (5H, m), a 3.87-4,07 (2H, m)to 4.01 (2H, s), 4,11-4,20 (1H, m), 6,79-6,85 (1H, m), of 6.99 (1H, d, J=4,1H), 7,01-7,16 (2H, m)to 7.25 (2H, d, J=8,4 Hz), 7,29 (2H, d, J=8,5 Hz)

MS (ESI+): 374 [M+H]+

Retention time HPLC: 7.3 minutes

Example 30

[5-Methoxy-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [5-methoxy-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 5-methoxy-2-(4-methoxybenzyl)phenol (340 mg, of 1.39 mmol)described in International Publication No. W004/058682, WO02/064606, WO0/044192 or the like, in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 17 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:3)]. The crude product was dissolved in a solvent mixture of methanol-THF (1:2) (5 ml) and the resulting mixture was added the catalyst of 20% palladium hydroxide (50 mg), the reaction mixture was stirred in hydrogen atmosphere for three hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified using TLC [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (119 mg, 32%).

1H-NMR (CD3OD) δ: 0,84-0,98 (1H, m), 1,44 is 1.60 (1H, m), 1,98 e 2.06 (1H, m), 3,13-3,47 (5H, m), of 3.77 (3H, s), 3,82 (3H, s), 3,71-3,88 (2H, m), 4,06-4,16 (1H, m), 6,41 (1H, DD, J=2,3, 8,2 Hz), to 6.58 (1H, d, J=2.1 Hz), 6.75 in (2H, d, J=8.7 Hz), 6,94 (1H, d, J=8,2 Hz), 7,05 (2H, d, J=8.6 Hz)

MS (ESI+): 405 [M+H]+

Retention time HPLC: 10.7 minutes

Example 31

[2-(4-Methoxycarbonylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of methyl ester 4-[(2-benzyloxyphenyl)hydroxymethyl]benzoic acid

In a stream of nitrogen a solution of n-utility in hexane (2,71 M, 12.1 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (7,84 g, to 29.8 mmol) in THF (300 ml) at -78°C and the reaction mixture was stirred at the same temperature for 30 minutes. To this mixture was added dropwise at -78°C solution of 4-methyl ether-benzaldehyde (4,78 g of 29.1 mmol) in THF (100 ml). The reaction mixture was stirred at the same temperature for one hour, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (4.15 g, 41%).

1H-NMR (CDCl3) δ: 3,06 (1H, d, J=6.2 Hz), 3,91 (3H, s), 5,02 (2H, DD, J=5,8, and 11.4 Hz), 6,07 (1H, d, J=6.2 Hz), 6,94-7,00 (2H, m), 7.18 in-7,42 (N, m)of 7.96 (2H, d, J=8,4 Hz)

(2) Synthesis of methyl ester of 4-(2-benzyloxybenzyl)benzoic acid

In a stream of nitrogen triethylsilane of 2.27 ml, 13.5 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (of 1.52 ml, 11,88 mmol) was added to a solution of methyl ester 4-[(2-benzyloxyphenyl)-hydroxymethyl]benzoic acid (4.15 g, to 11.9 mmol) in acetonitrile (22.7 ml) at -40°C and the obtained mixed solution was stirred at the above-mentioned ones is the temperature for 1.5 hours, and then at 0°C for 30 minutes. To the mixture was added water and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10) to obtain specified in the connection header (2,39 g, 62%).

1H-NMR (CDCl3) δ: the 3.89 (3H, s), of 4.05 (2H, s), 5,02 (2H, d, J=5.8 Hz), 6,92 (2H, d, J=7.9 Hz), 7,12 and 7.36 (9H, m), to $ 7.91 (2H, d, J=8.0 Hz)

MS (ESI+): 333 [M+H]+

(3) Synthesis of methyl ester of 4-(2-hydroxybenzyl)benzoic acid

To a solution of methyl ester 4-(2-benzyloxybenzyl)benzoic acid (2,39 g, 7.19 mmol) in methanol (70 ml) was added catalyst a 20% palladium hydroxide (239 mg). The mixture was stirred in hydrogen atmosphere for five hours, then the catalyst was filtered. The solvent drove under reduced pressure to obtain specified in the connection header (1,16 g, 96%).

1H-NMR (CDCl3) δ: the 3.89 (3H, s), Android 4.04 (2H, s), was 4.76 (1H, s), 6,77 (1H, d, J=8.0 Hz), 6.89 in (1H, t, J=7,3 Hz), 7,13 (2H, m), 7,29 (2H, d, J=8,4 Hz), 7,94 (2H, d, J=8.0 Hz)

MS (ESI+): 243 [M+H]+

(4) Synthesis of [2-(4-methoxycarbonylbenzyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (1.10 g, 2.04 mmol) and Tr is butylphosphine (of 0.77 ml, a 3.06 mmol) was added to a solution of methyl ester 4-(2-hydroxybenzyl)benzoic acid (741,4 mg of 3.06 mmol) in toluene (6.9 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 526,5 mg of 3.06 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the connection header (429,0 mg, 28%).

1H-NMR (CD3OD) δ: 1,40 (1H, DD, J=12,0, 12.0 Hz), 1,65-of 1.74 (1H, m), 2,00-2,09 (1H, m), 3,43-3,59 (2H, m), of 3.84 (3H, s), of 4.00 (2H, s), 4,32-to 3.92 (8H, m)6,91 (1H, t, J=8.0 Hz),? 7.04 baby mortality-7,32 (25H, m), 7,87 (2H, d, J=8.0 Hz)

(5) Synthesis of [2-(4-methoxycarbonylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside

[2-(4-Methoxycarbonylbenzyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranose (38,1 mg, 0.05 mmol) was dissolved in a solvent mixture of methanol-THF (2:1) (1.5 ml) and the resulting mixture was added the catalyst of 20% palladium hydroxide (5 mg). The mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain ukazannoj is in the title compound (12.9 mg, 65%).

1H-NMR (CD3OD) δ: 0.89 as of 1.00 (1H, m), 1,47-of 1.62 (1H, m), 2,03-of 2.09 (1H, m), 3,16 is 3.23 (2H, m), 3,42-to 3.49 (2H, m), 3,51-a 3.87 (1H, m), of 3.95 (3H, s), 4,00-4,17 (2H, m), 4,19-to 4.23 (1H, m), 6.87 in (1H, d, J=7,4 Hz), 7,31 (1H, d, J=7,6 Hz), 7,12-7,20 (2H, m), 7,32 (2H, d, J=8,4 Hz), 7,88 (2H, d, J=8,4 Hz)

MS (ESI+): 403 [M+Na]+

Example 32

[2-(4-Carbamoylmethyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [2-(4-carboxybenzoyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside

In nitrogen atmosphere 5 N. aqueous sodium hydroxide solution (0.15 ml) was added at room temperature to a solution of [2-(4-methoxycarbonylbenzyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranose (100.0 mg, 0.13 mmol) in a solvent mixture of ethanol-THF (4:1) (1.5 ml) and the resulting mixed solution was stirred for 22 hours. Then to the reaction mixture was added with ice cooling 5 N. aqueous solution of hydrochloric acid to neutralize the mixture. The resulting mixture was extracted with methylene chloride and dried (sodium sulfate) and concentrated under reduced pressure to obtain specified in the connection header (for 91.3 mg, 94%).

1H-NMR (CDCl3) δ: 1,42 (1H, DDD, J=12,4, 12,4, and 12.4 Hz), 1,55-to 1.67 (1H, m), 2.00 in 2,04 (1H, m), 3,41-3,61 (2H, m), was 4.02 (2H, s), 4,35-to 3.92 (8H, m), 6,92 (1H, t, J=7,3 Hz), 7,05-7,32 (25H, m), 7,92 (2H, d, J=7,7 Hz)

MS (ESI+): 749 [M+H]+

(2) Synthesis of [2-(4-carboxybenzoyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside

In nitrogen atmosphere, monohydro is 1-hydroxybenzotriazole (9.0 mg, 0.07 mmol) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (12.0 mg, 0.07 mmol) was added to a solution of [2-(4-hydroxycarbonylmethyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside (45.0 mg, 0.06 mmol) in N,N-dimethylformamide (1.2 ml) at room temperature and the reaction mixture was stirred for one hour, then to the mixture under ice cooling was added aqueous ammonia (0.5 ml) and the mixture was stirred within 27 hours. The reaction mixture was concentrated under reduced pressure and was purified using TLC (eluent=methanol:methylene chloride (1:10)) to obtain specified in the connection header (39,1 g, 89%).

1H-NMR (CDCl3) δ: 1,31-1,49 (1H, m), 1,62 to 1.76 (1H, m), 1,96-of 2.08 (1H, m), 3,39-3,66 (2H, m), was 4.02 (2H, s), 4,33-4,96 (8H, m), 6,88-6,97 (1H, m),? 7.04 baby mortality-7,39 (25H, m), 7,54-to 7.61 (2H, m)

MS (ESI+): 748 [M+H]+

(3) Synthesis of [2-(4-carbamoylmethyl)phenyl]-5A-carb-β-D-glucopyranoside

To a solution (3 ml) of [2-(4-carbamoylmethyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside (39,1 mg, 0.05 mmol) in solvent methanol-THF (2:1) (3 ml) was added catalyst a 20% palladium hydroxide (5 mg). The obtained mixed solution was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified using TLC [eluent=methanol:methylene chloride (1:5)] to obtain specified in the header link is (19.2 g, 99%).

1H-NMR (CD3OD) δ: 0,92 (1H, DD, J=11,7, l1,7 Hz), 1,48-of 1.62 (1H, m), 1,96-of 2.08 (1H, m), 3,16-to 3.33 (4H, m), 3,42-3,59 (2H, m), 3,65-to 3.73 (1H, m), 3,93-4.26 deaths (3H, m), 6.87 in (1H, t, J=7,3 Hz), 7,02-7,21 (3H, m), 7,31 (2H, d, J=8,2 Hz), 7,74 (2H, d, J=8.1 Hz)

MS (ESI+): 388 [M+H]+

Retention time HPLC: 8.0 minutes

Example 33

[2-(4-N,N-Dimethylcarbamoyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of [2-(4-N,N-dimethylcarbamoyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside

In nitrogen atmosphere monohydrate, 1-hydroxybenzotriazole (9.0 mg, 0.07 mmol) and the hydrochloride of 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide (12.0 mg, 0.07 mmol) was added at room temperature to a solution of [2-(4-carboxybenzoyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside (45.0 mg, 0.06 mmol)obtained in Example 32, N,N-dimethylformamide (1.2 ml) and the reaction mixture was stirred for one hours. To the mixture was added with ice cooling an aqueous solution of N,N-dimethylamine (0.5 ml) and the mixture was stirred for 27 hours. The reaction mixture was concentrated under reduced pressure and was purified preparative TLC (eluent=methanol:methylene chloride=1:10) to obtain specified in the connection header (to 44.1 mg, 96%).

1H-NMR (CDCl3) δ: 1,42-of 1.52 (1H, m), 1,66-of 1.78 (1H, m), 2.05 is with 2.14 (1H, m), and 2.83 (3H, s), 3.04 from (3H, s), 3,44-3,68 (5H, m)to 3.99 (2H, s), 4,35-a 4.53 (1H, m), and 4.68 (2H, s), a 4.83-4,94 (3H, m)6,91 (1H, t, J=7,3 Hz),? 7.04 baby mortality was 7.36 (27H, m)

MS (ESI+): 776 [M+H]+

(2) inches [2-(4-N,N-dimethylcarbamoyl)phenyl]-5a-carb-β-D-glucopyranoside

To a solution in methanol-THF (2:1) (3 ml) of [2-(4-N,N-dimethylcarbamoyl)phenyl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside (to 44.1 mg, 0.06 mmol) was added catalyst a 20% palladium hydroxide (5 mg). The obtained mixed solution was stirred in an atmosphere of hydrogen for 24 hours and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified using TLC [eluent=methanol:methylene chloride (1:5)] to obtain specified in the connection header (20,1 mg, 87%).

1H-NMR (CD3OD) δ: 0,86-1,00 (1H, m), 1,45 is 1.58 (1H, m), 1,98 e 2.06 (1H, m), 2,95 (3H, s), 3,03 (3H, s), 3,13-3,49 (5H, m), 3,62-3,68 (1H, m), 3,88-is 4.21 (3H, m)6,91 (1H, t, J=7.2 Hz), 6,98-to 7.15 (3H, m), 7,26 (4H, s)

MS (ESI+): 416 [M+H]+

Retention time HPLC: 8.9 minutes

Example 34

[2-(4-Ethoxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-(4-ethoxybenzyl)phenol

In a stream of nitrogen a solution of n-utility in hexane (2,71 M, 3.8 ml) was added dropwise at -78°C to a solution of 1-benzyloxy-2-bromine benzol (2.5 g, 9.5 mmol) in THF (90 ml) and the resulting mixed solution was stirred at the same temperature for 30 minutes. To this mixture was added dropwise at -78°C solution of 4-ethoxybenzaldehyde (1,29 ml of 1.86 mmol) in THF (30 ml). The reaction mixture was stirred at the same temperature for two hours, then to the mixture was added water and the mixture was extracted with ethylacetophenone layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)]. To a solution in methanol (26,8 ml) of the obtained crude product was added catalyst a 20% palladium hydroxide (147 mg), and then to the mixture was added 36% HCl solution (0.4 ml). The mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (828,1 mg, 38%).

1H-NMR (CDCl3) δ: of 1.39 (3H, t, J=7.0 Hz), 3,93 (2H, s)to 3.99 (2H, square, J=7,0 Hz), 6,77-of 6.90 (4H, m), 7,09-7,14 (4H, m)

(2) Synthesis of [2-(4-ethoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added under ice cooling to a solution of 2-(4-ethoxybenzyl)phenol (319,6 mg, 1.4 mmol) in toluene (3.2 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained statecapital column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in methanol (5 ml), the mixture was added the catalyst of 20% palladium hydroxide (56 mg) and the reaction mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the connection header (133,5 mg, 36%).

1H-NMR (CD3OD) δ: 0,89-1,03 (1H, m)of 1.35 (3H, t, J=7,1 Hz), 1,48-of 1.62 (1H, m), 2,02-2,11 (1H, m), 3,18-to 3.33 (3H, m)to 3.35 (2H, s), 3,44-to 3.52 (2H, m), 3,68-3,74 (1H, m), 3,81-was 4.02 (4H, m), 4,13-to 4.23 (1H, m), 6,74-6,87 (4H, m), 6,99-7,17 (4H, m)

MS (ESI+): 411 [M+Na]+

Retention time HPLC: 11.4 minutes

Example 35

[2-(4-Deformational)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-(4-deformational)phenol

In a stream of nitrogen a solution of n-utility in hexane (2,71 M, 3.8 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2.5 g, 9.5 mmol) in THF (90 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C solution of 4-deformationally (1.23 ml of 1.86 mmol) in THF (30 ml). The reaction mixture was stirred at the same temperature for two hours, then to the mixture was added water and the mixture was extracted with ethyl acetate, the m The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent-ethyl acetate:n-hexane (1:5)] to obtain the crude product. To a solution of the crude product in methanol (26,8 ml) was added catalyst a 20% palladium hydroxide (147 mg), and then to the mixture was added concentrated hydrochloric acid (0.4 ml). The obtained mixed solution was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain wannago in the connection header (1,03 g, 42%).

1H-NMR (CDCl3) δ: of 3.97 (2H, s), 6,46 (1H, t, J=74,4 Hz), 6,77 (1H, d, J=8.0 Hz), 6.87 in-6,91 (1H, t, J=7,3 Hz), 7,03 (2H, d, J=8,4 Hz), 7,09-to 7.15 (2H, m), 7,21 (2H, d, J=8.0 Hz)

(2) Synthesis of [2-(4-deformational)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added to a solution of 2-(4-di-formicoxenini)phenol (350,0 mg, 1.4 mmol) in toluene (3.2 ml) under ice cooling, and then to the mixture were added when the specified temperature is re tetramethyldisiloxane (TMAD, 239 mg, of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in methanol (5 ml), the mixture was added the catalyst of 20% palladium hydroxide (69 mg)obtained mixed solution was stirred in an atmosphere of hydrogen for 24 hours and the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the connection header (153,1 mg, 40%).

1H-NMR (CD3OD) δ: 0,87-a 1.01 (1H, m), 1,48-of 1.62 (1H, m), 2,01-2,11 (1H, m), 3,17-to 3.34 (2H, m), 3.43 points-of 3.54 (2H, m), 3,67-to 3.73 (1H, m), of 3.96 (2H, DD, J=22,9, of 14.7 Hz), 4,14-4.26 deaths (1H, m), 6,72 (1H, t, J=74,5 Hz), 6,83-of 7.25 (8H, m)

MS (ESI+): 433 [M+Na]+

Retention time HPLC: 11.6 minutes

Example 36

[2-(4-tert-butylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside (1) Synthesis of (2-benzyloxyphenyl)-(4-tert-butylphenyl)methanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 5,65 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (3,3 g, 12.5 mmol) in THF (126 ml) at -78°C and the obtained mixed solution was stirred PR the specified temperature for 30 minutes. To this solution was added at -78°C solution of 4-tert-butylbenzaldehyde (1.68 g, 10.4 mmol) in THF (42 ml). The reaction mixture was stirred at the same temperature for one hour, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (2.17 g, 60%).

1H-NMR (CDCl3) δ: of 1.32 (9H, s), 2,86 (1H, users), 5,02 (2H, s), 6,03 (1H, s), 6,03-7,00 (2H, m), 7,13-7,39 (11H, m)

(2) Synthesis of 2-(4-tert-butylbenzyl)phenol

To a solution of (2-benzyloxyphenyl)-(4-tert-butylphenyl)methanol (2.17 g, 6.26 mmol) in methanol (27 ml) was added catalyst a 20% palladium hydroxide (217 mg), and then to the mixture was added 2 n HCl solution (0,52 ml). The mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept off and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compound (1.3 g, 86%).

1H-NMR (CDCl3) δ: of 1.29 (9H, s), of 3.96 (2H, s)and 4.65 (1H, s), 6.75 in-6,91 (2H, m), 7,09-to 7.32 (6H, m)

(3) Synthesis of [2-(4-tert-butylbenzyl)phenyl]-5a-carb-β-D-g is unoperated

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added under ice cooling to a solution of 2-(4-tert-butylbenzyl)phenol (334 mg, of 1.39 mmol) in toluene (2 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a solvent mixture of methanol-THF (1:1) (12 ml) and the resulting mixture was added the catalyst of 20% palladium hydroxide (60 mg) and the mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (57 mg, 15%).

1H-NMR (CD3OD) δ: 0,89-a 1.01 (1H, m)of 1.29 (9H, s), 1,53-to 1.59 (1H, m), 2,04-2,11 (1H, m), 3,19-to 3.34 (2H, m), 3,45-3,51 (2H, m), 3,71 (1H, DD, J=10,8, and 4.5 Hz), 3,95 (2H, m), 4,19 (1H, m), at 6.84 (1H, m), 7,01-7,17 (5H, m), 7,26-7,28 (2H, m)

MS (ESI+): 401 [M+H]+

Retention time HPLC: 13.7 minutes

Note the R 37

[2-(4-Methylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-p-trimethanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 5,65 ml) was added dropwise at -78°C to a solution of 1-benzyloxy-2-bromine benzol (3.3 grams, 12,54 mmol) in THF (126 ml) and the mixture was stirred at the same temperature for 30 minutes. To this mixture was added at -78°C solution of 4-methylbenzaldehyde (1.28 g, 10.6 mmol) in THF (42 ml). The reaction mixture was stirred at the same temperature for one hour, then to the mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (2.3 g, 71%).

1H-NMR (CDCl3) δ: of 2.33 (3H, s), 2,87 (1H, s), 5,02 (2H, s), 6,03 (1H, s), 6,09-6,99 (2H, m), 7,09-7,34 (11H, m)

(2) Synthesis of 2-(4-methylbenzyl)phenol

To a solution of (2-benzyloxyphenyl)-p-trimethanol (1.5 g, 4,43 mmol) in methanol (27 ml) was added catalyst a 20% palladium hydroxide (150 mg), and then to the mixture was added 2 n HCl solution (0,37 ml). The mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent of Otho the Yali under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compound (617 mg, 70%).

1H-NMR (CDCl3) δ: 1.55V (3H, s), of 3.95 (2H, s)and 4.65 (1H, s), 6.75 in-6, 90 (2H, m), 7,09-of 7.25 (6H, m)

(3) Synthesis of [2-(4-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) was added under ice cooling to a solution of 2-(4-methylbenzyl)phenol (275 mg, of 1.39 mmol) in toluene (2 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 239 mg of 1.39 mmol). The reaction mixture was stirred for 20 hours while gradually raising its temperature to room temperature. The reaction mixture was concentrated under reduced pressure and the obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)]. The crude product was dissolved in a solvent mixture of methanol-THF (1:1) (8 ml), the mixture was added the catalyst of 20% palladium hydroxide (44 mg), the mixture was stirred in an atmosphere of hydrogen for 24 hours and the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (20 mg, 6%).

1H-NMR (CD3OD) δ: from 0.84 to 0.97 (1H, m), 1,44-2,03 (1H, m), 1,96-2,03 (1H, m), 2,22 (3H, s), 3,13-3,30 (2H, m), 3,39-of 3.46 (2H, m)to 3.64 (1H, DD, J=10,8, 45 Hz), of 3.95 (2H, m), of 4.12 (1H, m), 6,76-for 6.81 (1H, m), 6,92-7,03 (5H, m), 7,06-7,11 (2H, m)

MS (ESI+): 381 [M+Na]+

Retention time HPLC: 11.4 minutes

Example 38

[2-(4-Methoxybenzyl)-5-triptorelin-3-yl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 3-benzyloxy-2-(4-methoxybenzyl)-5-triptorelin

To a solution of (3-benzyloxy-5-triptorelin-2-yl)-(4-methoxyphenyl)methanone (220,2 mg of 0.56 mmol), synthesized by the method described in International Publication No. WO04/007517, and triethylsilane (of 1.34 ml, to 8.41 mmol) in dichloromethane (1.1 ml) was added at 0°C triperoxonane acid (3 ml) in a stream of nitrogen for five minutes. The reaction mixture was stirred at the same temperature in the course of 6.75 hours and then to the mixture was added triethylsilane (0.9 ml, 5,61 mmol). The reaction mixture was stirred at the same temperature for x 16.75 hours and then concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the connection header (108,8 mg, 51%).

1H-NMR (CDCl3) δ: with 3.79 (3H, s), of 3.96 (2H, s), 5,04 (2H, s), PC 6.82 (2H, d, J=8.6 Hz), 7,11 (2H, d, J=8.6 Hz), 7,16 (1H, s), 7,30-7,41 (5H, m)

(2) Synthesis of 2-(4-methoxybenzyl)-5-triptorelin-3-ol

To a solution of (3-benzyloxy-2-(4-methoxybenzyl)-5-triptorelin (170,5 mg, 0.45 mmol) in dichloromethane (4.5 ml) was added at -78°C in a stream AZ is the solution of the complex tribromide boron-dimethyl sulfide in dichloromethane (of 0.47 ml, 0.47 mmol). The reaction mixture was stirred at the same temperature for five minutes and then at 0°C for 11 hours. To the reaction mixture were added water and the resulting mixture was extracted with methylene chloride. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride and dried (anhydrous sodium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (117,0 mg, 90%).

1H-NMR (CDCl3) δ: of 3.80 (3H, s), of 3.97 (2H, s), 4,47 (1H, s), 6.87 in (2H, d, J=8.6 Hz), 6,98 (1H, s), 7,19 (2H, d, J=8.6 Hz)

(3) Synthesis of [2-(4-methoxybenzyl)-5-triptorelin-3-yl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside

In a stream of nitrogen 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (146 mg, 0.27 mmol) and tributylphosphine (0.10 ml, 0.41 mmol) was added under ice cooling to a solution of 2-(4-methylbenzyl)-5-triptorelin-3-ol (117 mg, 0.41 mmol) in toluene (0,85 ml), and then to the mixture was added at the same temperature tetramethyldisiloxane (TMAD, 70 mg, 0.41 mmol). The reaction mixture was stirred at room temperature for a period of 18.5 hours. The reaction mixture was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10 to 1:8)]. P the obtained product was purified preparative TLC [eluent=ethyl acetate:n-hexane (1:8)] to obtain specified in the connection header (to 47.2 mg).

1H-NMR (CDCl3) δ: 1,56-of 1.80 (2H, m), 1,96-2,10 (1H, m), 3,40-3,70 (5H, m in), 3.75 (3H, s), of 3.96 (2H, s), 3.96 points-of 4.16 (1H, m), of 4.44 (2H, s), a 4.53 (1H, d, J=11,0 Hz), 4,70-5,00 (5H, m), 6,79 (2H, d, J=8.6 Hz), 7,06-7,38 (23H, m)

(4) Synthesis of [2-(4-methoxybenzyl)-5-triptorelin-3-yl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen [2-(4-methoxybenzyl)-5-triptorelin-3-yl]-2,3,4,6-Tetra-O-benzyl-5a-carb-β-D-glucopyranoside (45,2 mg, 0,056 mmol) was dissolved in methylene chloride (0.5 ml) and the resulting mixture was added under ice cooling dimethyldisulfide (0,145 ml, 3.35 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0,07 ml of 0.56 mmol). The reaction mixture was stirred at the same temperature for five minutes and then at room temperature for 19 hours, then to the mixture was added under ice cooling a saturated aqueous sodium hydrogen carbonate solution and water and was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous sodium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified using TLC [eluent=n-hexane:acetone (1:1)] to obtain specified in the connection header (12,2 mg, 49%).

1H-NMR (CD3OD) δ: 1,15-1,35 (1H, m), 1,40-of 1.65 (1H, m), 1,95-2,15 (1H, m), 3,15-to 3.35 (2H, ra), 3,35-of 3.60 (2H, m), 3,65-of 3.80 (1H, m in), 3.75 (3H, m), 3,90-4,06 (1H, m)to 4.01 (2H, m), at 6.84 (2H, d, J=8,3 Hz), 7,16 (2H, d, J=8,3 Hz), 7,40 (1H, s)

MS (ESI+): 448 [M]+

Time to hold the air traffic management HPLC: 12.4 minutes

Example 39

[3-Methoxy-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of benzyl ether of 2-benzyloxy-6-methoxybenzoic acid

With stirring, a mixture of 6-methoxysilanes acid (5,07 g to 30.15 mmol) and sodium hydride (60% wt./wt., to 3.02 g, 75,38 mmol) to the mixture under ice cooling was added DMF (30 ml). The obtained mixed solution was stirred at the same temperature for 10 minutes, then to the mixture was added within 5 minutes benzylbromide (of 8.95 ml, 75,38 mmol) and the reaction mixture was stirred at the same temperature for 30 minutes and at room temperature for 2.5 hours. To the reaction mixture was added under ice cooling a saturated aqueous solution of ammonium chloride and water and the mixture was extracted with simple ether. The organic layer was washed with water and saturated aqueous ammonium chloride and was dried (anhydrous sodium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10 to 1:5)] to obtain specified in the connection header (6,24 g, 59%).

1H-NMR (CDCl3) δ: 3,81 (3H, s), to 5.08 (2H, s), to 5.35 (2H, s), 6,55 (1H, d, J=5,9 Hz), to 6.58 (1H, d, J=5,9 Hz), 7,15 was 7.45 (11H, m)

(2) (2-Benzyloxy-6-methoxyphenyl)methanol

In a stream of nitrogen to a suspension of sociallyengaged (0.88 g, 23,14 mmol) vProTM ether (35 ml) was added at room temperature during 15 minutes a solution of benzyl ester 2-benzyloxy-6-methoxybenzoic acid (6.2 g, 17,80 mmol) in a simple ether (20 ml). The reaction mixture was stirred for two hours when heated to the boiling temperature under reflux. To the reaction mixture under ice cooling was added dropwise ethyl acetate (2 ml), and then to the mixture was added dropwise a saturated aqueous solution of Rochelle salt (20 ml) and the mixture was stirred at room temperature for 20 hours. The reaction mixture was subjected to filtration through celite, the filtrate was added a saturated aqueous solution of Rochelle salt (15 ml) and the mixture was extracted with simple ether. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous sodium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=simple ether:n-hexane (1:1)] to obtain specified in the connection header and 4.75 g, 100%).

1H-NMR (CDCl3) δ: 2,48 (1H, t, J=6.8 Hz), 3,85 (3H, s), 4,84 (2H, d, J=6.8 Hz), 5,10 (2H, s), to 6.58 (1H, d, J=8,4 Hz), 6,62 (1H, d, J=8,2 Hz), 7,20 (1H, DD, J=8,4, 8,2 Hz), 7,28-7,47 (5H, m)

(3) Synthesis of (2-benzyloxy-6-methoxyphenyl)-(4-methoxyphenyl)methanol

In a stream of nitrogen to a solution of (2-benzyloxy-6-methoxyphenyl)-methanol (3,52 g, 14,41 mmol) and N-oxide N-methylmorpholine (NMO, 2,53 g of 21.61 mmol) in dichloromethane (14,5 ml) was cooled in a water bath and the resulting mixture was added perruthenate Tetra-n-Propylamine (TPAP, 152 is g, 0.43 mmol). The reaction mixture was stirred for 20 minutes at the same temperature and at room temperature for about 1.75 hours, and then subjected to filtration through celite and the solvent drove away under reduced pressure. The obtained residue was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane(1:3 → 1:2,5)]. The compound obtained was dissolved in THF and cooled in a water bath and the resulting mixture was added dropwise in a stream of nitrogen to a solution of 4-methoxyphenylacetamide in THF (0.5 M, 30,3 ml). The reaction mixture was stirred at room temperature for 1.25 hours, then to the mixture was added at room temperature, a saturated aqueous solution of ammonium chloride and the mixture was extracted with simple ether. The organic layer was washed with a saturated aqueous solution of ammonium chloride and was dried (anhydrous sodium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane(1:4 →1:3,5)] obtaining specified in the connection header (3,66 g, 72%).

1H-NMR (CDCl3) δ: of 3.78 (3H, s), 3,81 (3H, s), 4,28 (1H, d, J=11.7 Hz), 4,99 (1H, d, J=11.5 Hz), is 5.06 (1H, d, J=11.5 Hz), 6,33 (1H, d, J=11.7 Hz), is 6.61 (1H, d, J=7,6 Hz), only 6.64 (1H, d, J=7,6 Hz), to 6.80 (2H, d, J=8.7 Hz), 7,10-7,40 (8H, m)

(4) 3-Methoxy-2-(4-methoxybenzyl)phenol

To a solution of (2-benzyloxy-6-methoxyphenyl the)-(4-methoxyphenyl)-methanol (2,13 g, between 6.08 mmol) in methanol (50 ml) was added catalyst a 20% palladium hydroxide (0.32 g) and then to the mixture was added 2 n HCl solution (1.8 ml). The reaction mixture was stirred in an atmosphere of hydrogen for 24 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (1.31 g, 89%).

1H-NMR (CDCl3) δ: 3,76 (3H, s), 3,82 (3H, s), 3,98 (2H, s), of 4.67 (1H, s), of 6.45 (1H, d, J=8.1 Hz), of 6.52 (1H, d, J=8,2 Hz), 6,79 (1H, d, J=8.6 Hz), 7,07 (1H, DD, J=8,1, 8,2 Hz), 7,17 (1H, d, J=8.6 Hz)

(5) Synthesis of [3-methoxy-2-(4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen to a solution of 3-methoxy-2-(4-methoxybenzyl)phenol (343 mg, of 1.40 mmol) in a solvent mixture of toluene-THF (2.5 ml toluene, THF 0.3 ml) was added under ice cooling 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (504 mg, of 0.94 mmol) and tributylphosphine (0,35 ml of 1.40 mmol) and the resulting mixture was added at the same temperature tetramethyldisiloxane (TMAD, 242 mg of 1.40 mmol). The reaction mixture was stirred for 1.25 hours with ice cooling and then at room temperature for 22 hours. The reaction mixture was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane(1:10→1:5)]. The crude product was dissolved in CME is this solution of methanol-THF (1:4) (10 ml), to the mixture was added the catalyst of 20% palladium hydroxide (94 mg) and the resulting mixed solution was stirred in an atmosphere of hydrogen for 5 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol(15:1 → 10:1)] obtaining specified in the title compound (121 mg, 32%).

1H-NMR 0,85-1,05 (1H, m), 1,40-of 1.65 (1H, m), 1,95-2,15 (1H, m), 3,10-3,30 (2H, m), 3,40-3,55 (2H, m), 3,60 of 3.75 (1H, m), 3,71 (3H, s), with 3.79 (3H, s)to 3.92 (2H, s), 4,05-of 4.25 (1H, m), 6,59 (1H, d, J=8,2 Hz), 6,65 to 6.75 (3H, m), 7,05-to 7.15 (3H, m)

MS (ESI+): 405 [M+H]+

Retention time HPLC: 10.6 minutes

Example 40

[2-(4-Methoxybenzyl)-3-were]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (2-benzyloxy-6-methoxyphenyl)methanol

In a stream of nitrogen to a suspension of sociallyengaged (0,82 g of 21.50 mmol) in a simple ether (30 ml) was added at room temperature over 10 minutes a solution of ethyl ester of 2-benzyloxy-6-methylbenzoic acid (4,47 g, 16,54 mmol) in a simple ether (15 ml). The reaction mixture was stirred under heating up to the boiling temperature under reflux for one hour. To the reaction mixture under ice cooling was added dropwise ethyl acetate (2 ml), and then to the mixture was added dropwise a saturated aqueous solution of Rochelle salt (20 ml) and the mixture was stirred pikantnoi temperature for one hour. The reaction mixture was subjected to filtration through celite. To the filtrate was added saturated aqueous Rochelle's salt solution (10 ml) and the mixture was extracted with simple ether. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous sodium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the connection header (3,84 g, 100%).

1H-NMR (CDCl3) δ: 2,20 (1H, d, J=6.6 Hz), is 2.40 (3H, s), 4,79 (2H, d, J=6.6 Hz), 5,11 (2H, s), 6,83 (2H, d, J=7.9 Hz), to 7.15 (1H, t, J=7.9 Hz), 7,25 is 7.50 (5H, m)

(2) Synthesis of 2-benzyloxy-6-methylbenzaldehyde

In a stream of nitrogen to a solution of (2-benzyloxy-6-methoxyphenyl)-methanol (of 3.46 g, 15,16 mmol) and N-oxide N-methylmorpholine (NMO, 2.66 g, 22,73 mmol) in dichloromethane (10 ml) was cooled in a water bath and the resulting mixture was added perruthenate Tetra-n-Propylamine (TPAP, 152 mg, 0.43 mmol). The reaction mixture was stirred at the same temperature for 1.75 hours, and then subjected to filtration through celite and the solvent drove in under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (is 3.08 g, 90%).

1H-NMR (CDCl3) δ: 2,59 (3H, s), 5,16 (2H, s), PC 6.82 (1H, d, J=7,3 Hz), make 6.90 (1H, d, J=8,4 Hz), 7,25 is 7.50(6H, m), of 10.73 (1H, s)

(3) Synthesis of (2-benzyloxy-6-were)-(4-methoxyphenyl)methanol

In a stream of nitrogen a solution of 2-benzyloxy-6-methoxybenzaldehyde (is 3.08 g of 13.6 mmol) in THF (10 ml) was cooled in a water bath and the resulting mixture was added dropwise a solution of 4-methoxyphenylacetamide THF (0.5 M, 30,3 ml). The obtained mixed solution was stirred at room temperature for about 1.75 hours, then to the mixture was added under ice cooling a saturated aqueous solution of ammonium chloride and the mixture was extracted with simple ether. The organic layer was washed with a saturated aqueous solution of ammonium chloride and was dried (anhydrous sodium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane(1:6→1:5)] obtaining specified in the connection header and 4.75 g, 100%).

1H-NMR (CDCl3) δ: of 2.38 (3H, s), of 3.80 (3H, s), 4.09 to (1H, d, J=11.2 Hz), 4,88 (1H, d, J=11.5 Hz), 5,00 (1H, d, J=11.5 Hz), 6,03 (1H, d, J=11.2 Hz), 6.75 in-6,90 (4H, m), 6.90 to-7,05 (2H, m), 7,10-to 7.35 (6H, m)

(4) Synthesis of 2-(4-methoxybenzyl)-3-METHYLPHENOL

To a solution of (2-benzyloxy-6-were)-(4-methoxyphenyl)-methanol (2,39 g, 7,15 mmol) in methanol (50 ml) was added catalyst a 20% palladium hydroxide (0.36 g), then to the mixture was added 36% HCl solution (0,36 ml). The mixture was stirred in hydrogen atmosphere for 11 hours, then the catalyst Hotfile revival. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (1.40 g, 86%).

1H-NMR (CDCl3) δ: 2,28 (3H, s), 3,76 (3H, s)to 3.99 (2H, s), br4.61 (1H, s), to 6.67 (1H, d, J=8.1 Hz), 6,70-6,85 (3H, m), 6,95-to 7.15 (3H, m)

(5) Synthesis of [2-(4-methoxybenzyl)-3-were]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen to a solution of 2-(4-methoxybenzyl)-3-METHYLPHENOL (318 mg, of 1.39 mmol) in a solvent mixture of toluene-THF (toluene 1 ml THF, 0.1 ml) was added under ice cooling 2,3,4,6-Tetra-O-benzyl-5A-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) and the resulting mixture was added at the same temperature tetramethyldisiloxane (TMAD, 242 mg of 1.40 mmol). The reaction mixture was stirred for 10 minutes under ice cooling and then at room temperature for 23 hours. The reaction mixture was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane(1:7 → 1:6)]. The crude product was dissolved in a solvent mixture of methanol-THF (1:3) (4 ml), the mixture was added the catalyst of 20% palladium hydroxide (66 mg) and the resulting mixed solution was stirred in hydrogen atmosphere for 6.5 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and obtained the residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (55 mg, 15%).

1H-NMR (CD3OD) δ: 0,85-1,05 (1H, m), 1,45-of 1.65 (1H, m), 2.00 in to 2.15 (1H, m), of 2.21 (3H, s), 3,15-3,30 (2H, m), 3,40-3,55 (2H, m), 3,65 of 3.75 (1H, m), and 3.72 (3H, s), of 3.94 (1H, d, J=15,0 Hz)4,06 (1H, d, J=15,0 Hz), 4,05-4,20 (1H, m), 6,70-to 6.80 (3H, m)6,91 (1H, d, J=8,2 Hz), 6,95-7,10 (3H, m)

MS (ESI+): 411 [M+Na]+

Retention time HPLC: 11.2 minutes

Example 41

[2-(3-Fluoro-4-methoxybenzyl)phenyl]-5a-carb-α-D-glucopyranosid

(1) Synthesis of (2-benzyloxyphenyl)-(3-fluoro-4-methoxyphenyl)-methanol

In a stream of nitrogen a solution of n-utility in hexane (1,54 M, 6,79 ml) was added dropwise to a solution of 1-benzyloxy-2-bromine benzol (2.5 g, 9.50 mmol) in THF (30 ml) at -78°C and the mixture was stirred at the same temperature for 30 minutes. To this solution was added dropwise at -78°C solution of 3-fluoro-4-methoxybenzaldehyde (1,32 g, 8,56 mmol) in THF (8 ml). The mixture was stirred at the same temperature for one hour, then to the mixture was added saturated aqueous solution of ammonium chloride, the mixture was extracted with ethyl acetate, the organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (2,79 g, 96%).

1H-NMR (CDCl3) δ: 2,92 (1H, d, J=5.8 Hz), a 3.87 (3H, s), of 5.03 (2H, s), 5,98 (1H, d, J=6.0 Hz), 6,85-710 (5H, m), 7,21-to 7.35 (7H, m)

(2) Synthesis of 2-(3-fluoro-4-methoxybenzyl)phenol

To a solution of (2-benzyloxyphenyl)-(3-fluoro-4-methoxyphenyl)-methanol (1.50 g, 4,43 mmol) in methanol (29 ml) was added catalyst a 20% palladium hydroxide (150 mg), and then to the mixture was added 2 n HCl solution (2 ml). The mixture was stirred in hydrogen atmosphere for 15 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (0.95 g, 92%).

1H-NMR (CDCl3) δ: of 3.85 (3H, s), 3,91 (2H, s), 4,69 (1H, users), 6,77 (1H, DD, J=1,1, 8,O Hz), 6,84-6,97 (4H, m), 7,09-7,16 (2H, m)

(3) Synthesis of [2-(3-fluoro-4-methoxybenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen to a solution of 2-(3-fluoro-4-methoxybenzyl)phenol (323 mg, of 1.39 mmol) in toluene (3 ml) was added under ice cooling 2,3,4,6-Tetra-O-benzyl-5a-carb-α-D-glucopyranose (500 mg, of 0.93 mmol) and tributylphosphine (0.35 ml, of 1.39 mmol) and the resulting mixture was added at the same temperature tetramethyldisiloxane (TMAD, 242 mg of 1.40 mmol). The reaction mixture was stirred for 40,5 hours while gradually raising its temperature to room temperature. The reaction mixture was treated with column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:6)]. The crude product is dissolved in a solvent mixture of methanol-THF (1:2) (6 ml), to the mixture was added the catalyst of 20% palladium hydroxide (65 mg) and the mixture was stirred in hydrogen atmosphere for two hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (78 mg, 21%).

1H-NMR (CD3OD) δ: 0,85-1,05 (1H, m), 1,40-of 1.65 (1H, m), 1,95-2,15 (1H, m), 3,35-of 3.60 (2H, m), 3,60-4,00 (3H, m), 3,81 (3H, s), 4,05-of 4.25 (1H, m), 6,70-7,20 (7H, m)

MS (ESI+): 392 [M]+

Retention time HPLC: 10.7 minutes

Example 42

[4-(4-Cyclopropylmethyl)pyridine-3-yl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 3-(2-trimethylsilylamodimethicone)pyridine

Sodium hydride (3,85 g, 96.3 mmol) was washed with hexane and the resulting mixture was added dimethoxyethane (90 ml). To the resulting mixture under ice cooling was added within 10 minutes 3 hydroxypyridine (equal to 4.97 g, 52,3 mmol) and the reaction mixture was stirred for 10 minutes, then to the mixture was added under ice cooling for 25 minutes 2-(trimethylsilyl)ethoxymethylene (10.0 ml, of 56.5 mmol). The reaction mixture was stirred at room temperature for a period of 14.5 hours. To the reaction mixture under ice cooling was added water, the mixture was extracted with simple ether and the organic layer was dried over anhydrous sulfate MAGN what I was concentrated under reduced pressure. The obtained residue was purified using flash column-chromatography on silica gel [eluent=n-hexane:ethyl acetate (3:1)] to obtain specified in the header of the product (10.8 g, 92%).

1H-NMR (CDCl3) δ: 0,00 (9H, s), 0,93-0,98 (2H, m), of 3.73-with 3.79 (2H, m), of 5.24 (2H, s), 7.18 in-of 7.23 (1H, m), 7,34-7,38 (1H, m), of 8.25 (1H, DD, J=4,7, and 1.4 Hz), 8,40 (1H, DD, J=3,0, 0.6 Hz)

(2) Synthesis of (4-cyclopropylmethyl)-[3-(2-trimethyl-similarexperience)pyridine-4-yl]methanol

In a stream of nitrogen to a solution of tert-utility in n-pentane (1,47 M, of 6.20 mmol) was added dropwise to a solution of 3-(2-trimethylsilylamodimethicone)pyridine (1.77 g, 7.85 mmol) in anhydrous THF (31 ml) at -78°C for 25 minutes. The mixture was stirred at -70°C for one hour, then to the mixture was added over 25 minutes to a solution of 4-cyclopropylbenzene (1,49 g, 10,19 mmol) in a simple ether (10 ml) and the reaction mixture was stirred at -70°C for two hours and at room temperature for two hours. To the reaction mixture were added saturated aqueous solution of ammonium chloride, the mixture was extracted with simple ether and the organic layer was dried over anhydrous magnesium sulfate. After filtering, the solvent is kept under reduced pressure and the obtained residue was purified using flash column-chromatography on silica gel [eluent=n-hexane:ethyl acetate (2:1)] to obtain specified in the header of the product (2.17 g, 74%).

1H-NMR (CDCl3) is: -0,04 (9H, C), and 0.61-0,66 (2H, m), 0,84-0,96 (4H, m), 1,79-1,90 (1H, m), 3,48-3,59 (2H, m), 5,13 (2H, DD, J=22,8, 6.9 Hz), 6,00 (1H, s), 6,97-6,99 (2H, m), 7,20-of 7.23 (2H, m), of 7.48 (1H, d, J=4.9 Hz), 8,18 (1H, d, J=4,9 Hz), of 8.27 (1H, s)

(3) Synthesis of (4-cyclopropylmethyl)-[3-(2-(trimethylsilyl)-ethoxyethoxy)pyridine-4-yl]methanone

In a stream of nitrogen periodinane dessa-Martin (2,71 g, to 6.39 mmol) was added to a solution of (4-cyclopropylmethyl)-[3-(2-trimethylsilylamodimethicone)pyridine-4-yl]methanol (2.17 g of 5.84 mmol) in methylene chloride (31 ml) and the reaction mixture was stirred at room temperature for 1.5 hours. Then to the reaction mixture were added periodinane dessa-Martin (0.27 g, 0.64 mmol) and the resulting mixture was stirred for 1.5 hours. Insoluble substances were filtered off and the filtrate was washed with a saturated aqueous solution of sodium bicarbonate and a saturated solution of sodium chloride and dried over anhydrous magnesium sulfate, then the solvent is kept at reduced pressure. The obtained residue was purified using chromatography with silica gel for separation Amin [eluent=ethyl acetate:n-hexane (1:1)] to obtain specified in the header of the product (1,96 g, 91%),

1H-NMR (CDCl3) δ: -0,04 (9H, s), 0,76-0,90 (4H, m), of 1.05 to 1.12 (2H, m), 1,92-to 1.98 (1H, m), 3,56-3,62 (2H, m)to 5.17 (2H, s), 7,09-7,13 (2H, m), 7,19-7,21 (1H, m), to 7.67-7,71 (2H, m), 8,40 (1H, d, J=4,67 Hz), 8,65 (1H, s)

(4) Synthesis of (4-cyclopropylmethyl)-(3-hydroxypyridine-4-yl)methanone

Monohydrate p-toluensulfonate acid (3.03 g, 15,9 mm is l) was added to a solution of (4-cyclopropylmethyl)-[3-(2-trimethylsilylamodimethicone)pyridine-4-yl]methanone (1,96 g, and 5.30 mmol) in THF (49 ml) and the resulting mixed solution was stirred at 65°C for one hour. The reaction mixture was cooled to room temperature, was added a saturated aqueous solution of sodium bicarbonate, the mixture was extracted with simple ether and the organic layer was dried over anhydrous magnesium sulfate. After filtering, the solvent is kept under reduced pressure and the obtained residue was purified using flash column-chromatography on silica gel [eluent=n-hexane:ethyl acetate (2:3)] to obtain specified in the header of the product (1.10 g, 87%).

1H-NMR (CDCl3) δ: 0,80-0,86 (2H, m), 1,09 is 1.16 (2H, m), 1,97-2,03 (1H, m), 7.18 in-7,22 (2H, m), 7,42 (1H, DD, J=5,2, 0.6 Hz), 7,63-to 7.68 (2H, m), 8,24 (1H, d, J=5,2 Hz), 8,59 (1H, d, J=0.6 Hz), of 11.15 (1H, s)

(5) Synthesis of (4-cyclopropylmethyl)-[3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)pyridine-4-yl]methanone

In a stream of nitrogen diisopropylsalicylic (0,14 ml, to 0.72 mmol) was slowly added dropwise to a mixture of (4-cyclopropylmethyl)-(3-hydroxypyridine-4-yl)methanone (0.18 g, of 0.74 mmol), (1S,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxypyrrolidine (0.20 g, of 0.37 mmol), triphenylphosphine (0,19 g of 0.74 mmol) and toluene (1.3 ml) under cooling with ice. The reaction mixture was stirred at room temperature for three hours, then the solvent is kept under reduced pressure and the resulting residue was purified through a column of flash is-chromatography on silica gel [eluent=n-hexane:ethyl acetate (2:3)] to obtain specified in the header of the product (0.20 g, 71%).

1H-NMR (CDCl3) δ: 0,67-to 0.73 (2H, m), 1.00 and was 1.06 (2H, m), of 1.39 to 1.47 (1H, m), 1,81-of 1.88 (1H, m), 2,09-of 2.16 (1H, m), 3,37-to 3.58 (5H, m), 4,36-4,51 (6H, m), 4,76-a 4.86 (3H, m), 6,98-7,07 (4H, m), 7,13-7,35 (19H, m), 7,62-7,66 (2H, m,), a 8.34 (1H, d, J=4.9 Hz), 8,54 (1H, s)

(6) Synthesis of (4-cyclopropylmethyl)-[3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)pyridine-4-yl]methanol

Borohydride sodium (40 mg, 1.06 mmol) was added to a solution of (4-cyclopropylmethyl)-[3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)pyridine-4-yl]methanone (0.20 g, 0.26 mmol) in THF (1,37 ml) and water (0,67 ml) under ice cooling and the reaction mixture was stirred at room temperature for a period of 14.5 hours. To the reaction mixture was added THF, was then added under ice cooling concentrated sulfuric acid (0.2 ml) and the reaction mixture was stirred for 10 minutes. To the obtained reaction mixture was added saturated aqueous sodium hydrogen carbonate solution and the mixture was stirred at room temperature for 10 minutes. The resulting mixture was extracted with ethyl acetate and the organic layer was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (3:2)] to obtain specified in the header of the product (0.20 g, 100%) as diastereomeric mixture.

1H-NMR (CDCl3) δ: 0,47-0,53 (1H, m), of 0.58 to 0.63(1H, m)of 0.80 to 0.92 (2H, m), 1,09-of 1.27 (2H, m), 1,68-of 1.84 (2H, m), 3,32-of 3.64 (5H, m), 4,34-a 4.53 (4H, m), 4,70-4,88 (5H, m), of 5.84 (0,5H, s), 5,96 (0,5H, s), 6,85-6,97 (3H, m), 7,05-7,35 (21H, m), 7,43-of 7.48 (1H, m,), 8,20-8,24 (2H, m)

MS (ESI+): 762 [M+H]+

(7) Synthesis of 4-[chloro-(4-cyclopropylmethyl)methyl-3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzoyloxymethyl-cyclohexyloxy)pyridine

In a stream of nitrogen thionyl chloride (0.05 ml, of 0.68 mmol) was added to a solution of (4-cyclopropylmethyl)-[3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)pyridine-4-yl]methanol (0.20 g, 0.26 mmol) in methylene chloride (3.0 ml) under ice cooling and the mixture was stirred at room temperature for two hours. To the reaction mixture were added saturated aqueous solution of sodium bicarbonate, the mixture was extracted with methylene chloride and the organic layer was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:1)] to obtain specified in the header of the product (0.20 g, 100%) as diastereomeric mixture.

1H-NMR (CDCl3) δ: 0,51-0,53 (1H, m), and 0.61-of 0.64 (1H, m), 0,83 with 0.93 (2H, m), 1,10-of 1.18 (1H, m), of 1.66-1.77 in (3H, m), 2,15-of 2.27 (1H, m), 3,30-3,66 (5H, m), of 4.38-4,55 (4H, m), a 4.83-4,91 (4H, m), 6,23 (0,5H, s), 6,39 (0,5H, ), 6,85-of 6.96 (3H, m), 7,11-7,33 (21H, m), 7,54-7,58 (1H, m), compared to 8.26-8,42 (2H, m)

MS (ESI+): 780 [M+H]+

(8) Synthesis of 4-(4-cyclopropylmethyl)-3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxybenzyl is xiaxi)pyridine

In a stream of nitrogen to a solution of 4-[chloro-(4-cyclopropylmethyl)-methyl]-3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)pyridine (0,22 g, 0.28 mmol) in methylene chloride (4,1 ml) and acetic acid (12,4 ml) was added zinc (0.14 g, 2.14 mmol) and the resulting mixed solution was stirred at room temperature for 14 hours. To the reaction mixture were added ethyl acetate and the mixture washed with saturated aqueous bicarbonate and dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:1)] to obtain specified in the header of the product (0.14 g, 67%).

1H-NMR (CDCl3) δ: 0,57-of 0.62 (2H, m), 0,86 to 0.92 (2H, m)and 1.51-of 1.59 (1H, m), 1.70 to of 1.85 (2H, m), 2,08-to 2.15 (1H, m), 3,44 (1H, DD, J=9,1, 2,5 Hz), 3,53-3,70 (4H, m), a 3.87 (2H, d, J=1.6 Hz), 4,42-of 4.54 (4H, m), 4,71 (2H, DD, J=17,6, to 10.7 Hz), a 4.83-is 4.93 (3H, m), 6.90 to-7,34 (25H, m), 8,11 (1H, d, J=4,7 Hz), 8,35 (1H, s)

(9) Synthesis of [4-(4-cyclopropylmethyl)pyridine-3-yl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen pentamethylbenzyl (0.40 g, 2,70 mmol) and the solution trichloride boron in methylene chloride (1,0 M, and 1.00 ml, 1.00 mmol) was added to a solution of 4-(4-cyclopropylmethyl)-[3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)pyridine (136 mg, 0.18 mmol) in methylene chloride (7,1 ml) at -78°C and the mixture was stirred at -78°C for 3.5 hours. To the reaction mixture was added methane is l (1.7 ml), then to the mixture was added a solution of sodium methoxide in methanol (1,0 M, 4 ml) and the reaction mixture was stirred at room temperature for 10 minutes. Insoluble substances were filtered off and the filtrate was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (5:1)] to obtain specified in the header of the product (66 mg, 95%).

1H-NMR (CD3OD) δ: 0,60-0,65 (2H, m), from 0.88 to 0.95 (2H, m), 1.06 a-1,19 (1H, m), 1.56 to to 1.61 (1H, m), 1,81-of 1.88 (1H, m), 2.05 is-a 2.12 (1H, m), 3,20-of 3.27 (2H, m), 3,47-3,55 (2H, m), and 3.72 (1H, DD, J=10,7, 3.8 Hz), 3,90-a 4.03 (2H, m), 4,28 is 4.36 (1H, m), 6,97 (2H, TD, J=8,2, 1.9 Hz), 7,07-7,10 (3H, m), of 8.00 (1H, d, J=4,7 Hz), 8,30 (1H, s)

MS (ESI+): 386 [M+H]+

Retention time HPLC: 8,40 minutes

Example 43

[2-(4-Carboxybenzoyl)phenyl]-5a-carb-β-D-glucopyranosid

To a solution in methanol-THF (10 ml-5 ml) of [2-(4-methoxycarbonylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside (72,0 mg, 0.1 mmol)obtained in Example 31 was added to the catalyst 20% palladium hydroxide (7.2 mg). The mixture was stirred in hydrogen atmosphere for 15 hours, then the catalyst was filtered. The solvent drove under reduced pressure to obtain specified in the connection header (38,2 mg, 100%).

1H-NMR (CD3OD) δ: 0,86-1,00 (1H, m)and 1.51 is 1.58 (1H, m), 2,01-2,11 (1H, m), 3,16-to 3.34 (2H, m), 3.43 points-of 3.50 (2H, m), 3,67-to 3.73 (1H, m), 3.95 to 4,88 (3H, m), 6.87 in (1H, t, J=13.5 Hz), 7,03 (1H, d, J=7,4 Hz), 7,12-7,21 (2H, m), 7,30 (2H, d, J=,1 Hz), 7,88 (2H, d, J=8.1 Hz)

MS (ESI+): 389 [M+H]+

Retention time HPLC: 10.6 minutes

Example 44

[2-(4-Vinylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 2-(4-bromobenzyl)phenol

In a stream of nitrogen dimethyldisulfide (1,83 ml of 42.46 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (0.9 ml, 7,07 mmol) was added to a solution of 1-benzyloxy-2-(4-bromobenzyl)benzene (1.0 g, and 2.83 mmol) in methylene chloride (30,0 ml) under cooling with ice. The reaction mixture was stirred for 19 hours while gradually raising its temperature to room temperature, and then to the resulting mixture under ice cooling was added water and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the title compound (527 mg, 70.8 per cent).

1H-NMR (CDCl3) δ: to 3.92 (2H, s), to 4.62 (1H, s), 6.73 x-6,76 (1H, m), 6,85-6,99 (1H, m), 7,06-7,14 (4H, m), 7,35-7,40 (2H, m)

(2) Synthesis of (1S,2R,3S,4R,5R)-trebaseleghe-5-(benzoyloxymethyl)cyclohexylamino ether triftormetilfullerenov acid

Pyridine (205 μl, of 2.53 mmol) was added to a solution of (1S,2R,3S,4R,5R)-Tris-benzyloxy-5-(benzoyloxymethyl)-cyclohexanol (300 mg, 0,557 mmol) in methylene chloride (5.5 m is) and the mixture was cooled to 0°C, then to the mixture was added anhydride triftormetilfullerenov acid (210 μl, 1.25 mmol). The reaction mixture was stirred at the same temperature for one hour, then to the mixture was added saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with methylene chloride. The combined organic layer was washed with a saturated aqueous solution of potassium bisulfate and saturated aqueous sodium chloride and dried over magnesium sulfate. The solvent drove to obtain the crude product (380 mg).

1H-NMR (CDCl3) δ: 1,83 (1H, DD, J=15,9, of 14.0 Hz), 2.00 in and 2.14 (2H, m), 3,39 (1H, DD, J=9,2, 2.3 Hz), 3,50 (1H, DD, J=9,6, and 2.6 Hz), of 3.56 (1H, DD, J=10,2, 9,3 Hz in), 3.75 (1H, DD, J=9,2, 3,4 Hz), 3,86 (1H, DD, J=9,5, and 9.3 Hz), and 4.40 (2H, C)4,50 (1H, d, J=10,8 Hz), to 4.62 (1H, d, J=11,4 Hz), 4,79 (1H, DD, J=10,7 Hz), 4,82 (1H, d, J=11.5 Hz), 4,89 (1H, d, J=10,7 Hz)to 4.92 (1H, d, J=10,7 Hz), 5,33 (1H, usher.), 7,15-7,30 (20H, m)

(3) Synthesis of [2-(4-bromobenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen to a solution of 1-benzyloxy-2-(4-bromobenzyl)benzene (386 mg, of 1.46 mmol) in DMF (1 ml) was cooled in an ice bath, to the mixture was added NaH (60%, 52 mg). The reaction mixture was stirred at the same temperature for 10 minutes, and then this reaction mixture was added dropwise to a suspension of (1S,2R,3S,4R,5R)-trebaseleghe-5-(benzoyloxymethyl)cyclohexylamino ether triftormetilfullerenov acid (655 mg, 0.97 mmol) in DMF (2.5 ml) at -40°C. Rea is operating and the mixture was stirred at the same temperature for two minutes, at temperatures from -40°C to 0°C for 30 minutes and then at 0°C for one hour. To the reaction mixture were added saturated aqueous solution of sodium chloride and water. The resulting solution was extracted with simple ether, the organic layer was washed with water and saturated aqueous sodium chloride and dried over sodium sulfate. The residue obtained by removal of the solvent, subjected to rough purified using column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain the crude product (200 mg). The crude product was dissolved in methylene chloride (2.5 ml) in a stream of nitrogen. To the mixture was added with ice cooling dimethyl sulfide (0.6 ml, 13,48 mmol) and a complex of boron TRIFLUORIDE-diethyl ether (284 μl, 2.2 mmol). The reaction mixture was stirred for 25 hours while gradually raising its temperature to room temperature, and then to the mixture was added water under ice cooling and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the header of the product (40,0 mg, 42.9 per cent).

1H-MR (CD 3OD) δ: 0,85 (1H, square, J=13,2, J=l1,1 Hz), 1,44-to 1.59 (1H, m), 2,03-of 2.09 (1H, m), 3,13 (1H, d, J=8.7 Hz), 3,19 (1H, d, J=5,1 Hz), 3,23-3,26 (2H, m), 3,37 is-3.45 (2H, m), 3,63-3,68 (1H, DD, J=10,6, 3,9 Hz), 3,81 (1H, d, J=14.4 Hz), 4,10 (1H, d, J=14.4 Hz), 4.09 to 4,18 (1H, m), 6,79 (1H, t, J=7.5 Hz), of 6.96 (1H, d, J=9.0 Hz), 7.03 is-7,13 (4H, m), 7,27-to 7.32 (2H, m)

(4) Synthesis of [2-(4-vinylbenzyl)phenyl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen [2-(4-bromobenzyl)phenyl]-5a-carb-β-D-glucopyranoside (40 mg, 0,094 mmol) was dissolved in toluene (2 ml) and the resulting mixture was added tributyltinhydride (36 mg, 0.11 mmol), tetrakis(triphenylphosphine)palladium (0) (2.7 mg) and 2,6-di-tert-butyl-4-METHYLPHENOL and the mixture is boiled under reflux at 110°C for 15 hours. The reaction mixture was cooled to room temperature and the solvent drove away under reduced pressure. The obtained residue was purified using preparative TLC [eluent=methanol:methylene chloride (1:10)] to obtain specified in the header of the product (9 mg, 25.7 per cent).

1H-NMR (CD3OD) δ: 0,86 (1H, square, J=12,0, 11,7), 1,42-1,55 (1H, m), 1,96-2,03 (1H, m), 3,10-3,19 (2H, m), 3,22-of 3.25 (2H, m), 3,36-3,44 (2H, m), 3,63 (1H, DD, J=10,6, 4,1 Hz), 3,81-4,08 (2H, m), 4.09 to to 4.16 (1H, m), 5,07 (1H, DD, J=11,0, 1.2 Hz), 5,63 (1H, DD, J=18,0, 1.2 Hz), is 6.61 (1H, DD, J=18,0, and 11.0 Hz), 6,78 (1H, t, J=7,3 Hz), 7,03 (1H, d, J=6.3 Hz), 7,02-7,24 (6H, m)

MS (ESI+): 370 [M]+

Retention time HPLC: 11.8 minutes

Example 45

{2-[4-(2,2-Defermined)benzyl]phenyl}-5a-carb-β-D-glucopyranosid

(1) Synthesis of 1-diethoxylate-4-(2,2-defermined)benzene

In a stream of nitrogen RA is creative n ' utility in hexane (2,44 M, 9,94 ml) was added dropwise to Diisopropylamine (3,40 ml, and 24.2 mmol), cooled in an ice bath, then to the mixture was added THF (20 ml). The resulting mixture was cooled to -78°C and the resulting mixture was added dropwise diethyl(deformity)phosphonate (3,62 ml of 23.1 mmol). The reaction mixture was stirred at the same temperature for five minutes, then to the mixture was added dropwise terephthalaldehyde monomethylether (4,2 ml, or 21.0 mmol). The reaction mixture was stirred at the same temperature for 50 minutes, at room temperature for 20 minutes and at a temperature of 70-75°C for 34 hours. After cooling the reaction mixture to the reaction mixture were added saturated aqueous solution of ammonium chloride and water and the resulting mixture was extracted with simple ether. The organic layer was washed with a saturated aqueous solution of ammonium chloride and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:20)] to obtain specified in the title compound (1.10 g, 22%).

1H-NMR (CDCl3) δ: 1,24 (6H, t, J=7,1 Hz), 3,45-3,68 (4H, m), 5,27 (1H, DD, J=26,4, and 3.8 Hz), 5,49 (1H, s), 7,32 (2H, d, J=8,4 Hz), 7,44 (2H, d, J=8,4 Hz)

(2) Synthesis of 4-(2,2-defermined)benzaldehyde

In a stream of nitrogen aqueous solution of 2 M hydrochloric acid (2.5 ml) d is balali to a solution of 1-diethoxylate-4-(2,2-defermined)benzene (998,1 mg, of 4.12 mmol) in a simple ether (4 ml), cooled in an ice bath, and the reaction mixture was stirred at the same temperature for three minutes and at room temperature for 3.75 hours. The reaction mixture was extracted with simple ether and the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride and dried over sodium sulfate. The solvent drove under reduced pressure to get crude compound.

1H-NMR (CDCl3) δ: lower than the 5.37 (1H, DD, J=25,7, 3.5 Hz), 7,49 (2H, d, J=8,4 Hz), the 7.85 (2H, d, J=8,4 Hz), 9,98 (1H, s)

(3) Synthesis of (2-benzyloxyphenyl)-[4-(2,2-defermined)phenyl]methanol

In a stream of nitrogen a solution of 2-benzyloxyphenol (1.63 g, 6,18 mmol) in THF (4 ml) was cooled to -78°C and the resulting mixture was added dropwise a solution of n-utility in hexane (2.44 M, 2.66 ml). The reaction mixture was stirred at the same temperature for 25 minutes, then to the mixture was added dropwise a solution previously obtained 4-(2,2-defermined)benzaldehyde in THF (1 ml). The reaction mixture was stirred at the same temperature for 1.25 hours, then to the mixture was added saturated aqueous solution of ammonium chloride and water. The resulting mixture was extracted with simple ether and the organic layer was washed with a saturated aqueous solution of ammonium chloride and dried over sulfate is m sodium. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the connection header (1,17 g, 81%).

1H-NMR (CDCl3) δ: 2,94 (1H, d, J=6,1 Hz), 4,98-5,04 (2H, m), of 5.26 (1H, DD, J=26,4, and 3.8 Hz), 6,03 (1H, d, J=6,1 Hz), 6,88? 7.04 baby mortality (2H, m), 7,14-7,38 (11H, m)

(4) Synthesis of 1-benzyloxy-2-[4-(2,2-defermined)-benzyl]benzene

In a stream of nitrogen to a solution of (2-benzyloxyphenyl)-[4-(2,2-Porvenir)phenyl]methanol (1,14 g, 3,24 mmol) in methylene chloride (10 ml) was cooled to -78°C and the resulting mixture was added triethylsilane (5,17 ml, 32,35 mmol). To the reaction mixture was added dropwise within five minutes the complex of boron TRIFLUORIDE-diethyl ether (0,49 ml, 3.88 mmol) and the reaction mixture was stirred at -78°C for five minutes, and then under ice cooling for 10 minutes. To the mixture was added saturated aqueous sodium hydrogen carbonate solution and water and the resulting solution was extracted with methylene chloride. The organic layer was washed saturated aqueous sodium chloride and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:30)] to obtain specified in the connection header (984,5 mg, 90%).

1H-NMR (CDCl3) δ: 4,00 (2H, s), of 5.05 (2H, s), 5,23 (1H, is d, 3=26,2, and 3.8 Hz), 6,85-to 6.95 (2H, m), 7,05-7,40 (11H, m)

(5) Synthesis of 2-[4-(2,2-defermined)benzyl]phenol

In a stream of nitrogen to a solution of 1-benzyloxy-2-[4-(2,2-defermined)benzyl]benzene (984,5 mg of 2.93 mmol) in methylene chloride (12 ml) was cooled to -78°C and the resulting mixture was added dropwise a solution of tribromide boron-dimethyl sulfide in methylene chloride (1,0 M to 7.32 ml). The reaction mixture was stirred at the same temperature for two minutes and under ice cooling for two hours, then to the mixture was added dropwise a solution of boron TRIFLUORIDE-dimethyl sulfide in methylene chloride (4,39 ml). The reaction mixture was stirred at the same temperature for 3.5 hours, then to the mixture was added aqueous sodium hydroxide solution and saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with methylene chloride, the organic layer was washed saturated aqueous sodium chloride and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:7)] to obtain specified in the connection header (647,5 mg, 90%).

1H-NMR (CDCl3) δ: 3,98 (2H, s), to 4.62 (1H, s), of 5.24 (1H, DD, J=26,2, and 3.8 Hz), 6,78 (1H, d, J=8.1 Hz), 6,84-6,94 (1H, m),? 7.04 baby mortality-to 7.32 (6H, m)

(6) Synthesis of {2-[4-(2,2-defermined)benzyl]phenyl}-5a-carb-β-D-glucopyranoside

In a stream of nitrogen a solution of 2[4-(2,2-defermined)benzyl]phenol (80 mg, 0,324 mmol) in DMF (1 ml) was cooled in an ice bath and the resulting mixture was added NaH (60%, 13 mg). The reaction mixture was stirred at the same temperature for 10 minutes, and then this reaction mixture was added dropwise to a suspension of (1S,2R,3S,4R,5R)-trebaseleghe-5-(benzyloxy-methyl)cyclohexylamino ether triftormetilfullerenov acid (181 mg, 0,270 mmol) in DMF (2.5 ml) at -40°C. the Reaction mixture was stirred at the same temperature for two minutes, at a temperature from -40°C to 0°C for 30 minutes and at 0°C for one hour. To the reaction mixture were added saturated aqueous solution of sodium chloride and water and the mixture was extracted with simple ether, the organic layer was washed with water and saturated aqueous sodium chloride and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:7)] to obtain the target product (180,7 mg). In a stream of nitrogen 65 mg (0,0848 mmol) of this product was mixed with pentamethylbenzene (188 mg, of 1.27 mmol) in a stream of nitrogen and dissolved in methylene chloride (2.5 ml). After cooling the solution obtained mixture to -78°C and the resulting mixture was added dropwise a solution of trichloride boron in methylene chloride (1,0 M of 0.42 ml). The reaction mixture was stirred at the same temperature for 2.25 cha is s, then to the mixture was added dropwise methanol (0.5 ml). At the same temperature was added dropwise a solution of sodium methoxide in methanol (1 M, 1,26 ml) and the reaction mixture was stirred at room temperature for 15 minutes. The mixture was filtered and the filtrate was concentrated under reduced pressure and the obtained residue was purified preparative TLC [eluent=methanol:methylene chloride (1:10)] to obtain specified in the header of the product (to 22.1 mg, 64%).

1H-NMR (CD3OD) δ: 0,82 of-1.04 (1H, m), 1,44-of 1.64 (1H, m), 1,98-2,12 (1H, m), 3,12 of 3.28 (2H, m), 3,40-of 3.54 (2H, m), of 3.69 (1H, DD, J=10,7, 4.0 Hz), with 3.89 (1H, d, J=14,8 Hz), was 4.02 (1H, d, J=14,8 Hz), 4,10-4.26 deaths (1H, m), of 5.40 (1H, DD, J=27,0, 4.0 Hz), 6,78-of 6.90 (1H, m), of 6.96-7,30 (7H, m)

MS (ESI+): 406 [M]+

Retention time HPLC: 18,51 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,h mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4/MeOH (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then in the same conditions [10 mm AcONH4/MeOH (100%)] within five minutes

Flow rate: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Examples 46-58

The target compound was obtained by the same action as described in the above Examples, using appropriate source of prophetic the STV and reagents, respectively.

Example 46

[2-(2,3-Dihydrobenzofuran-5-ylmethyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 0,93 (1H, square, J=13,2 Hz, J=11,4 Hz), 1,49 is 1.58 (1H, m), 2,01-2,07 (1H, dt, J=13,2, and 4.5 Hz), 3,12 (1H, t, J=8,4 Hz), 3,20 (1H, d, J=9,3 Hz)at 3.25 (1H, d, J=4,8 Hz), 3,30-of 3.53 (2H, ra)of 3.69 (1H, DD, J=6,6 and 4.2 Hz), 3,85 (1H, d, J=15 Hz), 3,91 (1H, d, J=15 Hz), 4,13-is 4.21 (1H, m), 4,47 (2H, t, J=8.7 Hz), 6,59 (1H, d, J=8,4 Hz), 6,83 (1H, t, J=7.2 Hz), 6.89 in (1H, d, J=8.1 Hz), 6,99-to 7.15 (4H, m)

MS (ESI+): 386 [M]+

Retention time HPLC: 10.5 minutes

Example 47

[2-(3-Fluoro-4-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 0,99 (1H, square, J=12,6 Hz), 1,48-to 1.59 (1H, m), 2,04-2,10 (1H, dt, J=13,2, 4,2 Hz)to 2.18 (3H, s), 3,18-of 3.32 (2H, m), 3,44-3,51 (2H, m), 3,68 (1H, DD, J=6,9, 3,9 Hz)to 3.89 (1H, d, J=15 Hz), of 3.97 (1H, d, J=15 Hz), 4,14-4,22 (1H, m), for 6.81-of 6.90 (3H, m), 7,00-7,17 (4H, m)

MS (ESI+): 376,4 [M]+

Retention time HPLC: 11.7 minutes

Example 48

[2-(4-Methoxy-3-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 0,94 (1H, square, J=12,9, 11.7 Hz), 1,47-of 1.57 (1H, m), 2,01-2,08 (1H, dt, J=13,2, 4,2 Hz), 2,12 (3H, s), 3,18-to 3.34 (2H, m), 3.45 points-to 3.52 (2H, m), 3,68 (1H, DD, J=6,6, 4,2 Hz in), 3.75 (3H, s), a-3.84 (1H, d, J=14,7 Hz), 3,90 (1H, d, J=14,7 Hz), 4,14-is 4.21 (1H, m), 6,76 (1H, d, J=8.7 Hz), 6,83 (1H, t, J=7.5 Hz), 6,95-to 7.15 (5H, m)

MS (ESI+): 389 [M+H]+

Retention time HPLC: 11.5 minutes

Example 49

[2-(4-(Pyrazole-1-ylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 0,95 (1H, square, J=12,9, and 11.4 Hz), 1,49-to 1.59 (1H, m), 2,02-of 2.09 (1H, dt, J=12,3, 4,2 Hz), 3,20 (1H, d, J=9.0 Hz), 3,23 (1H, d, J=6.3 Hz), 3,4-of 3.53 (2H, m)to 3.67 (1H, DD, J=6,6 and 4.2 Hz), 3,98 (1H, d, J=14,7 Hz), 4,07 (1H, d, J=15 Hz), 4,16-4,24 (1H, m), of 6.49 (1H, s), 6.87 in (1H, t, J=7.5 Hz), 7,05 (1H, d, J=8.1 Hz), 7,14 (2H, d, J=7.5 Hz), 7,35 (2H, d, J=8,4 Hz), 7,56 (2H, d, J=8,4 Hz), 7,68 (1H, s)to 8.12 (1H, s)

MS (ESI+): 411 [M+H]+

Retention time HPLC: 10.5 minutes

Example 50

[2-(3-Chloro-4-methylbenzyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 0,94 (1H, DD, J=24,4, 13,2 Hz), 1,5-of 1.65 (1H, m), is 2.05 (1H, dt, J=13,5, 4,I, Hz), 3,18-to 3.35 (2H, m), 3,43-3,55 (2H, m), 3,70 (1H, DD, J=10,7, 4,1 Hz), 3,82 (3H, s), 3,82 (1H, d, J=14,8 Hz), of 3.97 (1H, d, J=14,8 Hz), 4,15-of 4.25 (1H, m)6,86 (1H, TD, J=7,4, 1.1 Hz), 6,92 (1H, d, J=8,2 Hz), 7,0-7,2 (5H, m)

MS (ESI+): 409 [M+H]+, 431 [M+Na]+

Retention time HPLC: 11.25 minutes

Example 51

[2-(3,4-Methylenedioxybenzyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 1,01 (1H, square, J=a 12.7 Hz), 1,45-of 1.64 (1H, m), 2,04 and 2.13 (1H, m), 3,19-to 3.35 (4H, m), 3.46 in-3,54 (2H, m), 3,69-3,74 (1H, m)to 3.89 (2H, square, J=16.1 Hz), 4,15-4,22 (1H, m), 5,86 (2H, s), of 6.68 (3H, s), 6,85 (1H, t,J=6,1 Hz), 7,00-to 7.18 (3H, m)

MS (ESI+): 389 [M+H]+

Retention time HPLC: 10.6 minutes

Example 52

[2-(4-Cyclobutylmethyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 0,81-to 0.96 (1H, m), 1,45-to 1.61 (1H, m), 1,78-2,37 (7H, m), 3,15-to 3.34 (5H, m), 3,40-3,55 (2H, m), 3,66 was 4.76 (1H, m), of 3.95 (2H, square, J=13,7 Hz), 4,13-4,24 (1H, m), 6.87 in (1H, t, J=8.1 Hz), 6,97-7,17 (7H, m)

MS (ESI+): 425 [M+Na]+

Retention time HPLC: 13.6 minutes

Example 53

[2-(4-Acetylphenyl)phenyl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 084-0,98 (1H, m), 1,50-of 1.56 (1H, m), 2.00 in of 2.08 (1H, m)to 2.55 (3H, s), 3,15-of 3.32 (3H, m), 3,42-3,50 (2H, m), 3,65-3,70 (1H, m), 3,94-4,24 (3H, m), 4,89 (2H, s)6,86 (1H, t, J=7,3 Hz), 7,03 (1H, d, J=8.1 Hz), 7,12-7,20 (2H,, m), 7,34 (2H, d, J=8.1 Hz), 7,86 (2H, d, J=8.1 Hz)

MS (ESI+): 386 [M+1]+

Retention time: 9.8 minutes

Example 54

[2-(4-Methoxybenzyl)-5-were]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 0,92 was 1.06 (1H, m)and 1.51-of 1.66 (1H, m), 2,08 (1H, dt, J=13,2, 4.0 Hz), 2,32 (3H, s), 3,21 is 3.40 (2H, m), 3,47 of 3.56 (2H, m), 3,71-of 3.78 (1H, m), of 3.77 (3H, s), a-3.84 (1H, d, J=14,2 Hz), 3,95 (1H, d, J=14,2 Hz), 4,14-4.26 deaths (1H, m), 6,68-6,72 (1H, m), 6,78-6,85 (2H, m), 6,86-6,91 (1H, m), 6,97 (1H, d, J=7.8 Hz), 7,10-7,16 (2H, m)

MS (ESI+): 388 [M]+

Retention time HPLC: of 11.26 minutes

Example 55

[2-(4-active compounds)thiophene-3-yl]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 1,20 (1H, t, J=7,6 Hz), of 1.40 and 1.80 (1H, m), 2,04-of 2.09 (1H, m), 2,59 (2H, square, J=7,58 Hz), 3,19-3,55 (5H, m), 3,88-of 3.96 (1H, m)to 3.99 (2H, m), 6.89 in (2H, d, J=5.4 Hz), 7,06-to 7.15 (5H, m)

MS (ESI+): 378 [M]+

Retention time HPLC: 11.9 minutes

Example 56

[(Benzothiophen-2-yl)were]-5a-carb-β-D-glucopyranosid

1H-NMR (CD3OD) δ: 1,04 (1H, m), of 1.40 and 1.80 (1H, m), 2,08-of 2.16 (1H, m), 3,14-to 3.67 (5H, m), 4,14 (1H, d, J=15.7 Hz), 4,19-4,27 (1H, m), 4,36 (1H, d, J=15,5 Hz), 6.89 in (1H, DD, J=8,1, and 6.6 Hz), 7,02 (1H, s), 7,07 (1H, d, J=8.1 Hz), 7,17-7,28 (4H, m), 7,63 (1H, d, J=7,6 Hz), 7,71 (1H, d, J=7,6 Hz)

MS (ESI+): 400 [M]+

Retention time HPLC: 12.0 minutes.

Example 57

{2-[1-(4-Cyclopropylmethyl)ethyl]phenyl}-5a-carb-β-D-glucopyranoside [less polar isomer from the military preparative TLC (eluent:methanol:methylene chloride= 1:10)]

1H-NMR (CD3OD) δ: 0,40 (1H, DD, J=9,3, 9.0 Hz), 0.56 to 0,66 (2H, m), 0,84-to 0.96 (2H, m), 1,36-and 1.54 (1H, m), of 1.52 (3H, d, J=6.6 Hz), 1,76-of 1.88 (2H, m), 3.04 from-of 3.12 (1H, DD, J=10,8, 9.9 Hz)at 3.25 (1H, t, J=10,8 Hz), 3,26 is 3.40 (1H, m), 3,42 (1H, t, J=9.9 Hz), to 3.64 (1H, DD, J=10,4, 4,8 Hz), 4,08-4,22 (1H, m), 4,50 (1H, DD, J=12,0, 6.3 Hz), 6,84-6,99 (4H, m), 6,99-7,06 (2H, m), 7,06-7,28 (1H, m), 7,20-7,26 (1H, m)

MS (ESI+): 399 [M+H]+

Retention time HPLC: 12.7 minutes

Example 58

{2-[1-(4-Cyclopropylmethyl)ethyl]phenyl}-5a-carb-β-D-glucopyranoside [more polar isomer, isolated preparative TLC (eluent:methanol:methylene chloride=1:10)]

1H-NMR (CD3OD) δ: 0,56-0,66 (2H, m), 0,84-to 0.96 (2H, m), 1,10 (1H, DD, J=9,6, and 9.0 Hz), 1,44-of 1.64 (1H, m)of 1.53 (3H, d, J=6.6 Hz), 1,76-of 1.88 (1H, m), 2,13 (1H, DDD, J=12,2, 4,5, 3,3 Hz), 3,20 of 3.28 (2H, m), 3,44 (1H, t, J=10,5 Hz), 3,53 (1H, DD, J=11,4, and 6.6 Hz), to 3.73 (1H, DD, J=11,4, 2.4 Hz), 4,06-4,22 (1H, m), 4,50 (1H, DD, J=12,0, 6.3 Hz), 6,82-7,03 (4H, m), 7,06-7,16 (4H, m)

MS (ESI+): 399 [M+H]+

Retention time HPLC: 12.7 minutes

Example 59

[2-(4-Cyclopropylmethyl)-5-methylthiophene-3-yl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of (4-cyclopropylmethyl)-(3-methoxy-5-methylthiophene-2-yl)methanone

Methyliodide (2,53 ml of 40.6 mmol) was added under nitrogen atmosphere to a solution of (4-cyclopropylmethyl)-(3-methoxy-5-thiophene-2-yl)methanone (1,05 g 4,06 mmol)synthesized in the same manner as described in Example 38) in THF (20 ml). This solution was cooled to -78°C and the resulting mixture was added over 20 minutes a solution of diisopropylamide lithium in a mixture of heptane-THF-is TELESOL (2.0 M, 2,44 ml, 4,88 mmol). The reaction mixture was stirred at the same temperature for three hours. To this solution is then added over 20 minutes a solution of diisopropylamide lithium in a mixture of heptane-THF-benzene (2.0 M, 2,44 ml, 4,88 mmol), the reaction mixture was stirred for two hours and the resulting mixture was added a saturated solution of ammonium chloride. The resulting mixture was extracted with ethyl acetate and the organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5)] to obtain specified in the header of the compound (589 mg, 53%).

1H-NMR (CDCl3) δ: 0,74-0,80 (2H, m), 1.00 and was 1.06 (2H, m), 1,91-of 1.97 (1H, m), 2.49 USD (3H, s), 3,81 (3H, s), 6,62 (1H, s), was 7.08 (2H, d, J=7.9 Hz), to 7.68 (2H, d, J=8,3 Hz)

(2) Synthesis of (4-cyclopropylmethyl)-(3-hydroxy-5-methylthiophene-2-yl)methanone

In a stream of nitrogen solution trichloride boron in methylene chloride (1,0 M, 6.4 ml, 6.4 mmol) was added to a solution of (4-cyclopropylmethyl)-(3-methoxy-5-methylthiophene-2-yl)methanone (582 mg, 2.14 mmol) in methylene chloride (12 ml) at -15°C and the reaction mixture was stirred for one hour. To the mixture was added water and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of chloride is the atrium and was dried (anhydrous magnesium sulfate), and then the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=methanol:methylene chloride (1:100)] to obtain specified in the title compound (497 mg, 90%).

1H-NMR (CDCl3) δ: 0.76 to about 0.82 (2H, m), 1,03-1,10 (2H, m), 1.93 and-to 1.98 (1H, m), 2.49 USD (3H, s), to 6.57 (1H, s), to 7.15 (2H, d, J=8,4 Hz), the 7.85 (2H, d, J=8,4 Hz), 12,80 (1H, s)

(3) Synthesis of (4-cyclopropylmethyl)-[5-methyl-3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)thiophene-2-yl]methanone

In a stream of nitrogen diisopropylsalicylic (0,27 ml of 1.39 mmol) was added dropwise to a mixture of (4-cyclopropylmethyl)-(3-hydroxy-5-methylthiophene-2-yl)methanone (360 mg, of 1.39 mmol), (1S,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxypyrrolidine (500 mg, of 0.93 mmol), triphenylphosphine (365 mg, of 1.39 mmol) and toluene (3.1 ml) under cooling with ice. The mixture was stirred at room temperature for 15 hours, then the solvent is kept under reduced pressure and the obtained residue was purified using flash column-chromatography on silica gel [eluent=n-hexane:ethyl acetate (4:1)] to obtain specified in the title compound (237 mg, 33%).

1H-NMR (CDCl3) δ: 0.70 to to 0.73 (2H, m), 0,99-1,02 (2H, m), 1,35 of 1.50 (1H, m), 1,64-1,72 (1H, m), 1,87-of 1.94 (1H, m), 2,07 with 2.14 (1H, m), is 2.44 (3H, s), 3,36 of 3.56 (5H, m), 4,07 is 4.13 (1H, m), 4,33-4,88 (8H, m), is 6.61 (1H, s), 7,01 (2H, d, J=7.9 Hz), 7,05-7,35 (22H, m), a 7.62 (2H, d, J=8,2 Hz)

(4) Synthesis of 2-(4-cyclopropylmethyl)-5-methyl-3-[(1R,2S,3S,4R,5R)-2,3,4-t is essenziale-5-(benzoyloxymethyl)-cyclohexyloxy]thiophene

In a stream of nitrogen chlorotrimethylsilane (and 0.46 ml of 3.56 mmol) and cyanoborohydride sodium (230 mg, 3.65 mmol) was added to a solution of (4-cyclopropylmethyl)-[5-methyl-3-((1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-benzyloxycarbonyloxy)thiophene-2-yl]methanone (237 mg, 0.30 mmol) in acetonitrile (5 ml) under ice cooling and the reaction mixture was stirred at 0°C for one hour. To the mixture was added methylene chloride, and the mixture was subjected to filtration through celite and the solvent of the filtrate is kept under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain specified in the title compound (135 mg, 58%).

1H-NMR (CDCl3) δ: is 0.58-0.65 (2H, m), 0,86-0,94 (2H, m), 1,23 of 1.28 (1H, m), 1,57-of 1.65 (1H, m), 1.77 in is 1.86 (1H, m), 2.06 to a 2.12 (1H, m), of 2.33 (3H, s), 3.43 points-of 3.65 (5H, m), 3,93 (2H, s), 3,98-4,08 (1H, m), of 4.44 (2H, s), 4,51 (1H, d, J=10,8 Hz), 4.75 V-equal to 4.97 (5H, m), 6,55 (1H, s), 6,92 (2H, d, J=8.1 Hz), 7,10 (2H, d, J=8.1 Hz), 7.18 in-7,37 (20H, m)

(5) Synthesis of [2-(4-cyclopropylmethyl)-5-methylthiophene-3-yl]-5a-carb-β-D-glucopyranoside

In a stream of nitrogen pentamethylbenzyl (390 mg, 2,63 mmol) and the solution trichloride boron in methylene chloride (1,0 M to 0.88 ml, 0.88 mmol) was added to a solution of 2-(4-cyclopropylmethyl)-5-methyl-3-[(1R,2S,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)-cyclohexyloxy]thiophene (134 mg, 0.18 mmol) in methylene chloride (6 ml) at -78°C and the reaction mixture was stirred at -78°C for one hour. To reactio the Noah mixture was added methanol and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:ethanol (20:1)] to obtain specified in the title compound (35 mg, 49%).

1H-NMR (CD3OD) δ: of 0.62 and 0.68 (2H, m), from 0.90 to 0.97 (2H, m), 1,10-to 1.21 (1H, m), USD 1.43-of 1.56 (1H, m), 1,82-of 1.95 (1H, m), 2,03-2,11 (1H, m), a 2.36 (3H, s), 3.25 to 3,90 (6H, m), of 3.94 (2H, m), 6,63 (1H, m), 6,98 (2H, d, J=8,4 Hz), 7,11 (2H, d, J=7.9 Hz)

MS (ESI-): 403 [M-N]-

Example 60

[2-(4-active compounds)-5-methylthiophene-3-yl]-5a-carb-β-D-glucopyranosid

The target compound was obtained by the same steps as outlined in Example 59, using appropriate starting compounds and reagents.

1H-NMR (CD3OD) δ: 1,10-1,22 (4H, m), 1,40-and 1.54 (1H, m), 2,02-of 2.09 (1H, m), of 2.33 (3H, s), 2,58 (2H, d, J=7,6 Hz), 3,22-of 3.25 (2H, m), 3,28-to 3.35 (2H, m), 3,39 is-3.45 (1H, m), 3,52 (1H, DD, J=10,7, 6.2 Hz), 3,71 (1H, DD, J=10,7, 4.0 Hz), 3,83-are 3.90 (1H, m), 6,60 (1H, s), 7,06 (2H, d, J=8,2 Hz), 7,11 (2H, d, J=8,2 Hz)

MS (ESI+): 393 [M+H]+, 415 [M+Na]+

Example 61

[5-Chloro-2-(4-cyclopropylmethyl)thiophene-3-yl]-5a-carb-β-D-glucopyranosid

(1) Synthesis of 4-cyclopropyl-N-methoxy-N-methylbenzamide

In a stream of nitrogen a solution of n-utility in hexane (1,6 M, 6.0 ml, 9,59 mmol) was added dropwise to a solution of 1-bromo-4-cyclopropylbenzene (1.8 g, 9,13 mmol) in anhydrous THF (30 ml) at -78° C for 15 minutes. This solution was stirred at -78°C for 10 minutes and to the mixture was added dropwise a solution of N,N'-dimethoxy-N,N'-dimethyloxetane (1,42G, 9,59 mmol) in THF (15 ml). The reaction mixture was stirred at room temperature for 30 minutes. To the reaction mixture were added saturated aqueous solution of ammonium chloride, the mixture was extracted with simple ether and the organic layer was dried over anhydrous magnesium sulfate. After filtering, the solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=n-hexane:ethyl acetate (4:1)] to obtain specified in the header of the compound (875 mg, 95%).

1H-NMR (CDCl3) δ: 0,73-0,78 (2H, m), 0,97-1,03 (2H, m), 1,87-of 1.94 (1H, m)to 3.34 (3H, s), of 3.56 (3H, s), was 7.08 (2H, d, J=8,3 Hz), 7,60 (2H, d, J=8,3 Hz)

(2) Synthesis of (5-chloro-3-methoxythiophene-2-yl)-(4-cyclopropylmethyl)methanone

In a stream of nitrogen a solution of n-utility in n-hexane (1,6 M 2,43 ml, 3.88 mmol) was added dropwise to a solution of 2-bromo-5-chloro-3-methoxythiophene (882 mg, 3.88 mmol), synthesized by the method described in document [L. Org. Chem., 58, 4629-4633 (1993)]in anhydrous THF (15 ml) at -78°C. the mixture was stirred at -78°C for ten minutes and to the mixture was added dropwise a solution of 4-cyclopropyl-N-methoxy-N-methylbenzamide (875 mg, 4.26 deaths mmol) in THF (3 ml). The reaction mixture was stirred at -78°C for 30 minutes. To the reaction mixture were added saturated aqueous solution of ammonium chloride, the resulting mixture was extracted with ethyl acetate and the organic layer was dried over anhydrous Sul is blockhead magnesium. After filtering, the solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=n-hexane:ethyl acetate (4:1)] to obtain specified in the title compound (714 mg, 63%).

1H-NMR (CDCl3) δ: 0.75 to 0,81 (2H, m), 1,02-1,08 (2H, m), 1,92-to 1.98 (1H, m), of 3.80 (3H, s), is 6.78 (1H, s), 7,10 (2H, d, J=8,3 Hz), to 7.68 (2H, d, J=8,3 Hz)

(3) Synthesis of [5-chloro-2-(4-cyclopropylmethyl)thiophene-3-yl]-5a-carb-β-D-glucopyranoside

The target compound was obtained by the same steps as outlined in Example 59, using synthesized (5-chloro-3-methoxythiophene-2-yl)-(4-cyclo-propylphenyl)methanone and related reagents.

1H-NMR (CD3OD) δ: 0,63-0,66 (2H, m), 0.88 to 0,93 (2H, m), 1,15-to 1.21 (1H, m), 1,61-to 1.67 (1H, m), 1,82-to 1.87 (1H, m), 1,99-2,03 (1H, m), 3,22 is 3.57 (4H, m), 3,70-3,74 (1H, m), a 3.87-3,91 (1H, m)to 3.92 (2H, s)6,86 (1H, s), 6,97 (2H, d, J=8.1 Hz), to 7.09 (2H, d, J=8.1 Hz)

MS (ESI+): 425 [M+H]+

Example 62

(1R,2S,3R,6R)-6-[2-(4-cyclopropylmethyl)phenoxy]-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol

(1) Synthesis of 1-(4-cyclopropylmethyl)methyl-2-[(1R,4R,5S,6S)-4,5,6-trebaseleghe-3-(benzoyloxymethyl)cyclohex-2-enyloxy]benzene

In a stream of nitrogen, 2-(4-cyclopropylmethyl)phenol and tributylphosphine (70 μl, 0.28 mmol) was added to a solution of (1S,4R,5S,6S)-4,5,6-Tris(benzyloxy)-3-benzoyloxymethyl)cyclohex-2-enol (51 mg, 0,095 mmol)described in document [J. Org. Chem., 63, 5668-5671 (1998)]in toluene (300 ml) under cooling l the house, then to the mixture was added at the same temperature tetramethyldisiloxane (48 mg, 0.28 mmol). The reaction mixture was stirred at the same temperature for 20 hours, then to the mixture was added hexane, and the precipitate was filtered and the solvent of the filtrate drove away. The obtained residue was purified preparative TLC [eluent=ethyl acetate:n-hexane (1:5) to obtain the specified title compound (44 mg, 62%).

1H-NMR (CDCl3) δ: 0,54 (2H, m), 0,84 (2H, m)of 1.75 (1H, m), 3,82-to 3.92 (3H, m), 3,93 (2H, s), 4,19 (1H, d, J=12,5 Hz), 4,35 (1H, usher.), to 4.41 (1H, d, J=11.7 Hz), 4,46 (1H, d, J=11.8 Hz), br4.61 (1H, d, J=10,7 Hz), and 4.68 (1H, d, J=10,2 Hz), 4.72 in (1H, d, J=10.5 Hz), 4,79 (1H, d, J=10,8 Hz), is 4.85 (1H, d, J=10,7 Hz), 4,99 (1H, d, J=11,0 Hz), 5,04 (1H, user.), the 5.65 (1H, s), 6,8-7,4 (28H, m)

(2) Synthesis of (1R,2S,3R,6R)-6-[2-(4-cyclopropylmethyl)phenoxy]-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol

In a stream of nitrogen to a solution of 1.0 M trichloride boron in methylene chloride (160 μl, 0.16 mmol) was added to a solution of 1-(4-cyclopropylmethyl)methyl-2-[(1R,4R,5S,6S)-4,5,6-Tris-benzyloxy-3-(benzoyloxymethyl)-cyclohex-2-enyloxy]benzene (12 mg, to 0.016 mmol) and pentamethylbenzene (24 mg, 0,17 mmol) in methylene chloride (300 ml) at -78°C and the mixture was stirred at the same temperature for 1.5 hours. After adding methanol, the temperature of the resulting solution was raised to room temperature and the solvent drove away under reduced pressure. The obtained residue was purified preparative TLC eluent=methanol:methylene chloride (1:8)] to obtain specified in the connection header (4,1 mg, 70%).

1H-NMR (CD3OD) δ: 0,61 (2H, m), 0,89 (2H, m)and 1.83 (1H, m), 3,55 (1H, DD, J=10.5V, and 7.8 Hz), and 3.72 (1H, DD, J=10.5V, and 7.8 Hz), with 3.89 (1H, d, J=14,8 Hz), 3,93 (1H, d, J=14,9 Hz), 4,11 (2H, users), is 4.15 (1H, d, J=7.8 Hz), 4,80 (1H, d, J=7,6 Hz), the ceiling of 5.60 (1H, t, J=1.5 Hz), at 6.84 (1H, t, J=7,3 Hz), 6,93 (2H, d, J=8.1 Hz), 7,06 (1H, d, J=8,2 Hz), 6,97-to 7.18 (3H, m)

MS (ESI+): 405 [M+Na]+

Retention time HPLC: 12.5 minutes

Example 63

(1R,2S,3R,6R)-4-Hydroxymethyl-6-[2-(4-methoxybenzyl)-phenoxy]cyclohex-4-ene-1,2,3-triol

(1) Synthesis of 1-(4-methoxyphenyl)methyl-2-[(1R,4R,5S,6S)-4,5,6-trebaseleghe-3-(benzoyloxymethyl)cyclohex-2-enyloxy]benzene

In a stream of nitrogen, 2-(4-methoxybenzyl)phenol (299 mg, of 1.40 mmol) and tributylphosphine (380 μl, 1.53 mmol) was added to a solution of (1S,3S,4S,5R,6R)-4,5,6-trebaseleghe-1-(benzoyloxymethyl)cyclohexane-1,3-diol (561 mg, 1.01 mmol), described in the document [Tetrahedron, 56, 7109-7122 (2000)]in toluene (3 ml) under ice cooling, and then to the mixture was added at the same temperature tetramethyldisiloxane (261 mg, of 1.52 mmol). The reaction mixture was stirred at the same temperature for 20 hours, then to the mixture was added hexane and the precipitate was filtered and the solvent of the filtrate drove away. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:7 → 1:1) to obtain the specified title compound (312 mg, 42%).

1H-NMR (CDCl3) δ: of 3.64 (3H, s), 3,80-of 3.95 (3H, m)to 3.92 (2H, s), 4,19 (1H, d, J=13,6 G is), 4,36 (1H, usher.), to 4.41 (1H, d, J=11,9 Hz), 4,46 (1H, d, J=11.8 Hz), with 4.64 (1H, d, J=11,0 Hz), 4,69 (1H, d, J=10,8 Hz), 4,71 (1H, d, J=10,8 Hz), 4,79 (1H, d, J=10,8 Hz), is 4.85 (1H, d, J=11,0 Hz), 4,99 (1H, d, J=11.0 in Hz)of 5.05 (1H, user.), 5,67 (1H, s)of 6.71 (2H, d, J=8.7 Hz), 6,80-7,40 (26H, m)

MS (ESI+): 755 [M+Na]+

(2) Synthesis of (1R,2S,3R,6R)-4-hydroxymethyl-6-[2-(4-methoxybenzyl)phenoxy]cyclohex-4-ene-1,2,3-triol

In a stream of nitrogen to a solution of 1.0 M trichloride boron in methylene chloride (6.0 ml, 6.0 mmol) was added to a solution of 1-(4-methoxyphenyl)methyl-2-[(1R,4R,5S,6S)-4,5,6-trebaseleghe-3-(benzoyloxymethyl)cyclohex-2-enyloxy]benzene (312 mg, 0,426 mmol) in methylene chloride (12 ml) at -78°C and the mixture was stirred at this temperature for 1.5 hours. After adding methanol, the temperature of the resulting solution was raised to room temperature and the solvent drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=methanol:methylene chloride (1:8)] to obtain specified in the connection header (to 37.9 mg, 24%).

1H-NMR (CD3OD) δ: of 3.56 (1H, DD, J=10,5, 8.0 Hz), to 3.73 (1H, m), of 3.73 (3H, s), 3,88 (1H, d, J=14,9 Hz), 3,92 (1H, d, J=14,9 Hz), 4,11 (2H, users), to 4.16 (1H, m), to 4.81 (1H, m), 5,61 (1H, t, J=1.7 Hz), 6,77 (2H, d, J=8.7 Hz), at 6.84 (1H, t, J=7,3 Hz), of 6.99 (1H, d, J=8.1 Hz),? 7.04 baby mortality (1H, d, J=7.5 Hz), 7,10 (2H, d, J=8,9 Hz), 7,13 (1H, m)

MS (ESI+): 395 [M+Na]+

Retention time HPLC: 10.8 minutes

Example 64

(1R,2S,3S,6R)-4-[3-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol

(1) Synthesis of 3-(-active compounds)phenylboronic acid

In a stream of nitrogen to a solution of 1-bromo-3-(4-active compounds)benzene (2,19 g of 7.96 mmol) in THF (20 ml) was cooled to -78°C, to the mixture was added dropwise a solution of n-utility in hexane (2,44 M 3,42 ml) and the resulting mixed solution was stirred at the same temperature for 20 minutes. After adding trimethylborane (2,68 ml, 23,87 mmol) the reaction mixture was stirred at this temperature for five minutes and at room temperature for 12.5 hours. After cooling the reaction mixture in an ice bath, to the mixture was added dropwise concentrated sulfuric acid (10 ml) and the resulting mixed solution was stirred at the same temperature for one hour. The mixture was extracted with simple ether and the organic layer was washed with water and then dried over sodium sulfate. Hard white substance obtained by distillation of the solvent under reduced pressure, was added hexane-ethyl acetate (10:1) (5 ml), the mixture was filtered, and then the obtained solid was washed with hexane-ethyl acetate (10:1). The obtained white powder was dried under reduced pressure to obtain specified in the connection header (604,2 mg, 32%).

1H-NMR (CDCl3) δ: 1,22 (3H, t, J=7,6 Hz), 2,62 (2H, square, J=7,6 Hz), 4,07 (2H, s), 7,10-7,20 (4H, m), of 7.36-7,44 (2H, m), 8,00-8,10 (2H, m)

(2) Synthesis of (3R,4R,5S,6R)-4,5,6-trebaseleghe-3-(benzoyloxymethyl)cyclohex-1-enrobage EF the RA triftormetilfullerenov acid

In a stream of nitrogen a solution of n-utility in hexane (322 μl, 0,787 mmol) was added dropwise to Diisopropylamine (113 μl, 0,806 mmol), cooled in an ice bath, and to the mixture was added THF (0.8 ml). The resulting solution was cooled to -78°C, was added dropwise a solution of (2R,3S,4R,5R)-2,4,5-trebaseleghe-5-(benzoyloxymethyl)cyclohexanone (205,9 mg, 0.384 mmol) in THF (1 ml) and the mixture was stirred at the same temperature for 12 minutes. To the mixture was added dropwise a solution of N-(5-chloro-2-pyridyl)tripled (452 mg, 1.15 mmol) in THF (1.2 ml) and the reaction mixture was stirred at the same temperature for 2.5 hours. To the mixture was added saturated aqueous sodium hydrogen carbonate solution and water to stop the reaction and the resulting mixture was extracted with simple ether. The organic layer was washed saturated aqueous sodium chloride and dried over sodium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10 → 1:8) to obtain specified in the connection header (161,4 mg, 63%).

1H-NMR (CDCl3) δ: 2,60-2,70 (1H, m), 3,40-to 3.58 (2H, m), 3,70 (1H, DD, J=9,9, 9.7 Hz), 3,90 (1H, DD, J=9,7, 7,1 Hz), 4,32-of 4.54 (4H, m), 4,70-4,94 (5H, m), USD 5.76-of 5.83 (1H, m), 7,10-7,40 (20H, m)

(3) Synthesis of 1-(4-active compounds)-3-[(3R,4R,5S,6S)-4,5,6-trebaseleghe-3-(benzoyloxymethyl)cyclohex-1-enyl]benzene

In the Otok nitrogen dioxane-water (10:l)(12 ml) was added to a mixture of (3R,4R,5S,6R)-4,5,6-trebaseleghe-3-(benzoyloxymethyl)cyclohex-1-enrobage ether triftormetilfullerenov acid (656 mg, 0,981 mmol), K3PO3(250 mg, 1.18 mmol), KBr (140 mg, 1.18 mmol), 3-(4-active compounds)phenylboronic acid (283 mg, 1.18 mmol) and Pd(PPh3)4(56.6 mg, 0,049 mmol) and the reaction mixture was heated and stirred at a temperature of 100-105°C for 26 hours. After cooling the reaction mixture to the mixture was added saturated aqueous solution of sodium chloride and water. The resulting solution was extracted with simple ether and the organic layer was washed saturated aqueous sodium chloride and dried over sodium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10 → 1:8) to obtain specified in the connection header (510,0 mg, 73%).

1H-NMR (CDCl3) δ: 1,19 (3H, t, J=7,6 Hz), 2,58 (2H, square, J=7,6 Hz), 2,64 is 2.75 (1H, m), of 3.54 (1H, DD, J=8,9, 5,9 Hz), to 3.64 (1H, DD, J=8,9, 3.5 Hz), 3,68-with 3.79 (1H, m)to 3.92 (2H, s)4,07 (1H, DD, J=9,7, 7,3 Hz), or 4.31 (1H, d, J=a 10.6 Hz), of 4.45 (2H, s), 4,48 (1H, d, J=a 10.6 Hz), of 4.54 (1H, d, J=10,9 Hz), 4,79-5,00 (4H, m), 5,85-of 5.92 (1H, m), 6.73 x-PC 6.82 (2H, m), 6,98-7,42 (26H, m)

(4) Synthesis of (1R,2S,3S,6R)-4-[3-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol

In a stream of nitrogen to a solution of 1-(4-active compounds-3-[(3R,4R,5S,6S)-4,5,6-trebaseleghe-3-(benzoyloxymethyl)cyclohex-2-enyloxy]benzene (494.5 mg, 0,692 mmol) and pentamethylbenzene (1,05 g, 7,06 mmol) in methylene chloride (38 ml) was cooled to -78°C and the resulting mixture was added dropwise a solution of Bl 3in methylene chloride (1,0 M, 7,54 ml). The reaction mixture was stirred at this temperature for ten minutes and at -70°C for 1.5 hours, then to the mixture was added methanol (20 ml). The residue obtained by removal of the solvent under reduced pressure, subjected to rough purified using a column of chromatography on silica gel [eluent=methanol:methylene chloride(1:20 →1:10), and then was purified preparative TLC [eluent=methanol:methylene chloride (1:10)] to obtain specified in the connection header (46.2 mg, 19%).

1H-NMR (CD3OD) δ: 1,19 (3H, t, J=7,6 Hz), 2,27 is 2.44 (1H, m), 2,58 (2H, square, J=7,6 Hz), 3,44-3,68 (3H, m), 3,76-of 3.94 (3H, m), 4,45-of 4.57 (1H, m), 5,74 of 5.84 (1H, m), 6,95-of 7.25 (8H, m)

MS (ESI+): 372 [M+H2O]+

Retention time HPLC: 18,37 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,0x150 mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4/MeOH (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then in the same conditions [10 mm AcONH4/MeOH (100%)] within five minutes

Flow rate: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Example 65

(1R,2R,3S,4R,5R)-1-[3-(4-active compounds)-4-methoxyphenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

(1) Synthesis of (1R,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)-1-[3-4-active compounds)-4-methoxyphenyl]cyclohexanol and (1S,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)-1-[3-(4-active compounds)-4-methoxyphenyl]cyclohexanol

In a stream of nitrogen a solution of n-utility in hexane (2,70 M, of 1.03 ml) was added dropwise to a solution of 4-bromo-2-(4-active compounds)-1-methoxybenzene (908 mg, 2,98 mmol) in THF (10 ml) and cooled to -78°C. the Reaction mixture was stirred at the same temperature for 10 minutes. To this solution was added dropwise a solution of (2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)cyclohexanone (1,00 g of 1.86 mmol) in THF (2 ml) and the resulting solution was stirred at -78°C for 30 minutes. The reaction was stopped by adding a saturated aqueous solution of ammonium chloride and water. The resulting solution was extracted with ethyl acetate and the organic layer was washed with water and then dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:5 → 1:1) to give (1R,2R,3S,4R,5R)-2,3,4-Tris-benzyloxy-5-(benzoyloxymethyl)-1-[3-(4-active compounds)-4-methoxyphenyl]cyclohexanol (0.32 g, 23%) and (1S,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)-1-[3-(4-active compounds)-4-methoxyphenyl]cyclohexanol (0,89 g, 64%).

(1R)-isomer:1H-NMR (CDCl3) δ: 1,17 (3H, t, J=7,6 Hz), 1,80-2,00 (2H, m), 2,20-of 2.36 (1H, m)to 2.55 (2H, d, J=7,6 Hz), 2.91 in (1H, d, J=2.0 Hz), 3,35-of 3.42 (1H, m), 3,65-4,05 (10H, m), to 4.41 is 4.45 (3H, m), 4,59 (1H, d, J=10,7 Hz), to 4.81 (1H, d, J=10,7 Hz), to 4.87 (1H, d, J=10,7 Hz), the 4.90 (1H, d, J=10,7 Hz), 6,78-6,84 (3H, m), 6,99-7,20 (6H, m), 7,20-7,40 (18H, m)

(1S)-isomer:1H-NMR (CDCl3) δ: 1,12(3H, t, J=7,6 Hz), 1,40-and 1.54 (2H, m), 1,78-of 1.88 (1H, m), 2,35 (1H, DD, J=3.3, which is 13.7 Hz), 2,43 (1H, s), 2,47 (2H, square, J=7,6 Hz)to 3.34 (1H, DD, J=0,9, a 8.9 Hz), 3,53-and 3.72 (4H, m), of 3.80 (3H, s), 3,86-3,93 (2H, m)to 4.41 (2H, s), 4,49 (1H, d, J=10,7 Hz), 4,67-rate 4.79 (2H, m), a 4.83 (1H, d, J=10,7 Hz), 5,02 (1H, d, J=11.7 Hz), 6,78 (1H, d, J=8,4 Hz), 7,00 (2H, d, J=7.9 Hz), 7,10 (2H, d, J=7.9 Hz), 7,14-7,20 (2H, m), 7,21-7,40 (18H, m), 7,56-7,63 (2H, m)

(2) Synthesis of (1R,2R,3S,4R,5R)-1-[3-(4-active compounds)-4-methoxyphenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

To a solution of (1R,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)-1-[3-(4-active compounds)-4-methoxyphenyl]cyclohexanol (50.0 mg, 0,067 mmol) in THF (0.5 ml) and methanol (2 ml) was added catalyst a 20% palladium hydroxide (10 mg) and the mixture was stirred in hydrogen atmosphere at room temperature for 15 hours. After the catalyst was filtered, the filtrate was concentrated under reduced pressure. The obtained residue was purified preparative TLC [eluent=methanol:methylene chloride (1:10)] to obtain specified in the title compound (20 mg, 74%).

1H-NMR (CD3OD) δ: 1,22 (3H, t, J=7,6 Hz), 1,65-of 1.84 (2H, m), 2,01 with 2.14 (1H, m)2,60 (2H, square, J=7,6 Hz), 3,39-of 3.46 (1H, m), 3,62 of 3.75 (4H, m), 3,82 (3H, s), of 3.94 (2H, s)6,94 (1H, d, J=8,4 Hz), 7,06 (2H, d, J=8,2 Hz), 7,13 (2H, d, J=8,2 Hz), 7,30-7,38 (2H, m)

MS (ESI+): 420 [M+H2On]+

Retention time HPLC: 17,70 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,0x150 mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4 /MeOH (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then in the same conditions [10 mm AcONH4/MeOH (100%)] within five minutes

Flow rate: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Example 66

(1R,2R,3S,4S,6R)-4-[3-(4-active compounds)-4-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

(1) Synthesis of 2-(4-active compounds)-1-methoxy-4-[(1S,2S,3R,4R,5R)-2,3,4-trebaseleghe-5-(benzyloxyethyl)cyclohexyl]benzene

A solution of (1S,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)-1-[3-(4-active compounds)-4-methoxyphenyl]-cyclohexanol (124 mg, 0.16 mmol)obtained in Example 65, in methylene chloride (2 ml) was cooled to -5°C and the resulting mixture was added triethylsilane (0,39 ml of 2.44 mmol). To the mixture was added traitorously acid (to 0.12 ml, 1.6 mmol) and the reaction mixture was stirred at -5°C for one hour, then to the mixture was added a saturated solution of sodium bicarbonate. The resulting mixture was extracted with methylene chloride and the organic layer was washed saturated aqueous sodium chloride and then dried over sodium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:9)] to obtain specified in the title compound (10 mg, 8%).

1H-NMR (CDCl ) δ: 1,17 (3H, t, J=7,6 Hz), 1,58 is 1.96 (3H, m), of 2.56 (2H, square, J=7,6 Hz), 2,55-2,70 (1H, m), 3,43-3,62 (5H, m), 3,78-4,00 (6H, m), 4,43 (2H, s), of 4.44 (1H, d, J=9.9 Hz), 4,56 (1H, d, J=10,8 Hz), 4,82-is 4.93 (3H, m), 6,75-PC 6.82 (3H, m), 6,99-to 7.18 (9H, m), 7,20-7,38 (15H, m)

(2) Synthesis of (1R,2R,3S,4S,6R)-4-[3-(4-active compounds)-4-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

To a solution of 2-(4-active compounds)-1-methoxy-4-[(lS,2S,3R,4R,5R)-2,3,4-Tris-benzyloxy-5-(benzyloxyethyl)cyclohexyl]benzene (10 mg, of 0.013 mmol) in THF (0.2 ml) and methanol (1 ml) was added catalyst a 20% palladium hydroxide (10 mg) and the mixture was stirred in hydrogen atmosphere at room temperature for 13 hours. After the catalyst was filtered, the filtrate was concentrated under reduced pressure. The obtained residue was purified preparative TLC [eluent=methanol:methylene chloride (1:10)] to obtain specified in the title compound (3.9 mg, 75%).

1H-NMR (CD3OD) δ: of 1.23 (3H, t, J=7.4 Hz), of 1.34 to 1.48 (1H, m), 1,60 to 1.76 (1H, m)and 1.83 (1H, dt, J=13,5, 3.5 Hz), 2,48-of 2.66 (3H, m), 3,30-to 3.38 (2H, m), 3,42-to 3.52 (1H, m), to 3.58-the 3.65 (1H, m), of 3.77 (1H, d, J=4.0 Hz), 3,82 (3H, C)to 3.92 (2H, s)6,91 (1H, d, J=8,2 Hz), 7,02-7,14 (6H, m)

MS (ESI+): 406 [M+H2On]+

Retention time HPLC: 12,53 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,0x150 mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4/MeOH (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then in the same conditions [10 mm AcONH4/Meon (100%)] is within five minutes

Flow rate: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Example 67

(1R,2R,3S,4R,5R)-1-[2-Ethyl-5-(4-active compounds)phenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

(1) Synthesis of (3-bromo-4-ethoxyphenyl)-(4-ethylphenyl)methanol

THF (10 ml) was added to magnesium (353 mg, 14.5 mmol), and then to the mixture was added dropwise 1-bromo-4-ethylbenzene (2 ml, 14.5 mmol) and the mixture was heated to boiling point under reflux for one hour. The reaction mixture was cooled to 0°C, the mixture was added a solution of 3-bromo-4-ethoxybenzaldehyde (2,21 g, 9,68 mmol) in THF (5 ml) and the reaction mixture was stirred at the same temperature for 1.5 hours. To the reaction mixture were added saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=n-hexane → n-hexane:ethyl acetate (3:1)] to obtain specified in the title compound (2.83 g, 88%).

1H-NMR (CDCl3) δ: 1,22 (3H, t, J=7,6 Hz)of 1.45 (3H, t, J=7,0 Hz), and 2.14 (1H, d, J=3.5 Hz), 2,63 (2H, square, J=7.5 Hz), 4,07 (2H, square, J=7,0 Hz), 5,74 (1H, d, J=3.5 Hz), 6,83 (1H, d, J=8,4 Hz), 7,17 (2H, d, J=8,1 is C), 7,20-7,30 (3H, m), 7,56 (1H, d, J=2.1 Hz)

(2) Synthesis of 2-bromo-1-ethoxy-4-(4-active compounds)benzene

Triethylsilane (2,7 ml and 16.9 mmol) and the complex of boron TRIFLUORIDE-diethyl ether (1.2 ml, 9.47 mmol) was added to a solution of (3-bromo-4-ethoxyphenyl)-(4-ethylphenyl)methanol (2.83 g, 8,44 mmol) in methylene chloride (20 ml) at 0°C and the mixture was stirred for three hours. To the reaction mixture were added methanol (50%)-water (4 ml) and the resulting mixture was extracted with methylene chloride. The extract was washed with a saturated aqueous solution of sodium chloride and then dried over magnesium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel {eluent=n-hexane → n-hexane-ethyl acetate [4%(vol./about.)]} obtaining specified in the connection header (2,69 g, 100%).

1H-NMR (CDCl3) δ: 1,22 (3H, t, J=7,6 Hz)of 1.45 (3H, t, J=7.0 Hz), 2,62 (2H, square, J=7,6 Hz), 3,85 (2H, s)4,06 (2H, square, J=7,0 Hz), 6,79 (1H, d, J=8,4 Hz), 7,00-to 7.15 (3H, m), of 7.36 (1H, d, J=2.1 Hz)

(3) Synthesis of (1R,2R,3S,4R,5R)- and (1S,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[2-ethoxy-5-(4-active compounds)phenyl]cyclohexanol

In a stream of nitrogen a solution of n-utility in hexane (1.59 M, 2.30 ml, 3,66 mmol) was added dropwise to a solution of 2-bromo-1-ethoxy-4-(4-active compounds)benzene (1.18 g, 3,70 mmol) in THF (9 ml) and cooled to -78°C. the Reaction mixture was stirred at the same temperature for one hour, then to the mixture was added p the drop wise addition of a solution of (2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)cyclohexanone (1,50 g, 2,80 mmol) in THF (4.5 ml) and the reaction mixture was stirred at -78°C for 10 minutes. To the mixture was added saturated aqueous solution of ammonium chloride to stop the reaction. The resulting mixture was extracted with ethyl acetate, the organic layer was washed saturated aqueous sodium chloride and then dried over magnesium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain (1R)-isomer (884 mg, 41%) and (1S)-isomer (740 mg, 34 %).

(1R)-isomer:1H-NMR (CDCl3) δ: of 1.23 (3H, t, J=7,6 Hz)to 1.37 (3H, t, J=7.0 Hz), 1,70 (1H, DD, J=14,3, 4,1 Hz), of 2.20 to 2.35 (1H, m), 2,62 (2H, square, J=7,6 Hz), 2,67-2,82 (1H, m), 3,0-3,3 (1H, usher.), of 3.43 (1H, DD, J=8,8, 2,O Hz), 3,71 (1H, DD, J=9,8, or 9.8 Hz), 3,83 (1H, DD, J=8,9, 4,O Hz), 3,86-4,10 (3H, m), 3,91 (2H, s), of 4.44 (2H, s), 4,48 (1H, d, J=10.3 Hz), 4,58 (1H, usher.), 4,63 (1H, d, J=10.3 Hz), is 4.85 (1H, d, J=11,0 Hz), 4,88 (1H, d, J=11.0 in Hz)of 4.95 (1H, d, J=10,8 Hz), to 6.75 (1H, d, J=8,4 Hz), 6,79 (2H, d, J=7,0 Hz), 7,00-7,40 (24H, m), 7,53 (1H, d, J=2.0 Hz)

(1S)-isomer:1H-NMR (CDCl3) δ: of 1.12 (3H, t, J=7,6 Hz)of 1.30 (3H, t, J=7.2 Hz), 1,40-of 1.55 (1H, m)of 1.76 (1H, DD, J=13.3-inch and 13.3 Hz), 2,50 (2H, square, J=7,6 Hz), is 2.74 (1H, DD, J=13,7, a 3.2 Hz), to 3.38 (1H, DD, J=9,0, 2,8 Hz), of 3.54 (1H, DD, J=9,0, at 5.3 Hz), to 3.64 (1H, DD, J=10,8, and 8.7 Hz), 3,86 (1H, DD, J=a 9.5, 9.5 Hz), with 3.89 (2H, s), 4,0-4,1 (2H, m), 4,39 (2H, s), a 4.53 (1H, DD, J=11.0 cm Hz), with 4.64-4.72 in (3H, m), of 4.77 (1H, d, J=11.7 Hz), 4,79 (1H, d, J=10.5 Hz), to 4.87 (1H, d, J=10,8 Hz), to 4.98 (1H, d, J=11.7 Hz), 6,98-7,42 (25H, m), to 7.67 (1H, d, J=1,8 Hz)

(4) Synthesis of (1R,2R,3S,4R,5R)-1-[2-ethoxy-5-(4-active compounds)FeNi is]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

To a solution of (1R,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)-1-[2-ethoxy-5-(4-active compounds)phenyl]-cyclohexanol (600 mg, 0,772 mmol) in THF (6 ml) and methanol (3 ml) was added catalyst a 20% palladium hydroxide (60 mg) and the mixture was stirred in hydrogen atmosphere for 2.5 hours. After the catalyst was filtered, the filtrate was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel {eluent=methylene → methylene chloride methanol [12%(vol./about.)]} obtaining specified in the title compound (197 mg, 61%).

1H-NMR (CD3OD) δ: of 1.18 (3H, t, J=7,6 Hz), USD 1.43 (3H, t, J=7.0 Hz), 1,60 (1H, DD, J=14,3, 4,1 Hz), a 2.01 (1H, m), 2,43 (1H, DD, J-14,0, 13,0 Hz), to 2.57 (2H, square, J=7.5 Hz), 3,39 (1H, DD, J=10,5, and 9.3 Hz), 3,60-3,68 (3H, m), 3,85 (2H, s), a 4.03 (2H, m), 4,34 (1H, d, J=9,2 Hz), PC 6.82 (1H, d, J=8,2 Hz), of 6.99 (1H, DD, J=8,4 Hz, 2.3 Hz), was 7.45 (1H, d, J=2.3 Hz)

MS (ESI+): 434 [M+H2O]+

Retention time HPLC: 18,71 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,0x150 mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4/Meon (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then in the same conditions [10 mm AcONH4/MeOH (100%)] within five minutes

Flow rate: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Example 68

(1R,2R3S,4S,6R)-4-[2-Ethoxy-5-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

(1) Synthesis of (1R,2R,3S,4S,6R)-4-[2-ethoxy-5-(4-

the active compounds)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

To a solution in THF (4 ml) and methanol (2 ml) of (1S,2R,3S,4R,5R)-2,3,4-Tris-benzyloxy-5-benzoyloxymethyl-1-[2-ethoxy-5-(4-active compounds)phenyl]cyclohexanol (402 mg, 0,517 mmol)obtained in Example 67, was added the catalyst of 20% palladium hydroxide (78 mg) and the resulting mixed solution was stirred in an atmosphere of hydrogen for 19 hours. After the catalyst was filtered, the filtrate was concentrated under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (10:1)] to obtain specified in the title compound (42 mg, 20%).

1H-NMR (CD3OD) δ: of 1.18 (3H, t, J=7,6 Hz), 1,25-1,50 (1H, m)to 1.38 (3H, t, J=7.0 Hz), of 1.62 (1H, m), of 1.78 (1H, m), 2.57 m (2H, square, J=7,6 Hz), 2.95 and is 3.15 (1H, usher.), 3,25-to 3.33 (2H, m), of 3.54 (1H, DD, J=10,8, 6,1 Hz), to 3.73 (1H, DD, J=10,8, and 3.8 Hz), 3,65-of 3.85 (1H, m), 3,83 (2H, s), of 4.00 (2H, square, J=7,0 Hz), for 6.81 (1H, d, J=8,4 Hz)6,94 (1H, DD, J=8,3, 2,1 Hz),? 7.04 baby mortality (1H, d, J=1,7 Hz), 7,06 (4H, s)

MS (ESI+): 401 [M]+

Retention time HPLC: 12,98 minutes

Examples 69-74

The target compound was obtained by the same action as described in Example 67 or Example 68, using appropriate starting compounds and the reactants, respectively.

Example 69

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2,4-acid]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

sup> 1H-NMR (CD3OD) δ: 1,17 (3H, t, J=7,6 Hz)to 1.61 (1H, DD, J=13,9, and 3.8 Hz), 1,90-2,10 (1H, m), 2,22 (1H, DD, J=13,9, 13,2 Hz)to 2.55 (2H, square, J=7,6 Hz), 3,32-of 3.42 (1H, m), to 3.58-3,70 (3H, m), 3,76-3,88 (2H, m), of 3.80 (3H, s), 3,84 (3H, s), 4,19 (1H, d, J=9.1 Hz), to 6.58 (1H, s)to 7.00 (2H, d, J=8,2 Hz), 7,06 (2H, d, J=8,2 Hz), 7,35 (1H, s)

MS (ESI+): 455 [M+Na]+

Retention time HPLC: 17,83 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,0x150 mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4/MeOH (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then in the same conditions [10 mm AcONH4/MeOH (100%)] within five minutes

Flow rate: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Example 70

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2,4-acid]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

1H-NMR (CD3OD) δ: 1,17 (3H, t, J=7,6 Hz), 1,24 is 1.48 (1H, m), 1,52-to 1.82 (2H, m), of 2.56 (2H, d, J=7,6 Hz), 2,86-is 3.08 (1H, m), 3,24-3,29 (1H, m), 3,48-to 3.67 (2H, m), 3,68-a-3.84 (3H, m), with 3.79 (3H, s), 3,81 (3H, s), 6,56 (1H, C)6,93 (1H, s), 7,01 (2H, d, J=8.6 Hz), 7,05 (2H, d, J=8.6 Hz)

MS (ESI+): 416 [M]+

Retention time HPLC: 18,26 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,0x150 mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4/MeOH (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then those who e conditions [10 mm AcONH 4/MeOH (100%)] within five minutes

Flow rate: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Example 71

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-were]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

1H-NMR (CD3OD) δ: 1,19 (3H, t, J=7,6 Hz)to 1.70 (1H, m), of 1.94 (1H, m), is 2.05 (1H, m), of 2.53 (3H, s), 2,58 (2H, square, J=7,6 Hz), 3,40 (1H, d, J=9,2 Hz), to 3.67 (2H, d, J=4.6 Hz), to 3.73 (1H, d, J=9,2 Hz), a 3.87 (2H, s), 4,01 (1H, d, J=9,2 Hz), 6,91 (1H, DD, J=7,6, 1,S Hz), 7,01 (1H, d, J=7,6 Hz), 7,07 (4H, m), 7,42 (1H, s)

MS (ESI+): 409 [M+Na]+

Example 72

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-were]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

1H-NMR (CD3OD) δ: 1,19 (3H, t, J=7,6 Hz), of 1.24 to 1.37 (1H, m), 1,59-of 1.81 (2H, m), is 2.30 (3H, s), to 2.57 (2H, square, J=7,6 Hz), with 2.93 (1H, m)to 3.34 (2H, m), 3,50-3,63 (2H, m in), 3.75 (1H, DD, J=10,7, 4,2 Hz), 3,86 (2H, s), 6.87 in (1H, d, J=7,6 Hz), 7,03 (1H, d, J=7,6 Hz, 2.1 Hz), 7,07 (4H, s), 7,11 (1H, s)

MS (ESI-): 369 [M-H]-

Example 73

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-methoxyphenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

1H-NMR (CD3OD) δ: of 1.13 (3H, t, J=7,6 Hz), and 1.56 (1H, DD, J=14,1, 3,9 Hz), 1,94-2,04 (1H, m), 2,24 (1H, DD, J=13,9, 13,2 Hz), of 2.51 (2H, square, J=7.5 Hz), 3,24-3,37 (1H, m), 3,57-3,63 (3H, m), 3,74 (3H, s), 3,80-are 3.90 (2H, m), 4,22 (1H, d, J=9.1 Hz), to 6.80 (1H, d, J=8,4 Hz), 6,95-7,01 (5H, m), 7,41 (1H, d, J=1.2 Hz)

MS (ESI+): 425 [M+Na]+

Retention time HPLC: 11.69 minutes

Example 74

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-methoxyphenyl]-6-(hydroxymethyl)the CEC shall Alexan-1,2,3-triol

1H-NMR (CD3OD) δ: of 1.18 (3H, t, J=7,6 Hz), 1,24 of 1.50 (1H, m), 1,54-of 1.85 (2H, m), 2.57 m (2H, d, J=7,6 Hz), 2,90-3,18 (1H, m), 3,24-to 3.34 (2H, m), of 3.54 (1H, DD, J=10,7, 5,9 Hz), 3,60-of 3.78 (2H, m), 3,76 (3H, s), 3,83 (2H, s), PC 6.82 (1H, d, J=8,4 Hz), of 6.96 (1H, DD, J=8,4, 2.0 Hz), 7,01-7,11 (5H, m)

MS (ESI+): 404 [M+H2O]+

Retention time HPLC: of 12.33 minutes

Example 75

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-trifloromethyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

The target compound was obtained by the same action as described in Example 67, using appropriate starting compounds and reagents.

1H-NMR (CD3OD) δ: 1,17 (3H, t, J=7,6 Hz), 1,73 (1H, d, J=10.1 Hz), 2.00 in a 2.12 (2H, m), 2,58 (2H, square, J=7.5 Hz), the 3.35 (1H, DD, J=9,3, and 9.3 Hz), to 3.58-and 3.72 (2H, m), 3,66 (1H, DD, J=9,2, 9,2 Hz), 3,93 (2H, s)to 3.99 (1H, d, J=a 8.9 Hz), to 7.09 (4H, s), 7,13 (2H, m), of 7.69 (1H, d, J=1.4 Hz)

MS (ESI+): 474 [M+Na]+

Retention time HPLC: to 13.09 minutes

Examples 76-78

The target compound was obtained by the same action as described in Example 68, using appropriate starting compounds and the reactants, respectively.

Example 76

(1R,2R,3S,4S,6R)-4-[5-(4-Isopropylbenzyl)-2-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

1H-NMR (CD3OD) δ: 1,21 (6H, d, J=6.9 Hz), 1,29-of 1.42 (1H, m), 1,59-of 1.81 (2H, m), 2,78-2,89 (1H, m), 3,06-3,10 (1H, m), 3,26-to 3.34 (2H, m), 3,55 (1H, DD, J=10,7, 6,0 Hz), 3,62-of 3.85 (5H, m), a-3.84 (2H, s), PC 6.82 (1H, d, J=8,5 Hz), of 6.96 (1H, DD, J=8,2, 2.2 Hz), 7,05-7,11 (5H, m)

MS (ESI+): 400 [M]+

Retention time HPLC: 13,07 minutes

Example 77

(1R,2R,3S,4S,6R)-4-[3-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

1H-NMR (CD3OD) δ: 1,24 (3H, t, J=7.5 Hz), 1,43-of 1.53 (1H, m), 1,61-of 1.78 (1H, m), of 1.85 (1H, dt, J=13,4, and 3.7 Hz), 2,56 of 2.68 (3H, m), 3,29 is 3.40 (2H, m), 3,50-3,66 (2H, m), 3,80 (1H, DD, J=10,9, 3,9 Hz), of 3.94 (2H, s),? 7.04 baby mortality-7,27 (8H, m)

MS (ESI+): 357 [M]+

Retention time HPLC: 12,12 minutes

Example 78

(1R,2R,3S,4S,6R)-4-[3-(4-Hydroxybenzyl)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

1H-NMR (CD3OD) δ: 1,43-of 1.52 (1H, m), 1,64-of 1.78 (1H, m), of 1.85 (1H, dt, J=12,5, and 3.7 Hz), 2,55-of 2.66 (1H, m), 3.33 and is 3.40 (2H, m), 3,50-of 3.64 (2H, m), 3,76-a-3.84 (1H, m), 3,88 (2H, s), 6,68-6,74 (2H, m), 7,00-7,14 (5H, m), 7,20-7,25 (1H, m)

MS (ESI+): 362 [M+H2O]+

Retention time HPLC: 13,70 minutes

Example 79

(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-hydroxyphenyl-6-(hydroxymethyl)cyclohexane-1,2,3-triol

In a stream of nitrogen to a solution of (1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol (40 mg, 0.1 mmol)obtained in Example 74, in methylene chloride (1 ml) was cooled to -78° and to the mixture was added dropwise a solution of BBr3in methylene chloride (1,0 M, 0,31 ml) and the mixture was stirred at the same temperature for 10 minutes and cooled with ice for two hours. Then to the mixture was again added dropwise a solution of BBr3in methylene chloride (0.2 ml) and the resulting mixed solution was stirred under a decree which authorized the temperature for 3.5 hours, and then was added a solution of sodium hydroxide in methanol (0,93 ml). The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain wannago the title compound (3.5 mg, 9.1 per cent).

1H-NMR (CD3OD) δ: 0,87-0,98 (1H, s)to 1.19 (3H, t, J=7.8 Hz), 1,39-of 1.52 (1H, m), 1,59-of 1.66 (1H, m), 1,78 of-1.83 (1H, dt, J=13,5, 3.6 Hz), of 2.56 (2H, square, J=7,8, 7.5 Hz), 2,96-of 3.07 (1H, m), 3,34 (1H, s), 3,54-3,59 (1H, m), 3,62-of 3.69 (1H, m), and 3.72 (1H, DD, J=6,6, 3,9 Hz), 3,80 (2H, s), of 6.68 (1H, d, J=8,4 Hz), to 6.80 (1H, DD, J=8,4, 2.0 Hz), of 6.99 (1H, s), 7,05 (4H, s)

MS (ESI+): 372 [M]+

Retention time HPLC: 11.2 minutes

Example 80

(1R,2R,3S,4S,6R)-4-[3-(4-Cyclopropylmethyl)phenyl-6-(hydroxymethyl)cyclohexane-1,2,3-triol

(1) Synthesis of 4-[3-((3aS,4S,5aR,9aR,9bR)-2,2,8,8-tetramethyl-hexahydro[1,3]dioxolo[4',5':3,4]benzo-[1,2-d][1,3]dioxin-4-yl)benzyl]phenol

(1R,2R,3S,4S,6R)-4-[3-(4-Hydroxybenzyl)phenyl-6-(hydroxymethyl)cyclohexane-1,2,3-triol (47 mg, 0,136 mmol)obtained in Example 78 was dissolved in N,N-dimethylformamide (1 ml) and the resulting mixture was stirred under ice cooling. To the reaction mixture was added 2,2-dimethoxypropane (142 mg, of 1.36 mmol), and then hydrate p-toluensulfonate acid (2 mg). The resulting mixture was stirred at room temperature for 30 minutes and was added saturated aqueous solution of ammonium chloride to stop the reaction. The mixture was extracted with ethyl acetate and organizes the second layer was washed with water and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified preparative TLC [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (34 mg, 59%).

1H-NMR (CDCl3) δ: 1,11-1,24 (1H, m)of 1.42 (6H, s)of 1.46 (3H, s)of 1.53 (3H, s)of 1.73 (1H, dt, J=13,7, 3,9 Hz), 1,80-of 1.93 (1H, m)to 2.94 (1H, dt, J=4.0 a, and 11.0 Hz), 3,59-3,92 (7H, m), is 4.85 (1H, s)of 6.71-6,76 (2H, m), 7,00-was 7.08 (5H, m), 7,19-of 7.23 (1H, m)

(2) Synthesis of 4-[3-((3aS,4S,5aR,9aR,9bR)-2,2,8,8-tetramethyl-hexahydro-[1,3]dioxolo[4',5':3,4]benzo[1,2-d][l,3]dioxin-4-yl)benzyl]phenyl ester triftormetilfullerenov acid

4-[3-((3aS,4S,5aR,9aR,9bR)-2,2,8,8-Tetramethylhexadecane-[1,3]dioxolo[4',5':3,4]benzo[1,2-d][1,3]dioxin-4-yl)benzyl]phenol (34 mg, 0.08 mmol) was dissolved in methylene chloride (0.8 ml) and the mixture was stirred under ice cooling. To the mixture was added pyridine (15 mg, 0,19 mmol), 2-[N,N-bis(trifloromethyl)amino]pyridine (34 mg, 0,096 mmol)and then N,N-dimethylaminopyridine (1 mg), the reaction mixture was stirred at room temperature for 30 minutes and to the mixture was added water to stop the reactions. The mixture was extracted with methylene chloride and the organic layer was washed with water and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified preparative TLC [eluent=ethyl acetate:n-hexane (1:4)] to obtain specified in the title compound (37 mg, 83%).

1H-NMR (CDCl3) δ: 1,11-1,24 (1H, m), 1,4 (6H, C)was 1.43 (3H, s)of 1.53 (3H, s), 1,74 (1H, dt, J=13,7, 3,9 Hz), 1,80-of 1.93 (1H, m), 2,96 (1H, dt, J=l1,1, and 3.6 Hz), 3,59-to 3.92 (5H, m), 3,98 (2H, s), 7,00-7,03 (2H, m), 7,10-to 7.35 (6H, m)

(3) Synthesis of (3aS,4S,5aR,9aR,9bR)-4-[3-(4-cyclopropylmethyl)phenyl]-2,2,8,8-tetramethylhexadecane-[1,3]dioxolo[4',5':3,4]benzo[1,2-d][l,3]dioxin

In a stream of nitrogen to a mixture of 4-[3-((3aS,4S,5aR,9aR,9bR)-2,2,8,8-tetramethylhexadecane[l,3]dioxolo[4',5':3,4]benzo[1,2-d][1,3]dioxin-4-yl)benzyl]phenyl ester triftormetilfullerenov acid (38 mg, 0,068 mmol), K3PO4(65 mg, 0.31 mmol), sodium bromide (7 mg, 0,068 mmol), cyclopropylboronic acid (9 mg, 0.10 mmol) and Pd(PPh3)4(8.0 mg, to 0.007 mmol) was added to a mixture of toluene (0.5 ml)-water (0,017 ml) and the reaction mixture was heated at 100°C and was stirred for six hours. The reaction mixture was cooled to 0°C and the resulting mixture was added water. The resulting solution was extracted with ethyl acetate and the organic layer was washed saturated aqueous sodium chloride and dried over sodium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified preparative TLC [eluent=ethyl acetate:n-hexane(l:4)] to obtain specified in the title compound (10 mg, 33%).

1H-NMR (CDCl3) δ: of 0.62 and 0.68 (2H, m), 0,89-to 0.96 (2H, m), 1,10-1,24 (1H, m)of 1.42 (3H, s)of 1.43 (3H, s)of 1.46 (3Hf (C), and 1.54 (3H, s), 1,74 (1H, dt, J=13,7, 3,9 Hz), 1,80-of 1.93 (2H, m)to 2.94 (1H, dt, J=10,9, 3.6 Hz), 3,59-of 3.96 (8H, m), of 6.96-7,07 (7H, m), 7,16-of 7.25 (1H, m)

(4) Synthesis of (1R,2R,3S,4S,6R)-4-[3-(4-cyclopropylbenzene the l)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

A solution of (3aS,4S,5aR,9aR,9bR)-4-[3-(4-cyclopropylmethyl)phenyl)-2,2,8,8-tetramethylhexadecane[1,3]-dioxolo[4',5':3,4]benzo[1,2-d][l,3]dioxin (10 mg, of 0.022 mmol) in dioxane (0.2 ml) was cooled to 0°C and the resulting mixture was added dropwise 2 n hydrochloric acid (0.2 ml). The reaction mixture was stirred at the same temperature for three hours, then to the mixture was added saturated aqueous solution of sodium bicarbonate. The resulting solution was extracted with methylene chloride and the organic layer was washed saturated aqueous sodium chloride and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified preparative TLC [eluent=methanol:methylene chloride (1:10)] to obtain specified in the title compound (4.5 mg, 51%).

1H-NMR (CD3OD) δ: 0,63 of-0.68 (2H, m), 0,91-0,98 (2H, m), 1,42-of 1.52 (1H, m), 1,62-of 1.78 (1H, m), 1,80-of 1.94 (2H, m), 2,54-of 2.66 (1H, m), 3.33 and is 3.40 (2H, m), 3,50-3,68 (2H, m), with 3.79 (1H, DD, J=10,9, 3,9 Hz), 3,93 (2H, s), 6,85-7,16 (7H, m), 7,21-7,26 (1H, m)

MS (ESI+): 386 [M+H2O]+

Retention time HPLC: be 18.49 minutes

The measurement conditions for HPLC

Column: YMC-Pack ODS-A 6,h mm, 5 µm

Mobile phase: elution using a gradient from 10 mm AcONH4/H2O (95%) plus 10 mm AcONH4/MeOH (5%) up to 10 mm AcONH4/MeOH (100%) for 20 minutes, and then in the same conditions [10 mm AcONH4/MeOH (100%)] within five minutes

Soon the motion flow: 1.5 ml/min

The column temperature: room temperature

Conditions detection: the whole plot of the entire wavelength from 230 to 400 nm

Example 81

(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-forfinal]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

(1) Synthesis of (1R,2R,3S,4R,5R)- and (1S,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[5-(4-active compounds)-2-forfinal]cyclohexanol

In a stream of nitrogen a solution of n-utility in hexane (2,44 M, 0,368 ml) was added dropwise to a solution of 2-bromo-4-(4-active compounds)-1-fervently (to 0.263 g, 0,9000 mmol) in a simple ether (3.0 ml) at -78°C and the obtained mixed solution was stirred at the same temperature for two hours. To this solution was added a solution of 2,3,4-Tris-benzyloxy-5-methylcyclohexane (0,483 g to 0.900 mmol) in THF (1.5 ml) and the reaction mixture was stirred for two hours. The reaction was stopped by adding a saturated aqueous solution of ammonium chloride and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate)and the solvent is then drove away under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:4)] to obtain (1R)-isomer (0,117 g, 17.3%) and (1S)-isomer (0,311 g, 46.1 per cent) wannago in the connection header.

(1R)-isomer:1H-NMR (CDCl3) δ: 1,15-of 1.32 (3H, m), 1,81-of 1.92 (1H, usher.), 2,20-2,38 2H, user.), 2,62 (2H, square, J=9.8 Hz), of 3.07 (1H, usher.), 3,40-3,55 (1H, m), 3,66-of 3.80 (2H, m), 3,84-4,06 (4H, m), 4,28 (1H, d, J=12.3 Hz), of 4.45 (2H, s), 4,58 (2H, t, J=12.1 Hz), 4.80 to 4,96 (3H, m), 6,76-6,84 (2H, m), 6,86-7,00 (1H, m), 7,02-7,44 (23H, m), 7,52-of 7.60 (1H, m)

(1S)-isomer:1H-NMR (CDCl3) δ: of 1.13 (3H, t, J=1.5 Hz), 1,34-of 1.55 (1H, usher.), of 1.84 (1H, t, J=2.4 Hz), 2,50 (2H, square, J=1.5 Hz), a 2.75 (1H, DD, J=2,4, and 0.9 Hz), with 2.93 (1H, d, J=0.9 Hz), 3,37 (1H, DD, J=10,5, and 6.6 Hz), 3,57-of 3.78 (3H, m), 3,86-4,06 (3H, m), 4,40-5,00 (8H, m), 6,80-7,60 (26H, m), 7,72-to 7.84 (1H, m)

(2) Synthesis of (1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-forfinal]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

To a solution of (1R,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[5-(4-active compounds)-2-forfinal]cyclohexanol (271 mg, 0,361 mmol) in a solvent mixture of methanol-THF (1:1) (20 ml) was added catalyst a 20% palladium hydroxide (40 mg). The mixture was stirred in hydrogen atmosphere for 30 minutes, and then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=methanol:methylene chloride (1:10)] to obtain specified in the connection header (44,6 mg, 31,6%).

1H-NMR (CD3OD) δ: of 1.18 (3H, t, J=7.2 Hz), 1,15-of 1.26 (1H, m)to 1.48 (1H, DD, J=13,5, 13,2 Hz), to 2.57 (2H, square, J=7.8 Hz), 2,73 (1H, DD, J=13,5, 3.0 Hz), 3,30-of 3.80 (1H, m), 3,50 (1H, DD, J=9,9, 5.7 Hz), 3,53-3,66 (2H, m), 3,83-3,92 (3H, m)6,94 (1H, DD, J=12,3, 8.1 Hz), 7,00-of 7.25 (5H, m), 7,95 (1H, DD, J=7,8, 1.8 Hz)

MS (ESI+): 413 [M+Na]+

Retention time HPLC: 10.9 minutes

Example 82

(1S,2R,3S,4R,5R)-1-[5-(4-active compounds)2-forfinal]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol

To a solution of (1S,2R,3S,4R,5R)-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[5-(4-active compounds)-2-forfinal]cyclohexanol (33 mg, 0,044 mmol)obtained in Example 81, in a mixture of methanol-THF (1:1) (1,4 ml) was added catalyst a 20% palladium hydroxide (7.5 mg). The mixture was stirred in hydrogen atmosphere for 2.5 hours, then the catalyst was filtered. The solvent is kept under reduced pressure and the obtained residue was purified column chromatography on silica gel [eluent=methanol:methylene chloride (1:10)] to obtain specified in the title compound (17.5 mg, 100%).

1H-NMR (CD3OD) δ: of 1.18 (3H, t, J=7.5 Hz), 1.70 to to 1.79 (1H, m), 1,98-2,11 (2H, m), 2.57 m (2H, square, J=7.8 Hz), 3,32 is-3.45 (1H, m), 3,60-3,71 (3H, m), 3,90 (2H, s), of 3.94 (1H, d, J=9.0 Hz), 6,91 (1H, DD, J=12,3, 8,I, Hz), 7,02 for 7.12 (5H, m), 7,53 (1H, DD, J=7,8, 2,4 Hz)

MS (ESI+): 413 [M+Na]+

Retention time HPLC: 11.7 minutes

Example 83

(1R,2R,3S,4R,5R)-5-Hydroxymethyl-1-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3,4-tetraol

The target compound was obtained by the same steps as outlined in Example 81, using appropriate starting compounds and reagents.

1H-NMR (CD3OD) δ: 1,62-of 1.80 (2H, m), 1,94-2,10 (1H, m), 3,40 (1H, DD, J=10,5, and 8.7 Hz), 3,62-and 3.72 (4H, m), of 3.73 (3H, s)to 3.89 (2H, s)6,70-PC 6.82 (2H, m), 7,00-7,03 (2H, m), 7,06 for 7.12 (2H, m), 7,22 (1H, t, J=7.8 Hz), 7,27-to 7.32 (1H, m), 7,34-7,37 (1H, m)

MS (ESI+): 375 [M+H]+

Retention time HPLC: at 9.53 minutes

Example 84

(1S,2R,3S,4R,5R)-5-Hydroxym the Teal-1-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3,4-tetraol

The target compound was obtained by the same steps as outlined in Example 81, using appropriate starting compounds and reagents.

1H-NMR (CD3OD) δ: 1,28-of 1.44 (1H, m), and 1.56 (1H, t, J=13,2 Hz), 2,35 (1H, dt, J=13,5, 3,O Hz), of 3.45 (1H, DD, J=l1,1, 6.0 Hz), 3,60-3,70 (3H, m), of 3.73 (3H, s)to 3.89 (2H, s), 6,77-PC 6.82 (2H, m), 7,00-7,05 (1H, m), 7,06-7,13 (2H, m), 7,20 (1H, t, J=7.8 Hz), 7,60-the 7.65 (1H, m), 7.68 per-of 7.70 (1H, m)

MS (ESI+): 397 [M+Na]+

Retention time HPLC: 14.6 minutes

Example 85

(1R,2R,3S,4S,6R)-4-[l-(4-active compounds)-1H-indol-3-yl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

(1) Synthesis of 1-(4-active compounds)-1H-indole

To a solution of indole (4.0 g, to 34.1 mmol) was added a solution of potassium hydroxide (2,40 g of 42.6 mmol) in ethanol (200 ml) and the resulting mixed solution was stirred at room temperature for two hours. The solvent is kept at reduced pressure. The residue was dissolved in acetone (200 ml) and the resulting mixture was added 1-chloromethyl-4-ethylbenzene (5,28 g, to 34.1 mmol). The reaction mixture was stirred at room temperature all day and night, and then was subjected to filtration through celite and the filtrate was subjected to distillation under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:500)] to obtain specified in the title compound (3.8 g, 47%).

1H-NMR (CDCl3) δ: 1,19 (3H, t, J=7,6 Hz), 2,60 (2H, square, J=7.6 G is), at 5.27 (2H, s), 6,53 (1H, DD, J=3.1 and 0.7 Hz), 7,03 (2H, d, J=7,6 Hz), 7,07-7,22 (5H, m), 7,29 (1H, d, J=8.0 Hz), to 7.64 (1H, d, J=6,8 Hz)

(2) Synthesis of 3-bromo-1-(4-active compounds)-1H-indole

A solution of 1-(4-active compounds)-1H-indole (2.0 g, 8.50 mmol) in DMF (20 ml) was added dropwise at room temperature to a solution of bromine (and 0.46 ml, 8,93 mmol) in DMF (20 ml). The reaction mixture was stirred for two hours and then was poured into ice water solution of persulfate sodium. The resulting mixture was extracted with ethyl acetate and the organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride and was dried (anhydrous magnesium sulfate), the solvent is then drove away under reduced pressure. The residue was recrystallized from ethyl acetate and n-hexane to obtain specified in the title compound (1.68 g, 63%).

1H-NMR (CDCl3) δ: of 1.20 (3H, t, J=7,6 Hz), 2,61 (2H, square, J=7,6 Hz), 5,23 (2H, s), 7,05 (2H, DD, J=8.0 Hz), 7,11-7,22 (5H, m), 7,30 (1H, DD, J=6,5, 1.9 Hz), EUR 7.57 (1H, DD, J=6,5, 1.9 Hz)

(3) Synthesis of (2R,3S,4R,5R)-2,3,4-trebaseleghe-5-benzoyloxymethyl-1-[1-(4-active compounds)-1H-indol-3-yl]-cyclohexanol

In a stream of nitrogen a solution of 3-bromo-1-(4-active compounds)-1H-indole (427 mg, of 1.36 mmol) in THF (8 ml) was cooled to -78°C and the resulting mixture was added a solution of n-utility in hexane (1,6 M 0,89 ml of 1.43 mmol). The reaction mixture was stirred at the same temperature for five minutes. To this solution was added the drop wise addition of a solution of (2R,3S,4R,5R)-2,3,4-trebaseleghe-5-(benzoyloxymethyl)cyclohexanone (875 mg, of 1.63 mmol) in THF (5.6 ml) and the mixture was stirred at -78°C for two hours. The reaction was stopped by adding a saturated aqueous solution of ammonium chloride. The resulting mixture was extracted with ethyl acetate and the organic layer was washed with water and then dried over sodium sulfate. The residue obtained by removal of the solvent, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:10)] to obtain the less polar isomer (354 mg, 34%) and more polar isomer (115 mg, 11%) specified in the connection header.

Less polar isomer:1H-NMR (CDCl3) δ: of 1.18 (3H, t, J=7.2 Hz), of 1.93 (2H, m), is 2.40 (1H, m), 2,61 (2H, square, J=7,2 Hz), 3,40-5,22 (15H, m), 7,02-7,40 (28H, m), to 7.93 (1H, d, J=8.0 Hz)

More polar isomer:1H-NMR (CDCl3) δ: of 1.18 (3H, t, J=7,6 Hz), is 2.40 (1H, m), of 2.38 (2H, m), 2,58 (2H, square, J=7,6 Hz), 3,41-5,24 (15H, m), 6,83 (1H, d, J=8.0 Hz), 7.03 is-7,34 (27H, m), of 7.75 (1H, d, J=7,6 Hz)

(4) Synthesis of 1-(4-active compounds)-3-[(1S,2S,3R,4R,5R)-2,3,4-trebaseleghe-5-(benzyloxyethyl)cyclohexyl]-1H-indole

In a stream of nitrogen triethylsilane (of 0.21 ml, 1,22 mmol) was added dropwise to a solution of (2R,3S,4R,5R)-2,3,4-tribonacci-5-benzoyloxymethyl-1-[1-(4-active compounds)-1H-indol-3-yl]cyclohexanol (469 mg, 0.61 mmol) in methylene chloride (6 ml) at 0°C. To the mixture was added dropwise within five minutes the complex of boron TRIFLUORIDE-diethyl ether (0,093 ml, 0.73 mmol) and the reaction mixture was stirred at 0°C for two hours. To the reaction the mixture was added saturated aqueous sodium hydrogen carbonate solution and the resulting mixture was extracted with methylene chloride. The organic layer was washed saturated aqueous sodium chloride and dried over sodium sulfate. The residue obtained by removal of the solvent under reduced pressure, was purified column chromatography on silica gel [eluent=ethyl acetate:n-hexane (1:15)] to obtain specified in the title compound (232 mg, 51%).

1H-NMR (CDCl3) δ: 1,17 (3H, t, J=7,6 Hz)to 1.87 (2H, m), and 2.27 (1H, m), 2,58 (2H, square, J=7,6 Hz)to 3.36 (1H, DD, J=9,0, 1.7 Hz), 3,59-3,70 (2H, m), 3,88-4,00 (2H, m), of 4.12 (1H, t, J=8.6 Hz), to 4.38 (2H, s), 4,47 (1H, d, J=of 11.4 Hz), of 4.54 (1H, d, J=2.7 Hz), 4,58 (1H, d, J=3.1 Hz), 4,80 (1H, d, J=10,7 Hz), 4,89 (1H, d, J=10,7 Hz), to 4.98 (1H, d, J=10,7 Hz in), 5.25 (2H, d, J=4.9 Hz), 6,97 (2H, d, J=8,4 Hz), 7,05 (2H, d, J=8.0 Hz), 7,08-7,35 (24H, m), a 7.62 (1H, d, J=7,2 Hz)

(5) Synthesis of (1R,2R,3S,4S,6R)-4-[1-(4-active compounds)-1H-indol-3-yl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol

In a stream of nitrogen dimethyldisulfide (0,72 ml) and a complex of boron TRIFLUORIDE-diethyl ether (of 0.36 ml, 2.8 mmol) was added under ice cooling to a solution of 1-(4-active compounds)-3-[(1S,2S,3R,4R,5R)-2,3,4-Tris-benzyloxy-5-(benzoyloxymethyl)-cyclohexyl]-1H-indole (213 mg, 2.28 mmol) in methylene chloride (4,7 ml). The obtained mixed solution was stirred at room temperature for 64 hours, then to the resulting mixture under ice cooling was added water and the resulting solution was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride and was dried (anhydrous magnesium sulfate, then the solvent from anjali under reduced pressure. The obtained residue was purified column chromatography on silica gel [eluent=dichloromethane; methylene chloride:methanol (50:1)] to obtain specified in the title compound (45 mg, 41%).

1H-NMR (CD3OD) δ: 1,17 (3H, t, J=7,6 Hz)of 1.66 (1H, m)to 1.79 (1H, m)of 2.16 (1H, m), 2,58 (2H, square, J=7,6 Hz)to 3.33 (1H, m), of 3.57 (1H, DD, J=10,7, 6,I, Hz)of 3.69 (1H, DD, J=10,7, 4,2 Hz), 3,76-3,88 (3H, m), from 5.29 (2H, ), 6,98-7,11 (6H, m), 7,24 (1H, d, J=8.0 Hz), 7,30 (1H, s), a 7.62 (1H, d, J=7,6 Hz)

MS (ESI+): 396 [M+H]+

Structural formulas of the compounds of the above Examples are shown in Table 1-Table 10.

Experimental Example 1

Test to confirm the inhibitory effect on Na+-glucose cotransporter person (SGLT1 and SGLT2)

(1) preparation of expression vector of human SGLT1

PCR was performed using KOD+DNA polymerase (product of the company Toyobo Co., Ltd.), where the matrix used a cDNA library isolated from the small intestine of man (the product of the company Clontech), using synthetic DNA primers for amplification of cDNA human SGLT1. For the eat amplificatory fragment cloned into the vector pcRII-Topo using a set of Topo TA Cloning Dual Promoter kit (product of the company Invitrogen) and introduced into competent cells of E. coli(TOP10, the product of the company Invitrogen), and clones that showed resistance to ampicillin, proliferated in LB medium containing ampicillin (50 mg/l). Using the normal way of prooperirovano E. coli was purified plasmid (see Maniatis et al., Molecular Cloning). This plasmid was taken as template and PCR was carried out using KOD+DNA polymerase using a synthetic DNA primer, which included the recognition sites of restriction enzyme for amplification of cDNA SGLT1 human (fragment added to the site EcoRI recognition to the left and website recognition Hind III to the right). This amplificatory fragment was subjected to cleavage EcoRI and Hind III and splintered fragments associated with the recognition sites of the expression vector rdnc 3,1(-) (product of the company Invitrogen) using the kit Rapid DNA Ligation (product company Roche Diagonostic). The associated expression vector was introduced into competent cells ofE. coli(DH5α, a product of the company Invitrogen) and proliferated in ampicillin-containing LB medium with getting SGLT1 expression vector in accordance with a customary method.

(2) Obtaining the expression vector of human SGLT2

PCR was performed using KOD+DNA polymerase, which was used as a matrix library cDNA isolated from human kidney (a product of the company Clontech), using synthetic DNA primers for amplification of DVS is SGLT2 person. Then amplificatory fragment cloned into the vector pcRII-Topo using a set of Topo TA Cloning Dual Promoter and introduced into competent cells ofE. coli(TOP10), and clones that showed resistance to ampicillin, proliferated in LB medium containing ampicillin (50 mg/l). Using the normal way of prooperirovano E. coli was purified plasmid. This plasmid was taken as template and PCR was carried out using KOD+DNA polymerase using a synthetic DNA primer, which included the recognition sites of restriction enzyme for amplification of cDNA human SGLT2 (fragment added with site recognition Xho I left and website recognition Hind III to the right). This amplificatory fragment was subjected to cleavage Xho I and Hind III and splintered fragments associated with the recognition sites of the expression vector rdnc 3,1(-) using the kit Rapid DNA Ligation. The associated expression vector was introduced into competent cells ofE. coli(DH5α) and proliferated in ampicillin-containing LB medium with getting SGLT2 expression vector in accordance with a customary method.

(3) Obtaining cells stably expressing human SGLT1, and cells stably expressing human SGLT2

The expression vector of human SGLT1 and SGLT2 expression vector human cleaved by restriction enzyme Pvu I, was introduced into cells CHO-K1 when p is power FuGene (product company Roche Diagonostics). After the introduction of a gene, the cells were incubated in DMEM (product of the company Gibco)containing penicillin (50 Units/ml, a product of the company Sigma), streptomycin (50 mg/l, the product of the company Sigma), Geneticin (200 mg/l, the product of the company Nakalai Tesque) and 20% fetal bovine serum, in the presence of 5% CO2at 37°C for approximately three weeks, to get Genticin-resistant clones. Of these clones were selected and received cells stably Express human SGLT1, and cells capable of stably Express the human SGLT2, using as indicator the sodium-dependent active uptake of sugar (methyl-α-D-glucopyranoside).

(4) Measurement of the activity of inhibiting the uptake of methyl-α-D-glucopyranoside

Cells stably expressing human SGLT1 or cells stably expressing human SGLT2, were sown in 96-well plates to a density of 30,000 - 40,000 cells/well and incubated over time from four to six days. Then the cultural environment of the tablet was removed and added to the buffer for pre-treatment (a buffer containing 140 mm holdingarea, 2 mm potassium chloride, 1 mm calcium chloride, 1 mm magnesium chloride, 10 mm 2-[4-(2-hydroxyethyl)-1-piperazinil]econsultancy acid and Tris(hydroxymethyl)-aminomethane, and having pH = 7,4) in the amount of 150 μl per well, and then left to stand at 37°C for 20 minutes. A buffer for preventing the preliminary processing was removed and was again added to the buffer for pre-treatment in the amount of 50 μl per well, and then left to stand at 37°C for 20 minutes. To 100 ml of a buffer (a buffer containing 140 mm sodium chloride, 1 mm potassium chloride, 1 mm magnesium chloride, 1 mm methyl-α-D-glucopyranoside, 10 mm 2-[4-(2-hydroxyethyl)-1-piperazinil]econsultancy acid and Tris(hydroxymethyl)aminomethane, and having pH = 7,4) was added and mixed with it to 6.3 ml of methyl-α-D-(U-14C)glucopyranoside (200 MCI/l, the product of the company Amersham Pharmacia Biotech) to obtain absorbing buffer, the test compound was dissolved in this absorbing buffer and the resulting solution was used as a buffer to determine the inhibitory activity. In addition, as a control was used absorbing buffer that does not contain the test compound. In addition, to determine the underlying absorption in the absence of the test compound and sodium was obtained in the same way basic absorbing buffer containing 140 mm holdingarea instead of sodium chloride and used for the determination. Buffer for pre-treatment was removed from the wells of the culture of the tablet and was added to the buffer to determine the inhibitory activity of 35 µl per well and left to stand at 37°C for 45 minutes. Then the buffer to determine the inhibitory activity was removed and added to wash buffer (buffer solution containing 140 mm holdingarea, 2 mm chloride is potassium, 1 mm calcium chloride, 1 mm magnesium chloride, 10 mm methyl-α-D-glucopyranoside, 10 mm 2-[4-(2-hydroxyethyl)-1-piperazinil]econsultancy acid and Tris(hydroxymethyl)aminomethane, and having pH = 7,4) in the amount of 300 μl per well and immediately removed. This washing operation was repeated again and added solubilizers cell solution (1 M sodium hydroxide and 0.1% sodium lauryl) in quantities of 30 μl per well to solubilize the cells. To the resulting solution was added 15 μl of 2 M hydrochloric acid, and 40 μl of the obtained solution was transferred to a plate Luma (product of Packard company) and left to stand overnight at room temperature to evaporate the solvent. The radioactivity of the sample on the plate was determined using a Topcount (manufacturer Packard company). The concentration of the test compounds (value IR50), which inhibited 50% of absorption, where the value obtained by subtracting the baseline absorption of the absorption control, taken as 100%, was calculated on the basis of the curve of concentration-inhibition using arithmetic program (Elfit, ver.3). In the compounds of the present invention showed a remarkable effect on the inhibition of SGLT2. Values IR50for inhibition of SGLT2 obtained for representative compounds of the present invention are presented in the ENES in Table 11.

Table 11
Test connectionValue IR50(nm)Test connectionValue IR50(nm)
Example 161Example 598,9
Example 2111Example 627,1
Example 87Example 646,6
Example 1114Example 6818
Example 1218Example 695,1
Example 2531Example 707,4
Example 427,7Example 7311
Example 446 Example 5414
Example 5517

Industrial applicability

The present invention can be provided cyclohexane compounds that show activity on the inhibition of SGLT2 activity, or their pharmaceutically acceptable salts. Compounds of the present invention are useful as preventive or therapeutic agents for diabetes, diabetes-related diseases or diabetic complications.

1. The compound represented by formula (I):
Formula 1
,
where a represents-O-;
n is an integer selected from 0 and 1;
R6and R7each independently represents a hydrogen atom or a C1-C6alkyl group,
m is an integer selected from 1-3;
Q is selected from Q1-Q5represented by the following formula:
Formula 2


where R1, R2, R3and R4each independently selected from a hydrogen atom, hydroxy-group and benzyloxy;
R5in the bran from a hydrogen atom and a hydroxy-group;
Ar1represents fenelonov group or a 5,6-membered heteroarenes group containing one heteroatom selected from a nitrogen atom and sulfur atom, where heteroarenes group may form a condensed ring with a benzene ring, and Ar1may be substituted by one or more Rb;
Ar2represents a phenyl group, benzothiazoline group, benzodioxolyl group or 2,3-dihydrobenzofuranyl group, and Ar2may be substituted by one or more Rb;
Rb, each independently selected from C1-C6alkyl group which may be substituted by one or more Rc, C1-C6alkenylphenol group which may be substituted by one or more Rc, C3-C3cycloalkyl group, halogen atom, hydroxy-group, ceanography, C1-C6alkoxygroup, which may be substituted by one or more Rc, a 5-membered heteroaryl group containing two nitrogen atom, C1-C6allylthiourea, C1-C6alkylsulfonyl group, C1-C6alkylcarboxylic group, -CO2Ri, and-CONRiRj;
Rc each independently selected from a halogen atom and an amino group;
Ri and Rj each independently selected from a hydrogen atom and C1-C6alkyl group,
or its pharmaceutically acceptable salt.

2. With the unity according to claim 1, where n has a value of 1, or its pharmaceutically acceptable salt.

3. The compound according to claim 1, where the Deputy -(CR6R7)m-Ar2associated with the ring atom, which is adjacent to the ring atom bound to the Deputy And Ar1or its pharmaceutically acceptable salt.

4. The compound according to claim 1, where n is 0, or its pharmaceutically acceptable salt.

5. The compound according to claim 4, where the Deputy -(CR6R7)m-Ar2associated with the second ring atom relative to the ring atom bound to Q in Ar1or its pharmaceutically acceptable salt.

6. The compound according to claim 1, where m has a value of 1, or its pharmaceutically acceptable salt.

7. The compound according to claim 1, where Ar1represents fenelonov group, thienylene group, pyridinylamino group or Intellinova group, where these groups may be substituted by one or more Rb, or its pharmaceutically acceptable salt.

8. The compound according to claim 1, where each R1, R2, R3, R4and R5represents a hydroxy-group, or its pharmaceutically acceptable salt.

9. The compound according to claim 1, where m is 1; n is 1; Ar1represents fenelonov group, thienylene group, pyridinylamino group or Intellinova group, where these groups may be substituted one or the several Rb; and each R1, R2, R3, R4and R5represents a hydroxy-group,
or its pharmaceutically acceptable salt.

10. The compound according to claim 1, where m is 1; n is 0; Ar1represents fenelonov group, thienylene group, pyridinylamino group or Intellinova group, where these groups may be substituted by one or more Rb; and each R1, R2, R3, R4and R5represents a hydroxy-group,
or its pharmaceutically acceptable salt.

11. A compound selected from the following groups:
[2-(4-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[1S,2R,3R,4R,6S]-4-hydroxymethyl-6-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3-triol;
[2-(4-cryptomaterial)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-cyclopentylmethyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-Chlorobenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
(2-benzoylphenyl)-5A-carb-β-D-glucopyranoside;
[2-(4-isopropylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-cyclopropylmethyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-n-propylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-trifloromethyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methylsulfonylbenzoyl)phenyl]-5A-carb-β-D-glucopyranoside;
[3-fluoro-2-(4-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(3-trifloromethyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxybenzyl)-4-were]-5A-carb-β-D-glucopyranoside;
[2-(3-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxybenzyl)-4-methoxyphenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxybenzyl)-6-were]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxybenzyl)-4-forfinal]-5A-carb-β-D-glucopyranoside;
[2-(3-terbisil)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(3-methylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[5-fluoro-2-(4-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methylsulfonylbenzoyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-terbisil)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(3,4-dimethoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-active compounds)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-hydroxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-cyanobenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(3-cryptomaterial)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-aminomethylbenzoic)phenyl]-5A-carb-β-D-glucopyranoside;
[5-methoxy-2-(4-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxycarbonylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-carbamoylmethyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-N,N-dimethylcarbamoyl)phenyl]-5a-carb-β-D-glucopyranoside;
[2-(4-ethoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-deformational)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-tert-butylbenzyl)the dryer is l]-5A-carb-β-D-glucopyranoside;
[2-(4-methylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxybenzyl)phenyl]-5-triptorelin-3-yl]-5A-carb-β-D-glucopyranoside;
[3-methoxy-2-(4-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxybenzyl)-3-were]-5A-carb-β-D-glucopyranoside;
[2-(3-fluoro-4-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[4-(4-cyclopropylmethyl)pyridine-3-yl]-5A-carb-β-D-glucopyranoside;
[2-(4-carboxybenzoyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-vinylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
{2-[4-(2,2-defermined)benzyl]phenyl}-5A-carb-β-D-glucopyranoside;
[2-(2,3-dihydrobenzofuran-5-ylmethyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(3-fluoro-4-methylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxy-3-methylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-(pyrazole-1-ylbenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(3-chloro-4-methoxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(3,4-methylenedioxybenzyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-cyclobutylmethyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-acetylphenyl)phenyl]-5A-carb-β-D-glucopyranoside;
[2-(4-methoxybenzyl)-5-were]-5A-carb-β-D-glucopyranoside;
[2-(4-active compounds)thiophene-3-yl]-5A-carb-β-D-glucopyranoside;
[2-(benzothiophen-2-yl)were]-5A-carb-β-D-glucopyranoside;
(R)-{2-[1-(4-cyclopropylmethyl)ethyl]phenyl}-5a-carb-β-D-glucopyranoside;
(S)-{2-[1-(4-cyclopropylmethyl)e is Il]phenyl}-5A-carb-β-D-glucopyranoside;
[2-(4-cyclopropylmethyl)-5-methylthiophene-3-yl]-5A-carb-β-D;
[2-(4-active compounds)-5-methylthiophene-3-yl]-5A-carb-β-D-glucopyranoside;
[5-chloro-2-(4-cyclopropylmethyl)thiophene-3-yl]-5A-carb-β-D-glucopyranoside;
(1R,2S,3R,6R)-6-[2-(4-cyclopropylmethyl)phenoxy]-4-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol;
(1R,2S,3R,6R)-4-hydroxymethyl-6-[2-(4-methoxybenzyl)-phenoxy]cyclohex-4-ene-1,2,3-triol;
(1R,2S,3S,6R)-4-[3-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohex-4-ene-1,2,3-triol;
(1R,2R,3S,4R,5R)-1-[3-(4-active compounds)-4-methoxyphenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1R,2R,3S,4S,6R)-4-[3-(4-active compounds)-4-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4R,5R)-1-[2-ethoxy-5-(4-active compounds)phenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1R,2R,3S,4S,6R)-4-[2-ethoxy-5-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2,4-acid]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2,4-acid]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-were]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-were]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-methoxyphenyl]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-t is eformatexif]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1R,2R,3S,4S,6R)-4-[5-(4-isopropylbenzyl)-2-methoxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4S,6R)-4-[3-(4-active compounds)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4S,6R)-4-[3-(4-hydroxybenzyl)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4S,6R)-4-[5-(4-active compounds)-2-hydroxyphenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4S,6R)-4-[3-(4-cyclopropylmethyl)phenyl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol;
(1R,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-forfinal]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1S,2R,3S,4R,5R)-1-[5-(4-active compounds)-2-forfinal]-5-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol;
(1R,2R,3S,4R,5R)-5-hydroxymethyl-1-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3,4-tetraol;
(1S,2R,3S,4R,5R)-5-hydroxymethyl-1-[3-(4-methoxybenzyl)-phenyl]cyclohexane-1,2,3,4-tetraol; and
(1R,2R,3S,4S,6R)-4-[1-(4-active compounds)-1H-indol-3-yl]-6-(hydroxymethyl)cyclohexane-1,2,3-triol,
or its pharmaceutically acceptable salt.

12. Pharmaceutical composition comprising a compound according to any one of claims 1 to 11, which is used as an inhibitor of Na+-glucose cotransporter (SGLT2).

13. Pharmaceutical composition comprising a compound according to any one of claims 1 to 11, which is used for the prevention or treatment of diabetes, diabetic complications caused by hyperglycemia, or obesity.

14. The pharmaceutical composition according to item 13, where diabetes is an insulin-dependent diabetes the diabetes (diabetes type I) or insulin-independent diabetes mellitus (type II diabetes).

15. A method of prophylaxis or treatment of diabetes, such as insulin-dependent diabetes mellitus (diabetes type I) or insulin-independent diabetes mellitus (type II diabetes), diabetic complications caused by hyperglycemia, or obesity, comprising administration to the patient a therapeutically effective amount of a compound according to any one of claims 1 to 11.



 

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FIELD: chemistry.

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(5) ,

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10 cl, 2 tbl, 39 ex

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R8, R9, R11, R12- H, lower alkyl, halogen, HE, CF3,

R3-

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< / BR>
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< / BR>
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15 cl, 32 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of aniline of the general formula (I): and their pharmaceutically acceptable salts and isomeric forms possessing properties of phosphodiesterase-4 inhibitors. Compounds can be used, fore example, for enhancing cognitive ability. In compounds of the general formula (I) R1 means linear or branched (C1-C4)-alkyl that can be unsubstituted or substituted with one or more halogen atoms; R2 means linear or branched (C1-C4)-alkyl that can be unsubstituted or substituted with one or more substitutes of the following order: halogen atom, (C1-C4)-alkoxy or their combinations, (C3-C10)-cycloalkyl, (C4-C16)-cycloalkylalkyl wherein alkyl fragment comprises from 1 to 4 carbon atoms, (C7-C11)-arylalkyl wherein aryl fragment comprises 6 carbon atoms, and alkyl fragment that can be linear or branched and comprises from 1 to 5 carbon atoms and wherein radical arylalkyl can be unsubstituted or substituted in aryl fragment with one or more substitutes of the following order: halogen atom, alkoxy group comprising from 1 to 4 carbon atoms or their combinations, and in alkyl fragment one group -CH2CH2- is optionally replaced for group -CH=CH-, and one group -CH2- is optionally replaced for -O- for -NH-, partially unsaturated carbocyclic group comprising from 5 to 9 carbon atoms that can comprise condensed benzene ring, heterocyclic group that can be saturated, partially saturated or unsaturated and comprises from 5 to 6 carbon atoms in cycle including one atom chosen from oxygen (O), or heterocyclylalkyl group wherein heterocyclic fragment can be saturated, partially saturated or unsaturated and comprises from 5 to 6 carbon atoms in cycle including 1-2 atoms chosen from nitrogen (N) or sulfur (S) atoms, and alkyl fragment that can be linear or branched comprises from 1 to 5 carbon atoms; R3 means partially unsaturated carbocyclylalkyl group wherein carbocyclic fragment comprises from 5 to 6 carbon atoms, and linear or branched alkyl fragment comprises from 1 to 5 carbon atoms, (C7-C11)-arylalkyl wherein aryl fragment comprises 6 carbon atoms, and linear or branched alkyl fragment comprises from 1 to 5 carbon atoms and wherein arylalkyl radical can be linear or substituted in aryl fragment with one or more substitutes of the following group: trifluoromethyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or their combinations, heterocyclylalkyl group wherein heterocyclic fragment can be aromatic, partially or completely saturated and comprises from 5 to 10 atoms in cycle including 1-2 atoms chosen from N, O or S, and linear or branched alkyl fragment comprises from 1 to 5 carbon atoms and wherein heterocyclylalkyl group can be linear or substituted in heterocyclic fragment with one or more substitutes of the following order: halogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxy or their combinations; R4 means (C6-C12)-aryl that can be linear or substituted with one or more substitutes of the following order: halogen atom, (C1-C4)-alkyl, (C2-C4)-alkenyl, hydroxy, (C1-C4)-alkoxy, (C2-C4)-alkoxyalkoxy, nitro, trifluoromethyl, -OCF3, amino group, aminoalkyl, aminoalkoxy, hydroxy-(C1-C4)-alkyl, hydroxamic acid, tetrazol-5-yl, 2-(heterocyclyl)-tetrazol-5-yl, carboxy, alkoxycarbonyl, cyano, acyl, alkylsulfonyl, phenoxy, trialkyloxy, R5-L or their combinations, or heteroaryl comprising from 5 to 10 atoms in cycle including 1-2 atoms chosen from N wherein heteroaryl can be linear or substituted with one or more substitutes of the following order: (C1-C4)-alkyl, (C1-C4)-alkoxy, carboxy, alkoxycarbonyl or their combinations; R5 means hydrogen atom, (C1-C8)-alkyl, (C3-C10)-cycloalkyl, C6-aryl, heterocyclic group that can be saturated, partially saturated or unsaturated and comprises from 5 to 10 atoms in cycle from which at least atom means N or O, and wherein heterocyclic group can be linear or substituted with one or more (C1-C4)-alkyls, or group heterocyclylalkyl, and others. Also, invention relates to intermediates compounds and to a method for enhancing the cognitive ability.

EFFECT: valuable biological and biochemical property of compounds.

49 cl, 8 sch, 26 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy, chemical-pharmaceutical industry.

SUBSTANCE: invention relates to derivatives of aminodicarboxylic acids of the general formula (I) and a medicinal agent able to stimulate activity of soluble guanylate cyclase being independently of the presence of the heme group comprising in it and able to cause relaxation of vessels and comprising at least one compound of the general formula (I). Agent is designated for treatment of cardiovascular diseases and for treatment of the central nervous system diseases characterizing by disorder of the system NO/cGMP, and shows high bioavailability and effectiveness.

EFFECT: improved and valuable medicinal properties of agent.

7 cl, 232 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):

and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:

wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

22 cl, 1 tbl, 2 sch, 78 ex

The invention relates to compounds of General formula (I)

in which R1means a hydrogen atom, a radical, CH3or the radical (CH2HE; R2means the radical (CH2HE; X-Y represents a relationshiporZ indicates cycle selected among the cycles of the following formulas:

; R3means alkyl chain with 4 to 8 carbon atoms, substituted by one or more hydroxyl groups and, in addition, possibly substituted by one or more lower alkyl groups and/or substituted by one or more halogen atoms and/or substituted by one or more groups of CF3and/or in which one or a few simple links of the chain may be substituted with one or more double bonds, and R3is a cycle in the para - or meta-position relative to the link X-Y, as well as optical and geometrical isomers of the above compounds of formula (I)

The invention relates to new derivatives of balkanov General formula (A)

< / BR>
where Ar is phenyl which may be unsubstituted or substituted one, two or three substituents independently chosen among Cl, Br, F, -OMe, NO2, CF3C1-4lower alkyl, -NMe2, -NEt2, -SCH3, -NHCOCH3; 2-thienyl, 2-furyl; 3-pyridyl; 4-pyridyl or 3-indolyl; R-OCH2R1where R1choose from a number of-CH= CME2The CME=CH2-The CCH; provided that when Ar is a phenyl,4-alkylphenyl, 4-methoxyphenyl or 3,4-acid, R can be any except 3-methyl-2-butenyloxy

-diketones and ketoesters" target="_blank">

The invention relates to the chemistry of adamantane derivatives, and in particular to a new method of obtaining-dicarbonyl derivatives of adamantane General formula

< / BR>
where R=CH3:R1=CH3OC2H5; R=C6H5: R1=OC2H5C6H5, CF2H

R=CF3:R1=C6H5n-C6H4C1

< / BR>
< / BR>
which are the products for the synthesis of biologically active substances

The invention relates to a new therapeutic drug for diabetes and includes the compound of the formula I: R1-C(O)-C(R2')(R2)-X-C(O)-R3where X represents a group of formula-C(R4)(R5)-, -N(R6)-, -O-; where R4is a hydrogen atom, a C1-C5alkyl, carboxy, phenyl, C2-C5acyl, C2-C5alkoxycarbonyl, R5is a hydrogen atom, a C1-C5alkyl; R6is hydrogen; R1is phenyl, optionally substituted C1-C5by alkyl, hydroxy, hydroxyalkyl, C2-C6alkenyl, acyl, carboxy, teinila, C3-C7cycloalkyl; biphenyl, optionally substituted C1-C5the alkyl or hydroxy; naphthyl; terphenyl; C3-C7cycloalkyl, optionally substituted C1-C5the alkyl or phenyl; optionally substituted C1-C5alkyl; pyridyl; sensational; substituted; indanyl; fluorenyl or group; R2is hydrogen, C1-C5alkyl, optionally substituted by carboxy; R2'is hydrogen; R3- C1-C5alkyl, optionally substituted by phenyl or C1-C4alkoxy, C1-C4alkoxy; hydroxy; phenyl; C3-C72)2-; R2and R5taken together, form a simple bond or-CH2-, - (CH2)3-, -(CH2)4-; R2, R2', R4and R5taken together form =CH-CH=CH-CH=; R2' and R3taken together form a-CH(R8)-OH, -CH(R8)-CH(R9)-, -CH(R8)NH; R8and R9is hydrogen, and pharmaceutically acceptable salts

FIELD: chemistry.

SUBSTANCE: invention relates to new substituted phenoxy-aceitic acids (I), in which: X is halogen, cyano, nitro or C1-4alkyl, which is substituted with one or more halogen atoms; Y is chosen from hydrogen, halogen or C1-C6alkyl, Z is phenyl, naphthyl or ring A, where A is a six-member heterocyclic aromatic ring containing one or two nitrogen atoms, or can be 6,6- or 6,5-condensed bicycle which contains one O, N or S atoms, or can be 6,5-condensed bicycle which contains two O atoms, where phenyl, naphthyl or ring A can all be substituted with one or more substitutes, independently chosen from halogen, CN, OH, nitro, COR9, CO2R6, SO2R9, OR9, SR9, SO2NR10R11, CONR10R11, NR10R11, NHSO2R9, NR9SO2R9, NR6CO2R6, NR9COR9, NR6CONR4R5, NR6SO2NR4R5, phenyl or C1-6alkyl, where the last group can possibly be substituted with one or more substitutes, independently chosen from halogen; R1 and R2 independently represent a hydrogen atom or C1-6alkyl group, R4 and R5 independently represent hydrogen, C3-C7cycloalkyl or C1-6alkyl, R6 is a hydrogen atom of C1-6alkyl; R8 is C1-4alkyl; R9 is C1-6alkyl, possibly substituted with one or more substitutes, independently chosen from halogen or phenyl; R10 and R11 independently represent phenyl, 5-member aromatic ring which contains two heteroatoms, chosen from N or S, hydrogen, C3-C7cycloalkyl or C1-6alkyl, where the last two groups are possibly substituted with one or more substitutes, independently chosen from halogen or phenyl; or R10 and R11 together with the nitrogen atom to which they are bonded, can form a 3- to 8-member saturated heterocyclic ring, which possibly contains one or more atoms chosen from O, S(O)n (where n= 0, 1 or 2), NR8.

EFFECT: invention relates to a method of modulating activity of CRTh2 receptors, involving administration of therapeutically effective amount of formula compound or its pharmaceutically acceptable salt to a patient.

9 cl, 170 ex

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