Pharmaceutical compositions and triterpene derivatives

 

(57) Abstract:

Describes the new pharmaceutical composition for treating hepatitis comprising as an active ingredient triterpene derivative of the General formula I or its salt, where1represents a hydroxyl group, kilmetros, lower alkoxy or lower alkanoyloxy; R2is lower alkenyl, -CH2OR5where R5represents a hydrogen atom, arylmethyl, lower alkyl or lower alkanoyl, formyl, -COOR6where R6represents a hydrogen atom or lower alkyl, or-CH2N(R7R8where R7and R8that may be the same or different, represent a hydrogen atom, lower alkyl, aryl or lower alkanoyl; or R1and R2can be connected to each other to form - O-C(R9R10-O-CH2- where R9and R10that may be the same or different, represent lower alkyl or aryl; R3and R4that may be the same or different, represent a hydrogen atom, hydroxyl group, hydroxymethyl, -N(R11R12where R11and R12represent the lowest alkanoyl, -OR13where R13represents lower alkyl, alxn2. Fit new triterpene derivatives. 8 C. and 26 C.p. f-crystals, 1 tab., Il.

The scope of the invention

This invention relates to pharmaceutical compositions against liver diseases, including triterpene derivatives or their salts as the active ingredient. This invention also relates to a new triterpene derivative.

Background of the invention

The liver is an important organ that has various functions necessary to sustain life in a living organism, such as detoxification, different metabolisms and accumulation of substances. It is, however, often suffers from acute or chronic viruses, drugs, alcohol, and other factors. This causes viral hepatitis, drug hepatopathy, alcohol hepatopathy, fatty degeneration of the liver and, in addition, diseases such as cirrhosis and liver cancer. For the treatment of liver diseases is still used nutritional therapy, rest cure and other therapies using drugs glycyrrhizin, adrenocorticosteroids, interferon and the like. However, we cannot say that this therapy is quite effective for the treatment of tabachnogo introduction. In addition, interferon and steroids have problems associated with their side effects.

Some triterpene derivatives have anticomplement activity and activity to suppress platelet aggregation. Thus, they and the pharmaceutical compositions containing them, known as preventive and medicines against immunological diseases and thrombosis (Japanese Patent Laid-Open N 85344/1986). However, there is no message that describes what triterpene derivatives are effective in the form of pharmaceutical compositions for the treatment of liver diseases.

SUMMARY OF INVENTION

I found that some of triterpene derivative effective in the treatment of liver diseases. In addition, succeeded in synthesizing a new triterpene derivatives. This invention is based on these new data.

The first aspect of the present invention is a pharmaceutical composition for treating liver disease, comprising as an active ingredient triterpene derivative represented by the following formula (I) or its salt:

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where R1represents a hydroxyl group, kilmetros lower al where R5represents a hydrogen atom, arylmethyl, lower alkyl or lower alkanoyl,

formyl,

-COOR6where R6represents a hydrogen atom or lower alkyl, or

-CH2N(R7R8where R7and R8that may be the same or different, represent a hydrogen atom, lower alkyl, aryl or lower alkanoyl;

or R1and R2can be connected to each other to form-O-C(R9R10-O-CH2- where R9and R10that may be the same or different, represent a hydrogen atom, lower alkyl or aryl;

R3and R4that may be the same or different, represent a hydrogen atom, hydroxyl group, lower alkyl, lower alkenyl, aryl, hydroxymethyl,

-N(R11R12where R11and R12that may be the same or different, represent a hydrogen atom, lower alkyl or lower alkanoyl,

formyl,

-COOR6where R6defined above,

-OR13where R13represents lower alkyl, lower cycloalkyl, aralkyl, lower alkanoyl, arylcarbamoyl, aralkylamines, lower alkenyl, lower alkenylboronic or aryl-lower alkenylboronic;

or R3to place an O, CH2or NH.

The second aspect of the present invention is a pharmaceutical composition for treating liver disease, comprising as an active ingredient triterpene derivative represented by the following formula (II) or its salt:

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where R16represents a hydroxyl group, kilmetros, lower alkoxy or lower alkanoyloxy;

R17represents lower alkyl, lower alkenyl,

-CH2OR5where R5defined above,

formyl,

-COOR6where R6defined above,

-CH2OCON(R9R10where R9and R10defined above,

-CON(R29R30where R29and R30that may be the same or different, represent a hydrogen atom, lower alkyl, lower alkanoyl, aryl, or aralkyl;

-CH2N(R7R8where R7and R8defined above;

-C(R6)2OH, where R6defined above;

-COR6where R6defined above;

-CH=CHR6where R6defined above;

or R16and R17can be combined with each other to form-O-C(R9R10-O-CH2- where R9and R10defined above;

R18and R19, koishi alkyl,

-N(R11R12where R11and R12defined above,

-COOR6where R6defined above,

-OR13where R13defined above,

-O-(CH2)m-R22where R22represents amino,

-NH-COOR23where R23is arylmethyl or lower alkyl, a hydroxyl group, kilmetros or

-COOR24where R24represents a hydrogen atom, lower alkyl or arylmethyl and

m is an integer from 1 to 4

-OCOCH(R25) (CH2)n-R22where R22defined above, R25represents a hydrogen atom, lower alkyl, aralkyl or aryl, and n is an integer from 0 to 3,

-OCOCH=CH-COOR6where R6defined above, or

-OCON(R29R30where R29and R30defined above;

or R18and R19can be connected to each other to form oxo,

R20and R21, respectively, have the same meaning as R18and R19provided that R20and R21not represented by a hydrogen atom;

or R18and R20can be connected to each other to form-O-[C(R9R10]p-O-, where R9and R10defined above, and p is an integer from 1 to 3, or-OCO-[C(R9R10]single bond for the formation of a double bond in the ring, to which Y is attached.

The third aspect of the present invention is a pharmaceutical composition for treating liver disease, comprising as an active ingredient triterpene derivative having the formula (III) or its salt:

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where R1, R2and Y have the same meanings as above, and R27is

-O-(CH2)m-R22where R22and m have the same meanings as above,

-OCOCH(R25)(CH2)n-R22where R22, R25and n have the same meanings as above,

-OCON(R29R30where R29and R30have the same values as above,

-OCO-(CH2)n-R16where R16defined above, or

-OCOCH=CH-COOR6where R6defined above.

The fourth aspect of the present invention is a pharmaceutical composition for treating liver disease, comprising as an active ingredient triterpene derivative represented by the following formula (IV) or its salt:

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where R1, R18, R19and Y are defined above; and R28is

-CON(R29R30where R29and R30defined above,

-C(R6)2OH, where R6defined above,

-COR6awhere R
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where R1represents a hydroxyl group, lower alkoxy or lower alkanoyloxy;

R2represents hydroxymethyl, lower alkoxymethyl, lower alkanoyloxy or carboxyl;

or R1and R2can be combined with each other to form-O-C(R14R15-O-CH2- where R14and R15that may be the same or different, represent a hydrogen atom or lower alkyl;

R3and R4that may be the same or different, represent a hydrogen atom, hydroxyl group, lower alkyl, lower alkenyl, aryl, hydroxymethyl,

-N(R11R12where R11and R12that may be the same or different, represent a hydrogen atom, lower alkyl or lower alkanoyl,

formyl, -COOR6where R6defined above,

-OR13where R13represents lower alkyl, lower cycloalkyl, aralkyl, lower alkanoyl, arylcarbamoyl, aralkylamines, lower alkenyl, lower alkenylboronic or aryl-lower alkenylboronic;

or R3and R4can be connected to each other to form oxo, hydroxyimino or alkylidene; and

X Prescr>2represents hydroxymethyl, R3represents a hydrogen atom, R4represents a hydroxyl group, and X represents O, are excluded.

The second group of new compounds of this invention are triterpene derivatives represented by the following formula (IIa) or their salts:

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where R16represents a hydroxyl group, kilmetros, lower alkoxy, excluding methoxy, or lower alkanoyloxy, excluding acetoxy;

R17represents lower alkyl, lower alkenyl,

-CH2OR5where R5defined above, formyl,

-COOR6where R6defined above,

-CH2OCON(R9R10where R9and R10defined above,

-CON(R7R8where R7and R8defined above,

-CH2N(R7R8where R7and R8defined above,

-C(R6)2OH, where R6defined above,

-COR6awhere R6arepresents lower alkyl, or

-CH=CHR6where R6defined above,

or R16and R17can be connected to each other to form-O-C(R9R10-O-CH2- where R9and R10defined above,

R18and R19that can be R11R12where R11and R12defined above,

-COOR6where R6defined above,

-OR13where R13defined above,

-O-(CH2)m-R22,

where R22represents amino,

-NH-COOR23where R23is arylmethyl or lower alkyl,

hydroxyl group, kilmetros or

-COOR24where R24represents a hydrogen atom, lower alkyl or arylmethyl and

m is an integer from 1 to 4

-OCOCH(R25)(CH2)n-R22where R22defined above,

R25represents a hydrogen atom, lower alkyl, aralkyl or aryl and n is an integer from 0 to 3,

-OCOCH=CH-COOR6where R6defined above, or

-OCON(R29R30where R29and R30defined above;

or R18and R19can be combined with each other to form oxo,

R20and R21, respectively, have the same meaning as R18and R19provided that R20and R21are not a hydrogen atom;

or R18and R20can be connected to each other to form-O-[C(R9R10] p-O-, where R9and R10shall have the same meaning as above, and p is an integer from 1 to 3, /BR> Y represents O, CH2, NH or a single bond with formation of a double bond in the ring to which Y is attached; provided that the compounds wherein R16represents a hydroxyl group, R17represents-CH2OCH3, R20represents a hydroxyl group or methoxy, both, R18and R21represent hydrogen atoms, R19represents a hydroxyl group or methoxy, and Y represents a single bond, and compounds in which R16represents a hydroxyl group, R17is CH2OH, R20represents a hydroxyl group, R18, R19and R21, R20represents a hydroxyl group, R18, R19and R21represent a hydrogen atom, and Y represents a single bond, is excluded.

The third group of new compounds of this invention are compounds represented by the formula (III).

The fourth group of new compounds of this invention are compounds represented by the formula (IV).

In the drawing given graph showing the effect of pharmaceutical compositions for the treatment of liver diseases according to this invention, when the hepatitis caused by concanavalin And mice. And the screens 2068518(u/l) for the control group, whereas for the group of mice that were treated with a pharmaceutical composition for the treatment of liver disease according to this invention, it falls to 5516 (IU/l) level, which was the same as in the group not exposed (i.e., normal values).

A DETAILED DESCRIPTION OF THE INVENTION

Definition

The term "lower alkyl", used herein as a group or part of a group, indicates the lowest alkali straight or branched chain, which preferably have from 1 to 6 carbon atoms, more preferably from 1 to 4 carbon atoms. The terms "lower alkenyl" and "lower quinil" as a group or part of a group, represent the lowest of alkenyl or lower alkinyl straight or branched chain, which preferably have from 2 to 6 carbon atoms, more preferably from 2 to 4 carbon atoms.

The term "halogen atom" means a fluorine atom, chlorine, bromine or iodine. The term "aryl" preferably means phenyl, naphthyl, tolyl, methoxyphenyl or the like. The term "aralkyl" as a group or part of a group, preferably means phenyl-Cl4-alkyl, more preferably benzyl, phenethyl or the like.

In the compounds of the present invention examples Ari is a straight or branched chain, having from 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tributoxy, pentyloxy, hexyloxy.

Examples of lower alkanoyloxy include alkanoyloxy with a straight chain having from 2 to 6 carbon atoms, such as acetoxy, propionyloxy, butyryloxy, pentanoate, hexanoate.

Examples of lower alkanoyl include alkanoyl straight or branched chain, having from 1 to 6 carbon atoms, such as formyl, acetyl, propionyl, butyryl, isobutyl, pentanoyl, tert-butylcarbamoyl and hexanoyl.

Examples of lower alkyl include alkali straight or branched chain, having from 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl and hexyl.

Examples of lower alkenyl include alkenyl straight or branched chain, having from 2 to 6 carbon atoms, such as vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl and 2-hexenyl.

Examples of aryl include phenyl, naphthyl and biphenyl.

Examples of the lower cycloalkyl include cyclopropyl, cyclopentyl and cyclohexyl. Examples of aralkyl include benzyl, phenethyl and phenylpropyl.

Examples of arylcarbamoyl include benzoyl and n is s carbon such as acryloyl, arylcarbamoyl and 2-butylcarbamoyl.

Examples of aralkylamines include phenylacetyl, phenylpropionyl and naphthylacetyl. Examples of arancelaria include cynnamoyl and phenylethanol.

Examples of alkylidene include ethylidene, propeller and butylidene.

As for kilmetros, aryl, aralkyl, arylcarbamoyl, aralkylamines and arancelaria at least one hydrogen atom may be substituted by a number of substituents, preferably 1 to 2, and examples of the substituents include methyl, ethyl, methoxy, ethoxy, halogen atom, amino, dimethylamino, hydroxyl group, acetoxy, methylendioxy.

Pharmaceutical composition for the treatment of liver diseases/the compounds of formula (I), (II), (III) and (IV)

Compounds represented by the General formula (I), (II), (III) or (IV), and their salts are effective in the treatment of liver diseases.

Liver disease, in which there may be used compounds represented by the General formula (I), (II), (III) or (IV) and their salts include acute and chronic viral hepatitis, autoimmune hepatitis caused by drugs, toxic, alcoholic, intrahepatic cholestasis and hepatopathy due to congenital disorders is depending on the development of symptoms is used as a concept covering well as fatty infiltration of the liver, cirrhosis and hepatoma.

Specifically, triterpene derivatives represented by the formula (I), (II), (III) or (IV), and their salts during incubation with cells human hepatoma (Hep G2) in the presence of aflatoxin B1 (the substance causing hepatopathy), possess suppressive activity against necrosis of these cells and suppressive activity against liver diseases with viral hepatitis in mice caused by concanavalin A.

Compounds represented by formula (I), (II), (III) or (IV) have different isomers and the invention includes these isomers and their mixtures. In addition, also consider the presence of isomers associated with other groups in the formula (I), (II), (III) or (IV), and these isomers and their mixtures are also included in this invention.

In accordance with a preferred embodiment of the present invention preferred compounds represented by formula (I), (II), (III) or (IV) have a configuration represented by the following formula (I-1), (II-1), (III-1) or (IV-1):

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Among the compounds represented by formula (I), (II), (III) or (IV) according to this invention, the following preferred groups of compounds.

Thu is that R1represents a hydroxyl group, R3represents a hydrogen atom and X represents O; and a group of compounds, where R1represents a hydroxyl group, R2represents hydroxymethyl, R3represents a hydrogen atom, R4represents a hydroxyl group or-OR13, a X is O.

As for the compounds represented by formula (II), preferred are:

a group of compounds, where R16represents a hydroxyl group, R17represents-CH2OH, both, R18and R20represent a hydrogen atom, both, R19and R21represent a hydroxyl group, and Y represents a single bond with formation of a double bond in the ring to which Y is attached;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents - CH2OR5, R18represents a hydrogen atom, R19is-OR13, R20represents a hydrogen atom, R21is-OR13and Y represents a single bond with formation of a double bond in the ring to which Y is attached;

a group of compounds, where R16represents a hydroxyl group,shall apply to each other to form oxo, R20and R21are connected to each other to form oxo and Y represents a single bond with formation of a double bond in the ring to which Y is attached;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents - CH2OR5, R18and R19are connected to each other to form oxo, R20represents a hydrogen atom, R21represents a hydroxyl group, and Y represents a single bond with formation of a double bond in the ring to which Y is attached;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents - CH2OR5, R18and R19represents a hydrogen atom, R20and R21are connected to each other to form oxo and Y represents a single bond with formation of a double bond in the ring to which Y is attached;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy, excluding methoxy, or lower alkanoyloxy, excluding acetoxy, R17represents-CH7OR5, R18and R19represent a hydrogen atom, R20the submitted the double bond in the ring, to which Y is attached;

a group of compounds, where R16represents a hydroxyl group, R17represents-CH2OR5, R18represents a hydrogen atom, R19represents a hydroxyl group or-OR13, R20represents a hydrogen atom, R21represents a hydroxyl group or-OR13and Y represents a single bond and, thus, represents O;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents-C(R6)2OH, R18represents a hydrogen atom, R19represents a hydroxyl group or-OR13, R20represents a hydrogen atom, R21represents a hydroxyl group or-OR13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17is-COR6a, R18represents a hydrogen atom, R19represents a hydroxyl group or or13, R20represents a hydrogen atom, R21represents a hydroxyl group or-OR13a Y presti, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents-CH=CHR6, R18represents a hydrogen atom, R19represents a hydroxyl group or-OR13, R20represents a hydrogen atom, R21represents a hydroxyl group or-OR13, Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

For compounds represented by formula (III), preferred are:

a group of compounds, where R1represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R2represents - CH2OR5, R27represents-OCO-(CH2)n-R16and Y represents a single bond for the formation of a double bond in the ring to which Y is attached;

a group of compounds, where R1represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R2represents-CH2OR5, R27represents-O-(CH2)m-R22and Y represents a single bond for the formation of a double bond in the ring to which Y is attached;

a group of compounds, where R1represents a hydroxyl group, lower alkoxy or lower and>or-OCOCH= CH-COOR6, Y represents a single bond for the formation of a double bond in the ring to which Y is attached;

a group of compounds, where R1represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R2represents - CH2OR5, R27is-OCON(R29R30and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

For compounds represented by formula (IV), preferred are:

a group of compounds, where R18and R19represent a hydrogen atom, a hydroxyl group or-OR13, R28represents CON(R29R30where R29and R30defined above, -C(R6)2OH, where R6given the above definition, -COR6awhere R6adefined above, or-CH=CHR6where R6given the definition above.

Compounds represented by formula (I), (II), (III) or (IV) according to this invention can be present in salt form. Salt can be obtained by a simple reaction of the above compounds with a pharmaceutically acceptable base in the usual way. In this case, can be used as the basis inorganic bases, t is at sodium, and organic bases, such as piperazine, morpholine, piperidine, ethylamine and trimethylamine.

Although the connection according to this invention can be introduced in the form of pure substances, preferably it can be administered as pharmaceutical compositions. Pharmaceutical compositions in the form of pharmaceutical compositions for the treatment of liver diseases, comprising as an active ingredient the compound or its salt according to this invention, it is possible to enter or oral or parenteral (e.g., by intravenous injection, intramuscular injection, subcutaneous administration, rectal injection or intradermal injection) to people or other animals.

Therefore, the pharmaceutical composition for the treatment of hepatic diseases according to this invention can be manufactured in the form of a preparation suitable for the particular route of administration. Namely, they can be made in the form of any of the following drugs: injectable, such as injectable for intravenous or intramuscular injection; oral preparation such as capsules, tablets, granules, powders, pills, thin plates or lozenges; preparation for rectal administration; suppositories fat basis; and su using the basics fillers, binders, moisturizing agents, loosening substances, surface-active substances, substances that increase slip, dispersing agents, buffer, preservative, increase the solubility of substances, antiseptic, improves the taste of substances, sleek substance, stabilizer and the like. Examples of the above additives are non-toxic and acceptable for products include milk sugar, fruit sugar, grape sugar, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, methyl cellulose, carboxymethyl cellulose or its salt, Arabian gum, polyethylene glycol, syrup, vaseline, glycerin, ethanol, propylene glycol, citric acid, sodium chloride, sodium silicate and sodium phosphate.

The dose of a compound represented by the formula (I) may vary depending on age, weight, condition of the patient or the severity of the disease. Mostly, however, it is in the range of from about 0.1 to 1000 mg, preferably from 1 to 100 mg per day for an adult, with 1 or twice a day. The introduction may be either oral or parenteral.

A group of new compounds/compounds of formula (Ia), (IIa), (formula (Ia), (IIa), (III) or (IV).

Preferred examples of each group in these formulas may be the same as described above for formulas (I), (II), (III) and (IV).

In the above definition of formula (IIa) in respect of R16methoxy excluded from lower alkoxy, and acetoxy excluded from the lower alkanoyloxy. In respect of the following groups, however, methoxy included in the lower alkali represented by R16and acetoxy included in the lower alkanoyloxy represented by R16. Namely, these groups of compounds are:

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents - CH2OR5, R18represents a hydrogen atom, R19is-OR13, R20represents a hydrogen atom, R21is-OR13, Y represents a single bond for the formation of a double bond in the ring to which Y is attached;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents - CH2OR5, R18and R19are connected to each other to form oxo, R20and R21are connected to each other with OBrien;

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents - CH2OR5, R18and R19are connected to each other to form oxo, R20represents a hydrogen atom, R21represents a hydroxyl group, and Y represents a single bond for the formation of a double bond in the ring to which Y is attached; and

a group of compounds, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy, R17represents-CH2OR5, R18and R19represent a hydrogen atom, R20and R21are connected to each other to form oxo, and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

For these new compounds, a preferred group of compounds represented by formulas (I), (II), (III) and (IV), and the preferred configuration may be the same as described above for the above formula (I), (II), (III) and (IV).

Compounds represented by formulas (Ia), (IIa), (III) or (IV), also have various isomers, published the invention includes all such isomers and mixtures thereof. In addition, rassmatrie included in this invention. These compounds represented by formulas (Ia), (IIa), (III) and (IV), can also be easily converted into the corresponding salt, allowing pharmaceutically acceptable base to interact with these compounds. Preferred bases may be the same as described above for formulas (I), (II), (III) and (IV).

Obtaining compounds

Method (A)

Among the compounds represented by formula (I), the compound represented by formula (VI), where R1, R2, R3and R4defined above, can be obtained by reaction of the compound represented by the following formula (V), where R1, R2, R3, R4defined above, with an appropriate oxidizing agent.

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The solvents used in this reaction include, for example, dichloromethane, chloroform, benzene and toluene. Oxidizing agents that are acceptable here include, for example, perventing acid, m-chloroperbenzoic acid and peracetic acid, mainly oxidizing agent is used a quantity of 1 to 3 equivalents based on the amount of compounds represented by formula (V). The reaction may usually be carried out at a temperature of 0-60oC.

Method (B)

Among the triterpene derivatives, performance>defined above, can be obtained by reaction of the compound represented by the following formula (V), with cyclopropanation agent.

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The solvent used here include benzene, toluene, hexane, diethyl ether, tetrahydrofuran and 1,2-dichloroethane. Cyclopropylamine agents used herein include Z(Cu)-CH2I2and Et2Zn-CH2I2. Basically cyclopropenone agent is used in an amount of from 1 to 10 equivalents based on the amount of the substance represented by formula (V). The reaction may usually be carried out at a temperature of from 40 to 60oC. Adding to the system a Lewis acid such as titanium tetrachloride, often accelerates the reaction.

Method ()

Among the compounds represented by formula (I), the compound represented by formula (VIII), where R1, R2, R3and R4defined above, can be obtained by reaction of the compound represented by formula (V), IN3and then with the appropriate regenerating agent.

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Mainly IN3is used in an amount of from 1 to 3 equivalents based on the amount of the substance represented by formula (V). The solvents used in this reaction include DMF and Aino to use lithium alumoweld in an amount of from 1 to 5 equivalents, as the solvent used in this reaction with reducing agents include diethyl: ether and tetrahydrofuran, the Reaction with regenerating agent can be carried out at temperatures from 0 to 60oC.

Method (G)

Among the compounds represented by formula (II), the compound represented by formula (X), where R18, R19, R20and R21defined above, can be obtained by reaction of the compound represented by the following formula (IX), where R18, R19, R20and R21defined above, with an appropriate oxidizing agent.

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The solvents used in this reaction include, for example, dichloromethane, chloroform, benzene and toluene. Oxidizing agents used in this reaction include, for example, perventing acid, m-chloroperbenzoic acid and peracetic acid. Basically, the oxidizing agent is used in an amount of from 1 to 3 equivalents based on the amount of the compounds represented by formula (V). The reaction may usually be carried out at temperatures from 0 to 60oC.

Method (D)

Among the compounds represented by formula (III), the compound represented by formula (XIV) where R27*represents-O- (CH2)m-R22UP>, R22, R25, R29, R30n and m defined above, can be obtained using the following reaction.

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First, the compound represented by formula (XI), where R9and R10defined above, is reacted with a compound represented by the formula-Z-(CH2)m-R22where Z represents a halogen atom, Cl-CO-(CH2)n-R6or Cl-COCH=CH-COOR6in the presence or in the absence of grounds to obtain compounds represented by the formula (XIII) where R9, R10, R27*and m are defined above. Solvents used include diethyl ether, tetrahydrofuran, benzene, toluene, dichloromethane, chloroform, dimethylformamide. The base used include, for example, triethylamine, pyridine, 4-dimethylaminopyridine, sodium hydride, potassium hydride, n-utility, NaCH2SOCH3and tert-GFCF. The compound represented by the formula-Z-(CH2)m-R22where Z represents a halogen atom, ClCOCH(R25)(CH2) n-R22; R29-NCO, Cl-CO-(CH2)n-R16or Cl-COCH== CH-COOR6can be used in an amount of from 1 to 3 equivalents based on the amount of compounds represented by formula (IX).

The base may generally be used in colchest, can be used as solvent. The reaction may be conducted at temperatures from -60o60oC. the Base may generally be used in amounts of from 1 to 10 equivalents based on the amount of compounds represented by formula (XI), and in some cases, can be used as solvent. The reaction can be conducted at a temperature in the range from -20 to 60oC.

The compound represented by the formula (XIII), can be subjected to hydrolysis in the presence of acid to obtain a compound represented by the formula (XIV). Solvents used include methanol, ethanol, propanol, water, dichloromethane and chloroform. Acids used include mineral acids such as hydrochloric acid and sulfuric acid and a Lewis acid such as BF3Et2A. basically, the reaction can be conducted at temperatures from 0 to 120oC.

Method (E)

Among the compounds represented by formula (IV), the compound represented by formula (XVIII) can be obtained using the following methods.

< / BR>
First, the compound represented by the formula (XV), where Ar represents aryl, reacts with the compound represented by formula (XVI), where RNe, represented by the formula (XVII), where Ar, R29and R30defined above. Solvents used include, for example, dichloromethane, chloroform, benzene, toluene, tetrahydrofuran and dimethylformamide. Condensing agents used include, dicyclohexylcarbodiimide (DCC), DC-hydroxybenzotriazole, benzotriazol-1-yloxytris (dimethylamino)-phosphonium hexaflurophosphate (BOP reagent) and diphenylphosphoryl. The condensing agent may be used in amounts of from 1 to 3 equivalents based on the amount of the compound represented by the formula (XV). Usually, the reaction can be conducted at temperatures from -20 to 60oC.

The compound represented by formula (XVII) may be catalytically restored in the presence of a catalyst to obtain the compound represented by formula (XVIII). Solvents used include, for example, water, methanol, ethanol, tetrahydrofuran, dioxane, dichloromethane and chloroform. Catalysts used include, for example, Pd-C, Pd(OH)2-C. the Catalyst may be used in quantities of from 0.1 to 0.6 equivalent in calculating the amount of a substance represented by the formula (XVII).

Usually, the reaction can be carried out with the program, represented by the formula (XVII) can be further modified to obtain compounds represented by formula (IV).

The compound represented by the formula (XV) can be obtained using the following methods.

< / BR>
The compound represented by the formula (XVa), can react with the compound represented by the formula (XVb), in the presence of base, followed by removal of the protecting trialling group in a compound represented by the formula (XVc), where Ar represents an aryl group. Solvents used include diethyl ether, THF, DMF), dimethylsulfoxide (DMSO), benzene, and toluene. The base used include, for example, sodium hydride, potassium hydride, n-utility, NaCH2SOCH3and tert-GFCF. Preferably, the base and the compound represented by the formula (XVb), are used in quantities of from 1 to 10 equivalents based on the amount of the compound represented by the formula (XVa). Preferably, the reaction is carried out at a temperature of from -78 to 60oC. Removal of protection can be carried out in the presence of a mineral acid, such as hydrochloric acid or sulfuric acid, in a solvent such as methanol, ethanol, isopropyl alcohol (IPA) or water is by using the appropriate oxidizing substances with obtaining connection represented by formula (XVd). Oxidizing agents used include, for example, pyridinium chromate, pyridinium dichromate, manganese dioxide and DMSO oxidizing reagents, such as DMSO-oxalicacid. The solvents used in this reaction include dichloromethane, chloroform, diethyl ether and THF. Preferably, the oxidizing agent is used in an amount of from 1 to 5 equivalents based on the amount of compounds represented by formula (XVc), the Reaction can usually be carried out at a temperature of from -78 to 40oC.

The compound represented by formula (XVd), we can further oxidize with the appropriate oxidizing agent to obtain the compound represented by the formula (XV), the Solvents used include, for example, DMF, tert-butanol, acetone and water. Oxidizing agents used include pyridinium dichromate, Jones reagent, potassium permanganate and sodium chlorite. The oxidizing agent may be used in amounts of from 1 to 30 equivalents based on the amount of compounds represented by formula (XVd). The reaction may be conducted at temperatures from 0 to 60oC.

Way (W)

The compound represented by formula (I), where R1predstavljaet lower alkyl or lower alkanoyl), the compound represented by formula II, where R16is kilmetros, lower alkoxy or lower alkanoyloxy, and R17represents-CH2OR5(where R5represents lower alkyl or lower alkanoyl) and the compound represented by formula (III), where R1represents lower alkoxy or lower alkanoyloxy, a R2represents - CH2OR5(where R5represents lower alkyl or lower alkanoyl), can be obtained by the reaction of, respectively, the compounds represented by formula (I), where R1represents a hydroxyl group, and R2represents-CH2OH, the compounds represented by formula (II), where R16represents a hydroxyl group, and R17represents-CH2OH, and compounds represented by formula (III), where R1represents a hydroxyl group, a R2represents-CH2OH, with a compound represented by the formula, R5Z or R5a)2O, where R5arepresents lower alkyl or lower alkanoyl, in the presence of a base. The solvents used in this reaction include diethyl ether, tetrahydrofuran, benzene, toluene, dichloromethane, chloroform and dimethylformamide. The base used in the formula, R5Z or R5a)2O, is used in an amount of from 1 to 3 equivalents based on the amount of compounds represented by formulas (I), (II) and (III). The base is used in amounts of, preferably, from 1 to 10 equivalents based on the amount of compounds represented by formulas (I), (II) and (III), and in some cases, can be used as solvent. The reaction may be conducted at a temperature of from -20oC to 60oC.

Method (3)

Among the compounds represented by formula (II), the compound represented by the formula (XIX), where R*is-OR13, -O-(CH2)m-R22, -OCOCH(R25)(CH2)n-R22, -OCOCH=CH-COOR6or-OCON(R29R30can be obtained using the following reaction.

< / BR>
First, the compound represented by formula (XX) may react with the compound represented by the formula, R13Z, where Z represents a halogen atom, (R13)2O, Cl-COCH (R25)(CH2)n-R22, ClCOCH=CH-COOR6or R29-NCO in the presence of a base to obtain the compound represented by the formula (XIX). The solvents used in this reaction include, for example, diethyl ether, tetrahydrofuran, benzene, toluene, dichloromethane, chemiluminometer. The compound represented by formula 13Z, where Z represents a halogen atom, (R13)2O, Cl-COCH(R25)(CH2)n-R22, R29-NCO, Cl-CO-(CH2)n-R16or ClCOCH= CH-COOR6used in an amount of from 1 to 3 equivalents, based on the amount of compounds represented by formula (XX). Usually the base is used in an amount of from 1 to 10 equivalents based on the amount of compounds represented by formula (XX), and in some cases, as solvent. The reaction can be conducted at a temperature of from -60 to 60oC.

Among the compounds represented by formula (II), the compound represented by the formula (XIX), where R*is-OR13or-O-(CH2)m-R22can be obtained by reaction of the compound represented by formula (II), where R18represents a hydrogen atom, R19represents a hydroxyl group, R20represents a hydrogen atom and R21represents a hydroxyl group, with a compound represented by the formula, R13Z or Z-(CH2)m-R22where Z represents a halogen atom, in the presence of a base. Solvents used include, for example, diethyl ether, THF, benzene, toluene, DMF and DMSO. The base used. predpochtitelno, the base and the connection represented by R13Z or Z-(CH2)m-R22used in an amount of from 1 to 10 equivalents, based on the amount of compounds represented by formula (II). Preferably, the reaction is carried out at a temperature of from -78 to 60oC.

Method (S)

The compound represented by formula (I), where R3and R4are connected to each other to form oxo, the compound represented by formula (II), where R18and R19are connected to each other to form oxo, and/or R20and R21are connected to each other to form oxo, and the compound represented by formula (IV), where R18and R19are connected to each other to form oxo, can be obtained, respectively, by oxidation of the compounds represented by formula (I), where R3represents a hydrogen atom and R4represents a hydroxyl group, compounds represented by formula (II), where R18and R20represent a hydrogen atom, and both, R19and R21represent a hydroxyl group, or any one of R19and R21represents a hydroxyl group, and the other Deputy represents a hydrogen atom, and compounds predstavlennoj is using an oxidizing agent. Oxidizing agents used include, for example, chromate pyridinium, pyridinium dichromate, manganese dioxide and DMSO oxidizing agents, such as DMSO-oxalicacid. The solvents used in this reaction include dichloromethane, chloroform, diatrofi ether and THF. Preferably, the oxidizing agent is used in an amount of from 1 to 5 equivalents. The reaction may usually be carried out at a temperature of from -78 to 40o.

The way (TO)

The compound represented by formula (I), where R3represents a hydrogen atom, and R4represents a hydroxyl group, the compound represented by formula (II), where R18and R20represent a hydrogen atom, and as R19and R21represents a hydroxyl group, or any of the R19and R21represents a hydroxyl group, and the other Deputy represents a hydrogen atom, and the compound represented by formula (IV), where R18represents a hydrogen atom and R19represents a hydroxyl group can be obtained, respectively, by reduction of compound represented by formula (I), where R3and R4are connected to each other to form oxo, compounds represented by formula (II), where Re R18and R19are connected to each other to form oxo, using a reducing agent. Reducing agents used include, for example, lithium-alumoweld and sodium-borohydride. Usually reducing agent can be used in an amount of from 1 to 5 equivalents. Solvents used include, for example, diethyl ether, THF, benzene, toluene and dichloromethane. The reaction can be conducted at a temperature of from -78 to 60o.

Method (L)

Among the compounds represented by formula (II), the compound represented by formula (XXI) can be obtained using the following methods.

< / BR>
First, the compound represented by the formula (XXII) may react with the compound represented by the formula WSO2Cl, where W represents alkyl or aryl, in the presence of a base to obtain the compound represented by the formula (XXIII). Solvents used include benzene, toluene, dichloromethane, chloroform, diethyl ether, THF and DMF, Specific examples of compounds represented by formula WSO2Cl, include, for example, methanesulfonate, benzosulphochloride and p-toluensulfonate. The base used include n, the base is used in an amount of from 1 to 3 equivalents based on the amount of the compound represented by the formula (XXII). The reaction can be usually carried out at temperatures from 0 to 60o.

The compound represented by the formula (XXIII) may react with a regenerating agent to obtain the compound represented by formula (XXI). The solvents used in this reaction include, for example, diethyl ether, THF, benzene, toluene and dichloromethane. Reducing agents used include, for example, triethylborane-lithium hydride, and can generally be used in amounts of from 1 to 5 equivalents. The reaction can be conducted at a temperature of from -78 to 60o.

Method (M)

The compound represented by formula (IV), where R28represents-C(R6)2OH, can be obtained by reaction of the compound represented by formula (IV), where R28represents-CHO, with the compound represented by formula (R6)iMZjwhere R6defined above, M represents lithium, magnesium, zinc or aluminum, Z represents a halogen atom, i is an integer from 1 to 3, and j is 0 or 1. The solvents used in this reaction include diethyl ether, THF, benzene, t is raised by the formula (R6)iMZjused in an amount of from 1 to 3 equivalents based on the amount of compounds represented by formula (IV). Usually, the reaction can be conducted at a temperature of from -78 to 20o.

Way (N)

The compound represented by formula (IV), where R28represents-CH=CHR6can be obtained by reaction of the compound represented by formula (IV), where R28represents-CHO, refinerywill reagent. Solvents used include dichloromethane, chloroform, diethyl ether, THF, DMF and DMSO. Refinerys reagents used include, for example, Ph3P=CHK6the reagent Tebbe and reagent Nested. Preferably, refinery reagent is used in an amount of from 1 to 10 equivalents based on the amount of compounds represented by formula (IV). Usually, the reaction can be conducted at a temperature of from -78 to 40o. Adding a Lewis acid such as titanium tetrachloride, to the reaction system often accelerates the reaction and, hence, preferable.

The way (ABOUT)

The compound represented by formula (IV), where R28is-COR6or-C(R6)OH, can be obtained by reaction of the compounds represented by FD is where R6defined above, M represents lithium, magnesium, zinc or aluminum, Z represents a halogen atom, i is an integer scrap from 1 to 3, and j is 0 or 1. The solvents used in this reaction include diethyl ether, THF, benzene, toluene, hexane, dimethylformamide (DMF), hexamethylphosphoramide and dichloromethane. Preferably, the compound represented by formula (R6)iMZjused in an amount of from 1 to 3 equivalents based on the compound represented by formula (IV). Usually, the reaction can be conducted at a temperature of from -78 to 20oC.

The specialist should be clear that a variety of compounds represented by formulas (I), (II), (III) and (IV) can be obtained by using a combination of the above methods (A) to (M). In addition, in the above methods, the obvious possibility of pre-introduction of protective groups which do not participate in the reaction or inert in respect of the inclusion in the reaction. In this regard, the use of commonly used protective groups also obvious to the specialist.

EXAMPLES

The invention will be described in more detail with reference to the following examples, although it is not limited to only these examples.

the bath by a joint generalization of structures, respectively represented by formulas (I), (II), (III) and (VI).

Compounds 3, 11, 18 and 21 were obtained in accordance with the method described in Chem. Pharm. Bull. , 36, 153 (1988), and compounds 1 and 7 were obtained in accordance with the method described in Ber., 70, 2083, 2093 (1937), Ber. , 71, 790, 1604 (1938), Chem. Pharm. Bull., 31, 664 (1983) and Chem, Pharm. Bull., 31, 674 (1983).

Example 1

12 , 13 - Epoxyoctane-3 , 22 , 24 (4)- triol (compound 2)

Connection 1 (230 mg, 0.5 mmol) was dissolved in 10 ml dichloromethane and 3 ml of chloroform, the solution was added 216 mg 50-60% m-chloroperoxybenzoic acid, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate and then with saturated salt solution and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain oil, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 1:1) to give 193 mg (yield 81%) of compound 2 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.88 (3H, s), 0.90 (3H, s), 0.97 (3H, s), 0.98 (3H, s), 0.99 (3H, s), 1.04 (3H, s), 1.22 (3H, s), 0.74-1.87 (22H, m), 2.36 (1H, d, J = 4.16 C]

MS EI (m/z): 474 (M+)

Example 2

3 , 24 (4), Isopropylidenedioxy-22 - metaxylem-12-EN

(compound 4)

Compound 3 (300 mg) was dissolved in 5 ml TF, to the solution were added 130 mg of 55% sodium hydride and the mixture was stirred at room temperature for 1 hour. Then added 2 ml under the conditions and the mixture was stirred over night. The reaction solution was diluted with ethyl acetate, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 10:1) to give 285 mg (yield: 93%) of compound 4 as a colorless foam.

1H-NMR (CDCl3) memorial plaques

0.86 (3H, s), 0.90 (3H, s), 0.99 (3H, s), 1.00 (3H, s), 1.11 (3H, s), 1.15 (3H, s), 1-22 (3H, s), 1.37 (3H, s), 1.44 (3H, s), 0.83-2.10 (21H, m), 2.80-2.83 (1H, m), 3.23 (1H, d, J = 11-8 Hz), 3.28 (3H, s), 3.44-3.47 (1H, m), 4.06 (1H, d, J = 11.8 Hz), 5.23 (1H, t-like)

t-like = t-like

MC FD (m/z): 512 (M+)

Example 3

22 - Metaxylem-12-ene-3 , 24 (4)- diol (compound 5)

Compound 4 (280 mg) was dissolved in THF, the solution was added to 0.66 ml nortryptaline ethyl ether and the mixture was stirred at room was temperaturestable with ethyl acetate. The extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 2: 1) to give 203 mg (yield: 79%) of compound 5 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.85 (3H, s), 0.89 (3H, s), 0.90 (3H, s), 0.94 (3H, s), 1.00 (3H, s), 1.11 (3H, s), 1,25 (3H, s), 0.80-2.10 (21H, m), 2.80-2.82 (1H, m), 3.28 (3H, s), 3.33 (1H, d, J = 11.1 Hz), 3.42-3.45 (1H, m), 5.22 (1H, t-like)

MC EI (m/z): 472 (M+)

Example 4

22 - Methoxy-12,13-epoxyresin-3 , 24 (4)- diol (compound 6)

Compound 5 (50 mg, 0.1 mmol) was dissolved in 1 ml dichloromethane, to the solution was added 31 mg, 70% m-chloroperoxybenzoic acid and the mixture was stirred at room temperature overnight. The reaction solution was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate and then with saturated salt solution and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain solid, which was purified by column chromatography on silica gel (developing systems="ptx2">

1H-NMR (CDCl3) memorial plaques

0.87 (3H, s), 0.89 (3H, s), is 0.96 (3H, s), 0.97 (3H, s), 0.99 (3H, s), 1.04 (3H, s), 1.22 (3H, s), 0.74-1.88 (21H, m), 2.42 (1H, br. s), 2.80 (1H, br. s), 2.94 (1H, dd, J = 3.33 Hz, 9.71 Hz), 3.04 (1H, s), 3.26 - 3.30 (1H, m), 3.29 (3H, s), 3.40-3.44 (1H, m), 4.17 (1H, d, J = 9.71 Hz)

MC EI (m/z): 488 (M+)

Example 5

12,13-Epoxyresin-3 , 21 , 22 , 24 (4)- tetraol (compound 8)

Compound 7 (50 mg, 0.1 mmol) was dissolved in 1 ml dichloromethane and 1 ml of chloroform, the solution was added 32 mg of 70% m-chloroperoxybenzoic acid and the mixture was stirred at a temperature of 37oC during the night. The reaction solution was diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate and then with saturated salt solution and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain solid, which was purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate =1:1) to give 18 mg (yield: 35%) of compound 8 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), of 0.91 (3H, s), 1.00 (3H, s), 1.05 (3H, 5), 1.13 (3H, s), 1.14 (3H, s), 1.23 (3H, s), 0.75-2.08 (23H, m), 3.03 (1H, s), 3.28 (1H, d, J = 11.28 Hz), 3.40-3.51 (3H, m), 4.17 (1H, d, J = 11.28 Hz)< / BR>
MC FAB (m/z): 491 (M++1)

Example 6

what if in 5 ml of dichloromethane, to the solution was added 15 mg of 4-dimethylaminopyridine and 18 μl of benzyloxyacetaldehyde and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 3:1) to give 36 mg (yield: 76%) of compound 9 as a colorless foam.

1H-NMR (CDCl3) memorial plaques

0.81 (3H, s), of 0.90 (3H, s), 0.96 (3H, s), 0.98 (3H, s), 1.14 (3H, s), 1.15 (3H, s), 1.22 (3H, s) to 1.38 (3H, s), 1.44 (3H, s), 0.87-2.20 (21H, m), 3.23 (1H, d, J = 11.65 Hz), 3.46 (1H, dd, J = 4.44 Hz, 11.44 Hz), 4.03-4.10 (3H, m), 4.64 (2H, d, J = 1.94 Hz), 4.78 (1H, t-like), 5.25 (1H, t-like), 7.30-7.39 (5H, m)

MC FAB (m/z): 647 (M++1)

Example 7

22 - -Benzyloxyacetaldehyde-12-ene-3 , 24 (4)- diol (compound 10)

Compound 9 (36 mg) was dissolved in 1 ml dichloromethane and 2 ml of methanol, to the solution was added 1 ml of hydrochloric acid and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and filego substances.

1H-NMR (CDCl3) memorial plaques

0.80 (3H, s), 0.89 (3H, s), 0.90 (3H, s), 0.94 (3H, s), is 0.96 (3H, s), 1.14 (3H, s), 1.25 (3H, s), 0.84-2.20 (21H, m), 3.35 (1H, d, J = 11.1 Hz), 3.42-3.47 (1H, m), 4.10 (2H, dd, J = 16.37 Hz, 26.91 Hz), 4.20 (1H, d, J = 11.1 Hz), with 4.64 (2H, d, J = 1.67 Hz), 4.78 (1H, t-like), 5.24 (1H, t-like), 7.28-7.38 (5H, m)

MC EI (m/z): 606 (M+)

Example 8

3 , 22 Dimensions-24 (4)- triphenyltetrazolium-12-ene (compound 12)

Compound 11 (95 mg) was dissolved in 5 ml of anhydrous DMF, the solution was added 83 mg of 60% sodium hydride and the mixture was stirred at room temperature for 1.5 hour. Then to the reaction mixture was added 75 μl of benzylbromide and the mixture was stirred at 40oC for 5 hours. The reaction mixture was diluted with ethyl acetate, washed three times with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain oil, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 10:1) to give 118 mg (yield:65%) of compound 12 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.33 (3H, s), 0.82 (3H, s), 0.88 (3H, s), 0.92 (3H, s), 1.03 (3H, s), 1.08 (3H, s), 1.34 (3H, s), 0.70-2.15 (21H, m), 2.93-2.97 (1H, m), 3.06-3.07 (1H, m), 3.17 (1H, d, J = 11.9 Hz), 3.53 (1H, d, J = 9.2 Hz), 4.32 (1H, d, J = 11.9 Hz), 4.38 (1H, d, J = 1 is benzisoxazole-12-EN-24 (4)- ol (compound 13)

Compound 12 (440 mg) was dissolved in 10 ml of methanol and 2 ml of acetone. To the solution was added concentrated hydrochloric acid (0.4 ml) and the mixture is boiled under reflux for 30 minutes To the reaction solution were added water and the mixture is then neutralized 1 N sodium hydroxide and was extracted three times with methylene chloride. The organic layer was dried over magnesium sulfate, inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain oil, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 10:1) to give 231 mg (yield: 72%) of compound 13 in the form of butter.

1H-NMR (CDCl3) memorial plaques

0.88 (3H, s), 0.89 (3H, s), 0.93 (3H, s), 0.94 (3H, s), 1.05 (3H, s), 1.11 (3H, s), 1.21 (3H, s), 0.85-2.18 (22H, m), 3.07-3.08 (1H, m), 3.18-3.24 (2H, m), 4.16 (1H, d, J = 10,5 Hz), 4,32 (1H, d, J = 11.7 Hz), 4.39 (1H, d, J = 11.7 Hz), 4.62 (1H, d, J = 11.7 Hz), 4.67 (1H, d, J = 11.7 Hz), 5.22 (1H, t-like), 7.26-7.34 (10H, m)

MC SIMS [SIMS] (m/z): 639 (M++1)

Example 10

3 , 22 Dimensions-24(4 )-oxolan-12-ene (compound 14)

Oxalicacid (0.15 ml) was dissolved in 4 ml of methylene chloride and the solution was cooled to -7oC. To the cooled solution was added a solution of 0.23 ml of DMSO in methylene chloride and the mixture was stirred for 10 minutes To obtained shivali at -78oC for 15 minutes To the reaction solution was added 0.7 ml of triethylamine and the mixture was stirred at -78oC for 5 minutes the temperature of the reaction solution was gradually raised to 0oC. the Reaction solution was diluted with water, extracted with methylene chloride, washed with saturated sodium bicarbonate and dried over anhydrous magnesium sulfate. Inorganic salt was removed by filtration, the filtrate was concentrated under reduced pressure and the resulting oil was purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 10: 1) to give 104 mg (yield: 82%) of compound 14 as a colorless foamy substance.

1H-NMR (CDCl3) memorial plaques

0.83 (3H, s), 0.89 (3H, s), 0.93 (3H, s), 0.94 (3H, s), 1.04 (3H, s), 1.10 (3H, s), 1.21 (3H, s), 0.85-2.18 (21H, m), 3.07 (1H, dd, J = 3.1 Hz, 3.1 Hz), 3.18 (1H, dd, J = 5.1 Hz, 5.1 Hz), 4,20, 4.61 (1H, each, both d, J = 11.7 Hz), 5.23 (1H, t-like), 7.22-7.35 (10H, m), 10.07 (1H, s)

MC SIMS [SIMS] (m/z): 637 (M++1)

Example 11

3 , 22-Dibenarkan-12-EN-24 (4)- OIC acid (compound 15)

Compound 14 (20 mg) was dissolved in 6 ml of tert-butanol are added and to this solution was added 1.5 ml of 2-methyl-2-butene. To the reaction solution was added a solution of 250 mg of sodium chlorite and 250 mg monolatry phosphate 2.5 ml of water and snejanna pressure and extracted with ethyl acetate, and the extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain oil, which was then purified by column chromatography on silica gel {manifest system, n-hexane: ethyl acetate =5:1) to give 6.8 mg {yield: 34%) of compound 15 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), 0.94 (3H, s), 0.95 (3H, s), 1.02 (3H, s), 1.04 (3H, s), 1.10 (3H, s), 1.40 (3H, s), 0.85-2.19 (21H, m), 3.05-3.09 (1H, m), 3.15-3.19 (1H, m), 4.32 (1H, d, J = 11-83 Hz), 4.56 (1H, d, J - 11.83 Hz), 4.61 (1H, d, J = 11-83 Hz), 4.85 (1H, d, J = 11.83 Hz), 5.23 (1H, t-like), 7.23-7.52 (10H, m).

MC EI (m/e): 652 (M+)

Example 12

Amide N-n-butyl-3 , 22 - dibenzalacetone-12-EN-24 (4)- OIC acid (compound 16)

Compound 15 (20 mg) was dissolved in 1 ml anhydrous DMF. To the solution was added BOP reagent (16 mg) and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added n-butylamine (0.1 ml) and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with ethyl acetate, washed twice with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate is tat =5:1) to give 16 mg (yield: 73%) of compound 16 as a colorless foam.

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), 0.92 (3H, s), 0.93 (3H, s), 1.01 (3H, s), 1.04 (3H, s), 1.10 (3H, s), 1.34 (3H, s), 0.82-2.25 (28H, m), 3.08 - 3.18 (4H, m), 4.32 (1H, d, J = 11.65 Hz), 4.46 (1H, d, J = 11.65 Hz), 4.61 (1H, d, J = 11.65 Hz), 4.75 (1H, d, J = 11.65 Hz), 5.23 (1H, t-like), 7.28 - 7.37 (10H, m), 7.50 (1H, t-like)

MC FAB (m/z): 708 (M++1)

Example 13

Amide N-n-butyl-3 , 22 - dihydroxytoluene-12-EN-24 (4)- OIC acid (compound 17)

Compound 16 (13 mg) was dissolved in 1 ml methanol and 1 ml of dichloromethane and to this solution was added 13 mg of 10% Pd-C. the Mixture was catalytically restored at room temperature under atmospheric pressure for 2 hours. The reaction solution was filtered through brownmillerite and the filtrate was concentrated under reduced pressure to obtain 10 mg (yield: 100%) of compound 17 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.87 (3H, s), 0.90 (3H, s) to 0.92 (3H, s), 1.02 (3H, s), 1.04 (3H, s), 1.12 (3H, s), 1.38 (3H, s), 0.91-2.22 (29H, m), 3.10-3.25 (3H, m),3.40 - 3.45 (1H, m), 3.77 (1H, d, J = 8.75 Hz), 5.27 (1H, t-like), 5.97 (1H, t-like)

MC EI (m/e): 527 (M+)

Example 14

3 , 24 (4), Diacetoxy-21 , 22 - isopropylidenedioxy-12-ene (compound 19)

21 , 22 - Isopropylidenedioxy-12-ene-3 , 24 (4)- diol (compound 18) (20 mg) was dissolved in 0.5 ml of anhydrous pyridine, the solution was added 0.5 ml of anhydrous acetic acid and the mixture is AC the Vali with ethyl acetate and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate =3:1) to give 19 mg (yield: 80%) of compound 19 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.92 (3H, s), 0.98 (9H, s), 1.00 (3H, s), 1.03 (3H, S), 1.11 (3H, s), 1.34 (3H, s), 1.49 (3H, s), 2.04 (3H, s), 2 07 (3H, s), 1.00-2.28 (19H, m), 3.73 (2H, s), 4,14 (1H, d, J= 11.5 Hz), 4.37 (1H, d, J = 11.5 Hz), 4.57-4.61 (1H, m), 5.27 (1H, t-like)

MC EI (m/z): 598 (M+)

Example 15

3 , 24 (4)- Gazeteciler 12-ene-21 , 22 - diol (compound 20)

Compound 19 (18 mg) was dissolved in 0.5 ml of dichloromethane and 1 ml of methanol, to the solution was added 0.2 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, dichloromethane: ethyl acetate =3:1) to give 14 mg (yield: 79%) of compound 20 as a colourless solid.


dd, J = 3.6 Hz, 7.5 Hz), 4.14 (1H, d, J = 11.7 Hz), 4.37 (1H, d, J = 11.7 Hz), 4.56-4.61 (1H, m), 5.26 (1H, t-like)

MC FAB (m/z): 581 (M+)

Example 16

3 , 24 (4)- Dimethoxytoluene-12-ene-21 , 22 - diol (compound 22)

21 , 22 Isopropylidenedioxy-3 , 24 (4)- dimethoxytoluene-12-ene (compound 21) (15 mg) was dissolved in 1 ml dichloromethane and 1 ml of methanol, to the solution was added 0.2 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 12 mg (yield: 87%) of compound 22 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.97 (6H, s), 0.99 (3H, s), 1.00 (3H, s), 1.02 (3H, s), 1.12 (3H, s), 1.14 (3H, s), 0.73-2.26 (21H, m), 2.72 (1H, dd, J = 4.2 Hz, 11.9 Hz), 3.27 (3H, s), 3.31 (1H, d, J = 9.7 Hz), 3.35 (3H, s), 3.41 (1H, t, J = 3.6 Hz), 3.51 (1H, dd, J = 3.6 Hz, 7.5 Hz), 3.54 (1H, d, J = 9.7 Hz), 5.27 (1H, t-like)

MC EI (m/z): 502 (M+)

Example 17

3 , 24 (4)- Benzylideneacetone-12-ene-21 , 22 - diol (compound 23)

Sousaphones A (compound 7) (1.0 g) was dissolved in 10 ml anhydrous DMF and to the solution was added to 0.38 ml of dimethylacetal benzaldehyde and 10 mg camphorsulfonate, and the mixture peremeshannnym solution of sodium bicarbonate and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate. - 2:1) to obtain 728 mg (yield: 61%) of compound 23 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.96 (6H, s), 0.97 (3H, s), 1.00 (3H, s), 1.02 (3H, s), 1.08 (3H, s), 1.17 (3H, s), 1.48 (3H, s), 0.90-2.47 (21H, m), 3.42 (1H, br s), 3.51 (1H, br s), 3.62 (1H, d, J = 11.0 Hz), 3.64 (1H, dd, J = 5.4 Hz, 12.1 Hz), 4.31 (1H, d, J = 11.0 Hz), 5.27 (1H, t-like), 5.78 (1H, s), 7.32-7.39 (3H, m), 7.49-7.52 (2H, m)

MC FAB (m/z): 585 (M+Na+)

Example 18

21 , 22 Diacetoxy-3 , 24 (4)- benzylideneacetone-12-ene (compound 24) and

21 - acetoxy-3 , 24 (4)- benzylideneacetone-12-EN-22 - ol (compound 24)

Compound 23 (100 mg) was dissolved in 2.5 ml of anhydrous pyridine, the solution was added 1 ml of anhydrous acetic acid and the mixture was stirred at room temperature for 3 hours. To the reaction solution was added ice water, extracted with ethyl acetate and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which is then purified of PHOTOMOD: 20%) of compound 24 and 69 mg (yield 65%) of compound 25 as colorless solids.

1H-NMR (CDCl3) M. D. (compound 24)

0.80 (3H, s), 0.88 (3H, s), 0.97 (3H, s), 1.07 (3H, s), 1.08 (3H, s), 1.18 (3H, s), 1.48 (3H, s), 2.00 (3H, s), 2 07 (3H, s), 0.89-2.47 (19H, m), 3.62 (1H, d, J = 11.0 Hz), 3.64 (1H, dd, J = 5.1 Hz, 12.1 Hz), 4.30 (1H, d, J = 11.0 Hz), 4.90 (2H, s), 5.29 (1H, t-like), 5.78 (1H, s), 7.30-7.39 (3H, m), 7.49-7.52 (2H, m)

MC EI (m/z): 647 (M+H)+< / BR>
1H-NMR (CDCl3) M. D. (compound 25)

0.87 (3H, s), 0.97 (3H, s), 1.00 (3H, s), 1.08 (3H, s), 1.13 (3H, s), of 1.18 (3H, s), 1.49 (3H, s), 2.14 (3H, s), 0.90-2.48 (20H, m), 3.46 (1H, d, J = 3.1 Hz), 3.62 (1H, d, J = 11.3 Hz), 3.65 (1H, dd, J = 5.9 Hz, 12.8 Hz), 4.31 (1H, d, J = 11.3 Hz), 4.94 (1H, d, J = 3,1 Hz), 5.28 (1H, t-like), 5.79 (1H, s), 7.28-7.39 (3H, m), 7.49-7,52 (2H, m)

MC EI (m/z): 604 (M+)

Example 19

21 , 22 - Gazeteciler-EN-3 , 24 (4)- diol (compound 26)

Compound 24 (23 mg) was dissolved in 1 ml methanol and 1 ml of dichloromethane and to the solution was added 5 mg of 10% Pd-C. the Mixture was catalytically restored at room temperature under atmospheric pressure for 4 hours. The reaction solution was filtered through brownmillerite and the filtrate was concentrated under reduced pressure to obtain 16 mg (yield: 82%) of compound 26 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.79 (3H, s), 0.87 (3H, s) to 0.89 (3H, s), 0.94 (3H, s), 1.07 (3H, s), 1.16 (3H, s), 1.25 (3H, s), 0.83-1.98 (18H, m), 2.00 (3H, s), 2.06 (3H, s), 2.23-2.28 (1H, m), 2,48 (1H, br s), 2.72 (1H, br s), 3.32-3.38 (1H, m), 3.45 (1H, dd, J = 5.4 Hz, 12.1 Hz), 4.20 (1H, d, J = 11.1 Hz), 4.89 (2H, sR>
Compound 25 (20 mg) was dissolved in 1 ml methanol and 1 ml of dichloromethane and to the solution was added 5 mg of 10% Pd-C. the Mixture was catalytically restored at room temperature under atmospheric pressure for 1 hour. The reaction solution was filtered through brownmillerite and the filtrate was concentrated under reduced pressure to obtain 13 mg (yield: 79oC) compound 27 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.85 (3H, s), 0.89 (3H, s), 0.96 (6H, s), 1.12 (3H, s), 1.15 (3H, s), 1.25 (3H, s), 0,84-1.98 (19H, m), 2.13 (3H, s), 2.28-2.34 (1H, m), 2.43 (1H, br s), 2.71 (1H, br s), 3.32-3.50 (3H, m), 4.21 (1H, d, J = 11.1 Hz), 4.93 (1H, d, J = 3.3 Hz), 5.26 (1H, t-like)

MC FAB (m/z): 539 (M+Na+)

Example 21

3 , 24 (4), Benzyladenine-21 , 22 - dimethoxytoluene-12-ene (compound 28),

3 , 24 (4), benzyladenine-22 - metaxylem-12-EN-21 - ol (compound 29) and

3 , 24 (4), benzyladenine-21 - metaxylem-12-EN-22 - ol (compound 30)

Compound 23 (20 mg) was dissolved in anhydrous THF, the solution was added 14 mg of 60% sodium hydride and the mixture was stirred at room temperature for 1 hour. Then to the reaction mixture were added 32 μl under the conditions and the mixture was stirred for 6 hours. To the reaction solution were added water and the mixture was extracted with ethyl acetate. The extract was dried in the tion to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 3:1) to give 6 mg (yield: 28%) of compound 28.5 mg (yield: 26%) of the compound 29 and 3 mg (yield; 14%) of compound 30 as a colorless solid substance.

1H-NMR (CDCl3) M. D. (compound 28)

0.94 (6H, s), 0.99 (3H, s), 1.03 (3H, s), 1.07 (3H, s), 1.15 (3H, s), 1.48 (3H, s), 0.88-2.47 (19H, m), 3.02 (2H, br s), 3.43 (3H, s), 3.46 (3H, s), 3.62 (1H, d, J = 11.5 Hz), 3.64 (1H, dd, J = 5.7 Hz, 12.1 Hz), 4.31 (1H, d, J = 11.5 Hz), 5.24 (1H, t-like), 5.78 (1H, s), 7.32 - 7.39 (3H, m), 7.49-7.52 (2H, m)

MC EI (m/z): 590 (M+)

1H-NMR (CDCl3) M. D. (compound 29)

0.95 (3H, s), 1.00 (3H, s), 1.01 (3H, s), 1.03 (3H, s), 1.08 (3H, s), 1.16 (3H, s), 1.48 (3H, s), 0.90-2.48 (20H, m), 2.99 (1H, d, J = 3.3 Hz), 3.40 (3H, s), 3.57 (1H, d, J = 3.3 Hz), 3.62 (1H, d, J = 11.1 Hz), 3.64 (1H, dd, J = 5.6 Hz, 12.1 Hz), 4.30 (1H, d, J = 11.1 Hz), 5.27 (1H, t-like), 5.79 (1H, s), 7.31-7.38 (3H, m), 7.49-7.52 (2H, m)

MC EI (m/z): 576 (M+)

1H-NMR (CDCl3) M. D. (compound 30)

0.92 (3H, s), 0.95 (3H, s), 0.96 (3H, s), 0.99 (3H, s), 1.08 (3H, s), 1.15 (3H, s), 1.43 (3H, s), 0.90-2.46 (20H, m), 2.91 (1H, d, J = 3.9 Hz), 3.44 (1H, d, J = 3.9 Hz), 3.47 (3H, s), 3.62 (1H, J = 10.8 Hz), 3.64 (1H, dd, J = 5.4 Hz, 12.1 Hz), 4.30 (1H, d, J = 10.3 Hz), 5.24 (1H, t-like), 5.78 (1H, s), 7.31-7.38 (3H, m), 7.49-7.52 (2H, m)

MC EI (m/z): 576 (M+)

Example 22

21 , 22 - Dimethoxytoluene-12-ene-3 , 24 (4)- diol (compound 31)

Compound 28 (20 mg) was dissolved in 1 ml methanol and 1 ml of dichloromethane and to the solution dobavlenie 1 hour. The reaction solution was filtered through brownmillerite and the filtrate was concentrated under reduced pressure to obtain 15 mg (yield: 89%) of compound 31 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), 0.93 (6H, s), 0.95 (3H, s), 1.02 (3H, s), 1.13 (3H, s), 1.25 (3H, s), 0.83-1.88 (18H, m), 2.18-2.21 (1H, m), 2.41 (1H, br s), 2.74 (1H, br s), 3.01 (2H, s), 3.32-3.50 (2H, m), 3.42 (3H, s), 3.45 (3H, s), 4.21 (1H, d, J = 11.3 Hz), 5.22 (1H, t-like),

MC EI (m/z): 502 (M+)

Example 23

22 - Metaxylem-12-ene-3 , 21 , 24 04)- triol (compound 32)

Compound 29 (13 mg) was dissolved in 1 ml methanol and 1 ml of dichloromethane and to the solution was added 5 mg of 10% Pd-C. the Mixture was catalytically restored at room temperature under atmospheric pressure for 2.5 hours. The reaction solution was filtered through brownmillerite and the filtrate was concentrated under reduced pressure to obtain 1 mg (yield; 68%) of compound 32 as a colourless solid,

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), 0.94 (3H, s), 0.96 (3H, s), 0.99 (3H, s), 1.02 (3H, s), 1.14 (3H, s), 1.25 (3H, s), 0.82-1.89 (19H, m), 2.25-2.31 (2H, m), 2.41 (lH, br s), 2.73 (1H, br s), 2.98 (1H, d, J = 3.3 Hz), 3.32-3.37 (1H, m), 3.40 (3H, s), 3.42-3.48 (1H, m), 3.56 (1H, d, J = 3.3 Hz), 4.21 (1H, d, J = 11.1 Hz), 5.24 (1H, t-like)

MC EI (m/z): 488 (M+)

Example 24

21-Metaxylem-12-EN-3,22,24(4 )-triol (compound 31)

Connection anaclinal at room temperature under atmospheric pressure for 1 hour. The reaction solution was filtered through brownmillerite and the filtrate was concentrated under reduced pressure to obtain 6 mg (yield: 80%) of compound 33 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), 0.91 (3H, s), 0.94 (3H, s), 0.95 (3H, s), 0.95 (3H, s), 1.13 (3H, s), 1.25 (3H, s), 0.82-2.18 (20H, m), 2.41 (1H, br s), 2.73 (1H, br s), 2.90 (1H, d, J = 4.0 Hz), 3.32-3.46 (3H, m), 3.46 (3H, s), 4.21 (1H, d, J = 11.1 Hz), 5.22 (1H, t-like)

MC EI (m/z): 488 (M+)

Example 25

3 , 24 (4), Benzyladenine-21,22-dioxoolean-12-ene (compound 34)

3 - 24 , Benzyladenine-22-dioxoolean-12-ene-21 ol (compound 35)

Oxalicacid (0.15 ml) was dissolved in 4 ml of dichloromethane and the solution was cooled to -78oC. a Solution of 0.25 ml of DMSO in 1 ml of dichloromethane was added to the cooled solution and the mixture was stirred for 10 minutes To the reaction solution was added dropwise a solution of 200 mg of compound 23 in 4 ml of dichloromethane and the mixture was stirred at -78oC for 15 minutes To the reaction solution was added to 0.74 ml of triethylamine and the mixture was stirred at -78oC for 5 minutes the temperature of the reaction solution was gradually raised to 0oC. thereto was added water and the mixture was extracted with dichloromethane, and the extract was washed with saturated aqueous salt solution and dried over Sul is to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, dichloromethane) to give 76 mg (yield: 37%) of compound 34 and 30 mg (yield: 15%) of compound 35 as a yellow solid.

1H-NMR (CDCl3) M. D. (compound 34)

0.98 (3H, s), 1.09 (3H, s), 1.14 (3H, s), 1.15 (3H, s), 1.16 (3H, s), 1.20 (3H, s), 1.49 (3H, s), 0.90-2.63 (19H, m), 3.62 (1H, d, J = 11.1 Hz), 3.64 (1H, dd,J = 5.3 Hz, 11.4 Hz), 4.29 (1H, d, J = 11.1 Hz), 5.41 (1H, t-like), 5.78 (1H, s), 7.31-7.39 (3H, m), 7.49-7.52 (2H, m)

MC EI (m/z): 558 (M+)

1H-NMR (CDCl3) M. D. (compound 35)

0.70 (3H, s), 0.97 (3H, s), 1.06 (3H, s), 1.09 (3H, s), 1.12 (3H, s), 1.27 (3H, s), 1.49 (3H, s), 0.91-2.49 (19H, m), 3.60-3.68 (3H, m), 4.19 (1H, d, J = 4.2 Hz), 4,30 (1H, d, J = 11.1 Hz), 5.32 (1H, t - like), 5.79 (1H, s), 7.30-7.40 (3H, m), 7.48-7.52 (2H, m)

MC EI (m/z): 560 (M+)

Example 26

21,22-Dioxoolean-12-ene-3 , 24 (4)- diol (compound 36)

Compound 34 (25 mg) was dissolved in 1 ml dichloromethane and 2 ml of methanol, to the solution was added 0.5 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 4 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silikagelja substances.

1H-NMR (CDCl3) M. D. (compound 34)

0.91 (3H, s), 0.94 (3H, s), 1.13 (3H, s), 1.14 (3H, s), 1.15 (3H, s), 1.18 (3H, s), 1.25 (3H, s), 0.80-2.75 (21H, m), 3.32-3.39 (1H, m), 3.41-3.49 (1H, m), 4.21 (1H, d, J = 11.0 Hz), 5.40 (1H, t-like)

MC FAB (m/z): 471 (M+H)+< / BR>
Example 21

22-Acooler-12-ene-3 , 21 , 24 (4)- triol (compound 37)

Compound 35 (25 mg) was dissolved in 1 ml dichloromethane and 2 ml of methanol, to the solution was added 0.5 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 4 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate =1:1) to give 13 mg (yield:61%) of compound 37 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.69 (3H, s), 0.90 (3H, s), 0.94 (3H, s), 1.05 (3H, s), 1.11 (3H, s), 1.25 (3H, s), 1.26 (3H, s), 0.80-2.73 (21H, m), 3.32-3.38 (1H, m), 3.42-3.49 (1H, m), 3.65 (1H, d, J = 4.1 Hz), 4.18 (lH, d, J = 4.1 Hz), 4.21 (1H, d, J = 11.2 Hz), 5.30 (1H, t-like)

MC FAB (M/3): 473 (M+)

Example 28

3 , 24 (4)- Benzylideneacetone-12-ene-21 , 22 - diol (compound 23)

3 , 24 (4)- benzylideneacetone-12-ene-21 , 22 - diol (connected to the -21 , 22 - diol (compound 40)

Lithium alumoweld (30 mg) suspended in 3 ml of anhydrous THF. To the solution under ice cooling was added dropwise a solution of compound 34 (193 mg) in 2 ml of anhydrous THF and the mixture was stirred for 2 hours. To the reaction solution was added a saturated solution of sodium sulfate and stirred for some time at room temperature. Insoluble substances were removed by filtration, the filtrate was concentrated under reduced pressure to obtain a concentrate, which was purified by column chromatography on silica gel (manifest system, n-hexane: THF = 3:1) to give 89 mg (yield: 461) mixture of compound 23, compound 38, 11 mg (yield: 5%) of compound 39 and 8 mg (yield: 4%) of compound 40.

1H-NMR (CDCl3) M. D. (compound 39)

0.85 (3H, s), 0.89 (3H, s), 0.95 (3H, s), 1.08 (6H, s), 1.10 (3H, s), 1.48 (3H, s), 0.85-2.48 (21H, m), 3.21-3.44 (2H, m), 3.60-3,68 (2H, m), 4.30 (1H, d, J = 11.3 Hz), 5.30 (1H, t-like), 5.78 (1H, s), 7.31 - 7.40 (3H, m), 7.48-7.53 (2H, m)

MC FAB (m/z): 585 (M+Na+)

1H-NMR (CDCl3) M. D. (compound 40)

0.91 (3H, s), 0.97 (3H, s), 1.00 (3H, s), 1.01 (3H, s), 1.07 (3H, s), 1.16 (3H, s), 1.48 (3H, s), 0.85-2,48 (21H, m), 3.27-3.35 (2H, m), 3.60-3.68 (2H, m), 4.30 (1H, d, j = 11.3 Hz), 5.25 (1H, t-like), 5.78 (1H, s), 7.30-7.39 (3H, m), 7.48-7.52 (2H, m)

MC FAB (m/z): 585 (M+Na+)

Example 29

Olean-12-ene-3 , 21 , 22 , 24 (4)- Teale 0.1 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 4 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate =1:1) to give 3 mg (yield: 34%) of compound 41 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.83 (3H, s), 0.87 (3H, s), 0.90 (3H, s), 0.91 (3H, s), 1.05 (3H, s), 1.08 (3H, s), of 1.23 (3H, s), 0.85-2.27 (23H, m), 3.20-3.35 (3H, m), 3.40-3.46 (1H, m), 4.19 (1H, d, J = 11.3 Hz), 5.26 (1H, t-like)

MC EI (m/z): 474 (M+)

Example 30

Olean-12-ene-3 , 21 , 22 , 24 (4)- tetraol (compound 42)

Compound 40 (9 mg) was dissolved in 0.5 ml dichloromethane and 1 ml of methanol, to the solution was added 0.1 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 4 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate - 1:1) to give 4 mg (yield: H, s), 0.90 (3H, s), 0.93 (3H, s), 0.99 (6H, s), 1.14 (3H, s), 1.25 (3H, s), 0.82-2.44 (21H, m), 3.00-3.05 (1H, m), 3.10-3.14 (1H, m), 3.22-3.47 (3H, m), 3.42 (1H, dd, J = 6.6 Hz, 11.0 Hz), 4.20 (1H, d, J = 11.0 Hz), 5.23 (1H, t-like)

MC EI (m/z): 474 (M+)

Example 31

21 - Acetoxy-3 , 24 (4), benzyladenine-22-acooler-12-ene (compound 43)

Compound 43 (49 mg, yield: 54%) was obtained from 91 mg of compound 25 in the same manner as in example 18.

1H-NMR (CDCl3) memorial plaques

0.86 (3H, s), 0.97 (3H, s), 1.03 (3H, s), 1.04 (3H, s), 1.08 (3H, s), 1.27 (3H, s), 1.49 (3H, s), 2.18 (3H, s), 0.90-2.49 (19H, m), 3.60 - 3.68 (2H, m), 4.30 (1H, d, J = 11.3 Hz), 5.32 (2H, t-like), 5.78 (1H, s), 7.31-7.40 (3H, m), 7.48-7.52 (2H, m)

MC EI (m/z): 602 (M+)

Example 32

21 - Acetoxy-3 , 24 (4), benzyladenine-22 - methyloxiran-12-ene (compound 44)

Compound 25 (316 mg) was dissolved in 8 ml of anhydrous pyridine, the solution was added 162 μl of methanesulfonanilide and a catalytic amount of 4-DMAP and the mixture was stirred at room temperature overnight. To the reaction solution was added ice water, the mixture was extracted with ethyl acetate and the extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a solid substance, which is then washed with a mixed solution of n-hexane and ethyl acetate to obtain , .10 (3H, s), 1.19 (3H, s), 1.49 (3H, s), 2.14 (3H, s), 0.93-2.48 (18H, m), 3.08 (3H, s), 3.60-3.68 (2H, m), 3.72-3.78 (1H, m), 4.30 (1H, d, J = 11.5 Hz), 4.59 (1H, d, J = 3.1 Hz), 4.97 (1H, d, J = 3.1 Hz), 5.30 (1H, t-like), 5.78 (1H, s), 7.30-7.39 (3H, m), 7.49-7.52 (2H, m)

MC FBL (m/h): 700 (M+NH4+)

Example 33

3 , 24 (4)- Benzylideneacetone-12-EN-21 - ol (compound 45)

Triethylborane hydride (1.0 M THF solution of 4.6 ml) was added to 315 mg of compound 44 while cooling on ice and the mixture was stirred at room temperature for 15 minutes To the reaction solution were added water and the mixture was extracted with ethyl acetate, and the extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 5: 1) to give 221 mg (yield: 88%) of compound 45 in the form of a foamy substance.

1H-NMR (CDCl3) memorial plaques

0.85 (3H, s), 0.94 (6H, s), 0.96 (3H, s), 1.08 (3H, s), 1.18 (3H, s), 1.48 (3H, s), 0.90-2.48 (22H, m), 3.47 (1H, br s), 3.62 (1H, d, J = 11.3 Hz), 3.64 (1H, dd, J = 5.1 Hz, 12.1 Hz), 4.30 (1H, d, J = 11.3 Hz), 5.24 (1H, t-like), 5.78 (1H, s), 7.30-7.39 (3H, m), 7.49-7.52 (2H, m)

MC FBL (m/z): 564 (M+NH4+)

Example 34

Olean-12-ene-3 , 21 , 24 (4)- triol (compound 46)

Compound 46 (18 mg, yield:46%) in the form of the be the/SUP>H-NMR (CDCl3) memorial plaques

0.84 (3H, s), 0.89 (3H, s), 0.92 (3H, s), 0.93 (6H, s), 1.16 (3H, s), 1.24 (3H, s), 0.86-2.48 (24H, m), 3.33 (1H, d, J= 11.3 Hz), 3.39-3.48 (2H, m), 4.20 (1H, d, J = 11.3 Hz), 5.22 (1H, t-like)

MC FBL (m/z): 476 (M+NH4+)

Example 35

3 , 24 (4), Benzylidene-21-acooler-12-ene (compound 47)

Compound 47 (56 mg, yield: 51%) as a colourless solid substance was obtained from 110 mg of compound 45 in the same manner as in example 25.

1H-NMR (CDCl3) M. D. (compound 34)

0.96 (3H, s), 0.98 (3H, s), 1.02 (3H, s), 1.08 (3H, s), 1.13 (3H, s), 1.21 (3H, s), 1.48 (3H, s), 0.90-2.50 (21H, m), 3.62 (1H, d, J = 11.3 Hz), 3.64 (1H, dd, J = 4.9 Hz, 12.6 Hz), 4.30 (1H, d, J = 11.3 Hz), 5.34 (1H, t-like), 5.79 (1H, s), 7.30-7.39 (3H, m), 7.49-7.53 (2H, m)

MC FAB (m/z): 567 (M+Na+)

Example 36

3 , 24 (4)- Benzylideneacetone-12-EN-21 - ol (compound 48)

Compound 48 (11 mg, yield: 20%) as a colourless solid was obtained from 55 mg of compound 47 in the same manner as in example 28.

1H-NMR (CDCl3) M. D. (compound 34)

0.86 (3H, s), 0.87 (3H, s), 0.96 (3H, s), 0.97 (3H, s), 1.08 (3H, s), 1.14 (3H, s), 1.48 (3H, s), 0.90-2.48 (22H, m), 3.52 (1H, dd, J = 4.6 Hz, 12.1 Hz), 3.62 (1H, d, J = 11.0 Hz), 3.64 (1H, dd, J = 5.1 Hz, 11.8 Hz) 4.30 (1H, d, J = 11.0 Hz), 5.23 (1H, t-like), 5.78 (1H, s), 7.30-7.39 (3H, m), 7.49-7.53 (2H, m)

MC FAB (m/z): 569 (M+Na+)

Example 37

Olean-12-ene-3 , 21 , 24 (4)- triol (compound 49)

Compound 49 (7 mg, yield: 82%) as bastun-NMR (CDCl3) memorial plaques

0.85 (3H, s), 0.86 (3H, s), 0.89 (3H, s), 0.92 (6H, s), 0.96 (3H, s), 1.12 (3H, s), 1.23 (3H, s), 0.83-2.21 (21H, m), 3.32 (1H, d, J = 11.0 Hz), 3.39-3.45 (1H, m), 3.50 (1H, dd, J = 5.6 Hz, 11.8 Hz), 4.19 (1H, d, J = 11.0 Hz), 5.21 (1H, t-like)

MC FBL (m/z): 459 (M+H)+< / BR>
Example 38

3 , 24 (4), Isopropylidenedioxy-22 - toiletsealed-12-ene (compound 50)

Compound 1 (500 mg) was dissolved in pyridine, the solution was added 287 mg p-toluensulfonate and a catalytic amount of 4-dimethylaminopyridine and the mixture was stirred at room temperature overnight. To the reaction solution was added water, the mixture was extracted with ethyl acetate and the extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 654 mg (yield 100%) of compound 50 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.76 (3H, s), 0.84 (9H, s), 0.94 (3H, s), 0.96 (3H, s), 1.10 (3H, s), 1.14 (3H, s), 1.21 (3H, s), 1.37 (3H, s), 1.44 (3H, s), 0.78-2.10 (21H, m), 2.45 (3H, s), 3.22 (1H, d, J = 11.65 Hz), 3.43-3.46 (1H, m), 4.03 (1H, d, J = 11.65 Hz), 4.34-4.37 (1H, m), 5.22 (1H, t-like)

MC FD (m/z): 652 (M+)

Example 39

3 , 24 (4)- Isopropylidenedioxy-12,21-diene (compound 51)

Triethylborohydride (a 1.0 M THF solution, 2 ml) was added to 65 mg of compound 50 by cooling on ice and the mixture premesis the reaction solution was added water, the mixture was extracted with ethyl acetate, and the extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a solid substance, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 10:1) to give 38 mg (yield: 79%) of compound 51 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.88 (3H, s), 0.96 (9H, s), 0.98 (3H, s), 0.99 (3H, s), 1.12 (3H, s), 1.17 (3H, s), 1.22 (3H, s), 1.38 (3H, s), 1.44 (3H, s), 0.90-2.13 (19H, m), 3.23 (1H, d, J = 11.54 Hz), 3.45-3.48 (1H, m), 4.05 (1H, d, J = 11.54 Hz), 5.20-5.32 (3H, m)

MC EI (m/z): 480 (M+)

Example 40

Olean-12,21-diene-3 , 24 (4)- diol (compound 52)

Compound 51 (48 mg) was dissolved in 1 ml methanol and 1 ml of dichloromethane, to the solution was added 0.5 ml of 1 N hydrochloric acid and the mixture was stirred for 1 hour. The reaction solution was diluted with dichloromethane, washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 36 mg (yield: 82%) of compound 52 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.87 (3H, s), 0.90 (3H, s), 0.94 (3H, s), 0.95 (3H, s), 0.98 (3H, s), 1.11 (3H, s), 1.25 (3H, s), 0.84-2.13 >/BR>Example 41

Olean-12-EN-3 24 (4) diol (compound 53)

Compound 51 (30 mg) was dissolved in 2 ml methanol and 1 ml of dichloromethane and to the solution was added 5 mg of 20% Pd(OH)2-C. a Mixture of catalytically recovered at atmospheric pressure during the night. The reaction solution was filtered and the filtrate was concentrated under reduced pressure to obtain 26 mg (yield: 93%) of compound 53 as a colorless solid.

1H-NMR (CDCl3) - M. D.

0.82 (3H, s), 0.87 (6H, s), 0.89 (3H, s), 0.93 (3H, s), 1.13 (3H, s), 1.25 (3H, s), 1.25 (3H, s), 0.78-2.03 (23H, m), 2.37 (1H, d, J = 4.16 Hz), 2.71 (1H, dd, J = 2.50 Hz, 8.88 Hz), 3.32-3.37 (1H, m), 3.42-3.48 (1H, m), 4.21 (1H, d, J = 10.88 Hz), 5.18 (1H, t-like)

MC EI (m/z): 442 (M+)

Example 42

3 ,-Benzoylacetone-12-EN-24 (4)- ol (compound 56)

Compound 53 (1,00 g of 2.26 mmol) was dissolved in 10 ml of pyridine. To the solution was added trailhead (881 mg, and 3.16 mmol) and the mixture is boiled under reflux for 5 hours. The solvent was removed through distillation, to the residue was added water and the mixture was extracted with ethyl acetate, the extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 1.5 g of compound 54 (crude product). Compound 54 (crude product, 1,5 and 2 hours. The reaction solution was diluted with dichloromethane, washed with water and dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 1.7 g of compound 55 (crude product). Compound 55 (crude product, 1.7 g) was dissolved in 20 ml of methanol and 50 ml of acetone. To the solution was added concentrated hydrochloric acid (0.5 ml) and the mixture was stirred at 70oC for 2 hours. The reaction solution is then neutralized 1 N sodium hydroxide and the solvent was removed through distillation. To the residue was then added water and the mixture was extracted with ethyl acetate, and the extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to get crude product which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 10:1) to give 818 mg (yield; 66%) of compound 56 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.84 (3H, s), 0.87 (3H, s), 0.88 (3H, s), 0.98 (3H, s), 1.14 (3H, s), 1.15 (3H, s), 1.60 (3H, s), 0.80-2.10 (24H, m), 3.59 (1H, t, J = 10.7 Hz), 4.26 (1H, dd, J = 11.7 Hz, 2.6 Hz), 4.92 (1H, dd, J = 8.6 Hz, 7.6 Hz), 5.19 (1H, t, J = 3.6 Hz), 7.43-7.60 (3H, m), 7.96-8.00 (2H, m).

56 (1.50 mg) was dissolved in 5 ml of dichloromethane, to the solution was added 71,1 mg chloromethylpyridine and the mixture was stirred for 1 hour. One hour after the start of mixing to the reaction solution was added a 71.1 mg chloromethylpyridine and the mixture was additionally stirred for 1 hour. To the reaction solution was added silica gel, followed by filtration. The filtrate was concentrated under reduced pressure to get crude product which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate =20:1) to give 142 mg (yield: 95%) of compound 57 as a colourless solid.

1H-NMR (CDCl3) memorial plaques

0.83 (3H, s), 0.88 (3H, s), 0.91 (3H, s), 0.96 (3H, s), of 1.16 (3H, s), 1.17 (3H, s), 1.58 (3H, s), 0.80-2.20 (23H, m), 4.93 (1H, dd, J = 11.4 Hz, 5.9 Hz), 5.20 (1H, t, J = 3.5 Hz), 7.41-7.59 (3H, m), 7.97-8.00 (2H, m), 10.23 (1H, s).

FABMS (m/z): 545 (M++1)

Example 44

24 (4)- Acooler-12-EN-3 - ol (compound 58)

Compound 57 (121 mg, 0,222 mmol) was dissolved in 3 ml of methanol and 4 ml of THF, the solution was added 0.5 ml of 1 N sodium hydroxide and the mixture was stirred for 3 hours. The reaction solution was neutralized 1 N hydrochloric acid and the solvent was removed through distillation. To the residue was added water, the mixture was extracted with ethyl acetate and extracranial the pressure to get the crude product, which then was purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 12:1) to obtain the 75,4 mg (yield: 77%) of compound 58 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.83 (3H, s), 0.87 (9H, s), 0.99 (3H, s), 1.14 (3H, s), 1.29 (3H, s), 0.80-2.10 (23H, m), 3.10-3.25 (2H, m), 5.19 (1H, t, J = 3.6 Hz), 9.77 (1H, d, J = 2.3 Hz).

FABMS (m/z): 441 (M++1)

Example 45

24 (4)- Metrolan-12-ene-3 , 24 (4)- diol (compound 59)

Compound 58 (50.0 mg, 0,114 mmol) was dissolved in 2 ml of THF and the solution was cooled to -78oC. To the solution at the same temperature was added an ethereal solution of MeLi (0,42 ml of 1.08 mmol/ml). The temperature of the mixture was gradually raised to 0oC for a period of 30 minutes, followed by stirring atoC for additional within 10 minutes To the reaction solution were added water and the mixture was extracted with ethyl acetate, and the extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to get crude product which was then purified by preparative TLC (manifest system, n-hexane: THF = 2,2:1) obtaining of 39.0 mg (yield: 75%) of compound 59 as a colorless solid.

1

FABMS (m/z): 479 (M++Na)

Example 46

3 - Benzisoxazole-12-EN-24 (4)- OIC acid (compound 60)

Compound 57 (300 mg) was dissolved in 15 ml of tert-butanol are added and to this solution was added at 2.93 ml of 2-methyl-2-butene. To the mixture was added a solution of 250 mg of sodium chlorite and 430 mg monolatry phosphate in 2 ml of water, and the mixture is then stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, the concentrate was extracted with ethyl acetate and the extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain oil, which was purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate =4:1) to give 261 mg (yield: 85%) of compound 60 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.84 (3H, s), 0.87 (3H, s), 0.88 (3H, s), 1.00 (3H, s), 1.01 (3H, s), 1.16 (3H, s), 1.37 (3H, s), 0.80-2.60 (23H, m), 4.81 (1H, dd, J = 12.3 Hz, 4.3 Hz), 5.21 (1H, t, J = 3.4 Hz), 7.40-7.58 (3H, m), 8.05-8.08 (2H, m)

FABMS (m/z): 583 (M++Na)

Example 47

Methyl{Olean-12-EN-3 - ol-24 (4) al} (compound 62)

The connection 60 (251 mg) was dissolved in 1 ml of methanol and 6 ml of THF, the solution domovladenie pH to 3 by adding 1 N hydrochloric acid and the solvent was removed through distillation. To the residue was added water, the mixture was extracted with ethyl acetate and the extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was dissolved in 6 ml methanol and 6 ml of THF. To this solution was added an excess amount of solution trimethylsilyldiazomethane and the mixture was stirred at room temperature for 1 min. the Reaction solution was concentrated under reduced pressure to get crude product which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 15:1) to give 136 mg (yield: 65%) of compound 62 in the form of a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.79 (3H, s), 0.83 (3H, s), 0.87 (3H, s), 0.98 (3H, s), 1.13 (3H, s), 1.41 (3H, s), 1.58 (3H, s), 0.80-2.10 (23H, m), 3.09 (1H, td, J = 12.0 Hz, 4.5 Hz), 3.34-3.38 (1H, m), 3.68 (3H, s), 5.19 (1H, t, J = 3.5 Hz).

FABMS (m/z): 583 (M++Na)

Example 48

24 (4)- Methyl-24 (4) acooler-12-EN-3 - ol (compound 63) and 24 (4), 24 (4) -Timeteller-12-ene-3 , 24 (4)- diol (compound 63)

Compound 62 (30.0 mg) was dissolved in 2 ml of THF and the solution was cooled to - 78oC. To the solution at the same temperature was added an ethereal solution of MeLi (0,71 ml of 1.08 mmol/Ali at room temperature for 4 hours. To the reaction solution was added water, the mixture was extracted with ethyl acetate and the extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to get crude product which was then purified using preparative TLC (manifest system, n-hexane: THF = 6:1) obtaining of 16.7 mg (yield: 58%) of compound 63 and 3.4 mg (yield: 11%) of compound 64 as a colorless solid.

1H-NMR (CDCl3) M. D. (compound 63)

0.81 (3H, s), 0.83 (3H, s), 0.87 (3H, s), 1.01 (3H, s), 1.14 (3H, s), 1.39 (3H, s), 1.59 (3H, s), 2.18 (3H, s), 0.80-2.20 (23H, m), 3.05 (1H, td, J = 11.9 Hz, 4.1 Hz), 3.18-3.22 (1H, m), 5.20 (1H, t, J = 3.6 Hz).

FABMS (m/z): 454 (M++Na)

1H-NMR (CDCl3) memorial plaques

0.83 (3H, s), 0.87 (6H, s), 1.02 (3H, s), 1.12 (3H, s), 1.19 (3H, s), 1.22 (3H, s), 1.41 (3H, s), 1.42 (3H, s), 0.80-2.40 (25H, m), 3.37 - 3.43 (1H, m), 5.21 (1H, t, J = 3.6 Hz).

FABMS (m/z): 493 (M++Na)

Example 49

22-Medienallee-12-EN-3-ol (compound 65)

Compound 58 (25 mg) was dissolved in 1 ml of THF, and to this solution at 0oC was added 0,57 ml of the reagent Tebbe 0.5 mmol/ml and the mixture was stirred at 0oC for 30 min and then at room temperature overnight. To the reaction solution was added diethyl ether and 1 N NaOH with subsequent filter what dilatatum and then dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to get crude product which was then purified using preparative TLC (manifest system, n-hexane: THF = 5:1) to obtain 17.9 mg (yield: 72%) of compound 65 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.83 (3H, s), 0.87 (6H, s), 0.93 (3H, s), 0.94 (3H, s), 1.14 (3H, s), 1.18 (3H, s), 0.80-2.10 (24H, m), 3.20-3.35 (1H, m), 5.09 (1H, dd, J = 17.6 Hz, 1.7 Hz), 5.17-5.24 (2H, m), 6.06 (1H, dd, J = 17.6 Hz, 11.2 Hz).

FABMS (m/z): (M++Na)

Example 50

21-Acooler-12-ene-3 , 24 (4)- diol (compound 66)

Compound 66 (6 mg, yield: 100%) was obtained from 7 mg of compound 47 in the same manner as in example 19.

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), 0.93 (3H, s), 0.94 (3H, s), 1.00 (6H, s), 1.11 (3H, s), 1.20 (3H, s), 1.25 (3H, s), 0.83-2.50 (23H, m), 3.34 (1H, d, J = 11.0 Hz), 3.45 (1H, dd, J = 3.8 Hz, 11.0 Hz), 4.21 (1H, d, J = 11.0 Hz), 5.32 (1H, t-like)

MC TSF (m/z): 474 (M++NH4+)

Example 51

22 Ethylmalonate-3 , 24 (4)- isopropylidenedioxy-12-ene (compound 67)

Compound 3 (100 mg) was dissolved in 3 ml of dichloromethane, to the solution was added 37 mg of 4-dimethylaminopyridine and 38 μl of ethylmaleimide and the mixture was stirred at room temperature for 30 minutes To the reaction solution dobarganes layer was washed with saturated salt solution and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate =5:1) to give 85 mg (yield: 67%) of compound 67 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.83 (3H, s), 0.90 (3H, s), 0.98 (3H, s), 0.99 (3H, s), 1.15 (3H, s), 1.16 (3H, s), 1.22 (3H, s), 1.28 (3H, t, J = 7.2 Hz), 1.38 (3H, s), 1.44 (3H, s), 0.86-2.21 (21H, m), 3.23 (1H, d, J = 11.5 Hz), 3.35 (2H, s), 3.46 (1H, dd, J = 4.6 Hz, 9.5 Hz), 4.05 (1H, d, J = 11.5 Hz), 4.19 (2H, q, J = 7.2 Hz), 4.73 (1H, t-like), 5.32 (1H, t-like)

MS TSF (m/h): 635 (M++Na+)

Example 52

22 - Malayasian-12-ene-3 , 24 (4)- diol (compound 68)

Compound 67 (73 mg) was dissolved in 5 ml ethanol and 1 ml of dichloromethane, to the solution was added 0.8 ml of 1 N sodium hydroxide and the mixture was stirred at room temperature for 1 hour. The reaction solution was acidified using 1 N hydrochloric acid and was extracted with dichloromethane. The extract was concentrated under reduced pressure. The concentrate was dissolved in 2 ml methanol and 1 ml of dichloromethane, to the mixture was added 0.5 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 30 minutes To the reaction solution were added water and the mixture extragere the filtrate was concentrated under reduced pressure to obtain 54 mg (yield: 83%) of compound 68 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.81 (3H, s), 0.87 (3H, s), 0.88 (3H, s), 0.91 (3H, s), 0.96 (3H, s), 1.12 (3H, s), 1-22 (3H, s), 0.84-2.20 (21H, m), 3.28-3.44 (2H, m), 3.33 (2H, s), 4.18 (lH, d, J = 11.3 Hz), 4.71 (1H, t-like), 5.22 (1H, t-like)

MC FAB (m/z): 567 (M++Na+)

Example 53

3 , 24 (4), Isopropylidenedioxy-22 -0 methoxycarbonyl propoxy-Olean-12-ene (compound 69)

Compound 3 (50 mg) was dissolved in 1 ml of anhydrous DMF, the solution was added 20 mg of 60% sodium hydride and the mixture was stirred at room temperature for 2.5 hours. Then to the reaction solution was added 87 μl trimethyl-4-bromocrotonate and the mixture was stirred at 50oC during the night. To the reaction solution were added ethyl acetate and the mixture was twice washed with water and dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a concentrate, which was then purified by column chromatography on silica gel (manifest system, n-hexane: ethyl acetate = 5:1) to give 15 mg (yield: 24%) of compound 69 in the form of a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.86 (3H, s), 0.88 (3H, s), 0.99 (3H, s), 1.00 (3H, s), 1.12 (3H, s), 1.16 (3H, s), 1.22 (3H, s), 1.38 (3H, s), 1.44 (3H, s), 0.82-2.13 (23H, m), 2.43 (2H, t, J = 7.2 Hz), 2.86-2.89 (1H, m), 3.16-3.22 (lH, m), 3.23 (1H, d, J = 11.5 Hz), 3.46 22 - Methoxycarbonylpropionyl-12-ene-3 , 24 (4)- diol (compound 70)

Compound 69 (15 mg) was dissolved in 1 ml of methanol and 0.5 ml of dichloromethane, to the solution was added 0.2 ml of 1 N hydrochloric acid and the mixture was stirred at room temperature for 15 minutes the Reaction solution was extracted with dichloromethane and the extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain 13 mg (yield: 94%) of compound 70 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.86 (3H, s), 0.87 (3H, s), 0.89 (3H, s), 0.94 (3H, s), 1.00 (3H, s), 1.11 (3H, s), 1.25 (3H, s), 0.83-2.13 (25H, m), 2.42 (2H, t, J = 7.2 Hz), 2.86-2.88 (1H, m), 3.16-3.22 (1H, m), 3.32-3.38 (1H, m), 3.42 - 3.48 (1H, m), 3.52-3.58 (1H, m), 3.67 (3H, s), 4.21 (1H, d, J = 11.0 Hz), 5.21 (1H, t-like)

MC TSF (m/z): 576 (M++NH+)

Example 55

Olean-12-ene-3 , 24 (4)- diol-22 - o-propanganda acid

Compound 70 (13 mg) was dissolved in 2 ml methanol and 1 ml of dichloromethane, to the solution was added 0.8 ml of 1 N sodium hydroxide and the mixture was stirred at room temperature for 10 hours. The reaction solution was acidified using 1 N hydrochloric acid and was extracted with dichloromethane, and the extract was dried over magnesium sulfate. Inorganic salt was removed by filtration and the filtrate concieve.

1H-NMR (CDCl3) memorial plaques

0.86 (3H, s), 0.88 (3H, s), 0.89 (3H, s), 0.94 (3H, s), 1-00 (3H, s), 1.11 (3H, s), 1.24 (3H, s), 0.82-2.12 (23H, m), 2.43 (2H, t, J = 7.2 Hz), 2.88-2.91 (1H, m), 3.20-3.26 (lH, m), 3.33 (lH, d, J = 11-0 Hz), 3.39-3.44 (1H, m), 3.53-3.60 (lH, m), 4.20 (lH, m), 5.22 (1H, t-like)

MC TSF (m/z): 543 (M-H)-< / BR>
Example 56

3 , 24 (4), Isopropylidenedioxy-22 - unlinkability-12-ene (compound 72)

Connection 3 (30.0 mg) was dissolved in 2 ml of pyridine, the solution was added 14 mg of phenylisocyanate and the mixture is boiled under reflux for 1 hour. To the reaction solution was added water, the mixture was extracted with ethyl acetate and the extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a solid substance, which was then purified using preparative TLC (manifest system, n-hexane: THF = 7:1) to obtain the 23,0 mg (yield: 62%) of compound 72 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.89 (3H, s), 0.92 (3H, s), 1.00 (3H, s), 1.02 (3H, s), 1.16 (6H, s), 1.23 (3H, s), 1.38 (3H, s), 1.44 (3H, s), 0.80-2.30 (21H, m), 3.23 (1H, d, J = 11.6 Hz), 3.46 (1H, dd, J = 9.3, 4.1 Hz), 4.05 (1H, d, J = 11.6 Hz), 4.65 (1H, t, J = 3.8 Hz), 5.27 (1H, t-like), 6.50 (1H, s), 7.05 (1H, t, J = 7.2 Hz), 7.28-7.42 (4H, m).

FABMS (m/z): 640 (M+Na)+< / BR>
Example 57

22 - Onlinecommunication-12th and the mixture was stirred at room temperature for 5 minutes The solvent was removed by distillation, to the residue was added a saturated solution of NaHCO3and the mixture was extracted with ethyl acetate. The extract was dried over sodium sulfate. Inorganic salt was removed by filtration and the filtrate was concentrated under reduced pressure to obtain a solid substance, which was then purified by preparative TLC (manifest system, n-hexane: THF = 2,5: 1) obtaining of 16.2 mg (yield: 87%) of compound 73 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.88 (3H, s), 0.90 (3H, s), 0.92 (3H, s), 0.95 (3H, s), 1.02 (3H, s), 1.15 (3H, s), 1.25 (3H, s), 0.80-2.70 (23H, m), 3.31-3.49 (2H, m), 4.21 (1H, dd, J = 11.4, 2.0 Hz), 4.65 (1H, t, J = 4.1 Hz), 5.26 (1H, t, J = 3.2 Hz), 6.49 (1H, s), 7.05 (1H, t, J = 7.4 Hz), 7.27-7.43 (4H, m)

FABMS (m/3): 600 (M+Na)+< / BR>
Example 58

22 - Aminocarboxylate-12-ene-3 , 24 (4)- diol (compound 74)

Connection 3 (5.6 mg) was dissolved in 0.2 ml of pyridine, the solution was added 4.2 mg dichloroethylidene and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain a solid substance. The solid substance was added methanol (0,558 ml) and the mixture was stirred at room temperature for 10 minutes the Solvent was removed by distillation, to the residue was added water licensing and the filtrate was concentrated under reduced pressure to obtain a solid substance, which then was purified using preparative TLC (manifest system, n-hexane: AcOEl = 1:1,5) to give 2.5 mg (yield: 44%) of compound 74 as a colorless solid.

1H-NMR (CDCl3) memorial plaques

0.84 (3H, s), 0.89 (3H, s), 0.90 (3H, s), 0.95 (3H, s), 1.00 (3H, s), 1.14 (3H, s), 1.25 (3H, s), 0.80-2.80 (23H, m), 3.32-3.48 (2H, m), 4.21 (1H, d, J = 11.0 Hz), 4.48-4.56 (3H, m), 5.24 (1H, t, J = 3.5 Hz)< / BR>
FABMS (m/z): 524 (M+Na)+< / BR>
Example formulation 1 Tablet

The compound of the present invention granularit through the process of wet granulation, the granulate add magnesium stearate and the mixture is compressed to obtain tablets. Each tablet has the following composition.

Connection 2 - 200 mg

Lactose 50 mg

Natrocarbonatite 20 mg

The hypromellose 5 mg

Magnesium stearate 3 mg

Only 278 mg

Example formulations of 2 Suppositories

Valappil H-15 was heated to 60oC, was added compound 2 and dispersively the melt and the variance of the completed forms for suppositories. The form of suppositories, filled dispersion was cooled to room temperature to obtain suppositories. Each suppository had the following composition.

Connection 2 - 200 mg

Values (in vitro)

The test compound was added to a concentration of 0.1 to 10 μg/ml to the cells Hep G2 in the presence of aflatoxin Bi(10-5M) and cells are then incubated in thermostat with a high content of CO2at 37oC for 48 hours. After incubation, the cells were stained Trifanova blue and assessed their ability to absorb paint using Monocellater (produced by Olympus Optical Co., Ltd.). Activity by suppression of hepatocytomegaly (%) was calculated by the following equation. In the equation the value for the control group is absorption (%) in the presence of one of aflatoxin B1and the value for the treated group, is absorption (%) at simultaneous presence of aflatoxin B1and tested the connection.

As a result, the activity to suppress hepatocytomegaly connections 2, 6, 10, 17, 20, 22, 26, 27, 32, 33, 36, 37, 46, 49, 66 and 73 amounted to not less than 5%.

< / BR>
Test Example 2

The effect on the model of hepatitis caused by concanavalin A (Con A)

Kohn A, dissolved in physiological saline solution was injected into mice male BALB/c mice (8 weeks old), weighing from 21 to 25 grams in a dose of 20 mg/kg to cause hepatitis. The test compound (compound 7) suspended in the mixture is of simmilarly, and this suspension was injected subcutaneously for 2 and 14 hours prior to the introduction of Con A in three doses i.e., 0.2 mg/mouse, 1.0 mg/mouse and 2.0 mg/mouse. Control group mice were injected one control media. Twenty-four hours after administration of Con A, the mice were killed ether anesthesia for studies on the activity of alanine aminotransferase (ALT) in plasma as an indicator of liver disease.

The results are shown in the drawing. Specifically, the ALT activity was 2068518 (u/l) for the group of mice that did not receive the test compound (control group), whereas the ALT activity was reduced to the same level as in the group of mice that did not receive Con A (that is, to the normal value), which is 5516 (u/l) for the group of mice that received the compound 7 at a dose of 1.0 mg/mouse, and the mice groups that received the connection 7 at a dose of 2.0 mg/mouse.

1. Pharmaceutical composition for treating hepatitis comprising as an active ingredient triterpene derivative of the General formula I or its salt

< / BR>
where R1represents a hydroxyl group, kilmetros, lower alkoxy or lower alkanoyloxy;

R2is lower alkenyl, CH2OR5where R>
represents a hydrogen atom or lower alkyl, or-CH2N(R7R8where R7and R8that may be the same or different, represent a hydrogen atom, lower alkyl, aryl or lower alkanoyl,

or R1and R2can connect to each other by the formation of - O-C(R9R10-O-CH2- where R9and R10that may be the same or different, represent lower alkyl or aryl;

R3and R4that may be the same or different, represent a hydrogen atom, hydroxyl group, hydroxymethyl, -N(R11R12where R11and R12represent the lowest alkanoyl, -OR13where R13represents lower alkyl, aralkyl, lower alkanoyl, arylcarbamoyl, aralkylamines or aryl(lower alkenyl)carbonyl;

X represents O, CH2.

2. Pharmaceutical composition for the treatment of hepatitis under item 1, where R1represents a hydroxyl group; R3represents a hydrogen atom, and X represents O.

3. Pharmaceutical composition for the treatment of hepatitis under item 1, where R1represents a hydroxyl group; R2represents hydroxymethyl; R3represents a hydrogen atom; R4the General formula Ia or its salt

< / BR>
where R1represents a hydroxyl group, lower alkoxy or lower alkanoyloxy;

R2represents hydroxymethyl, lower alkoxymethyl,

or R1and R2can be connected to each other to form-O-C(R14R15-O-CH2- where R14and R15represent lower alkyl;

R3and R4that may be the same or different, represent a hydrogen atom, hydroxyl group, hydroxymethyl, -N(R11R12where R11and R12represent the lowest alkanoyl, -OR13where R13represents lower alkyl, aralkyl, lower alkanoyl, arylcarbamoyl, aralkylamines or aryl(lower alkenyl)carbonyl;

X represents O, CH2,

provided that the compounds wherein R1represents a hydroxyl group, R2represents hydroxymethyl, R3represents a hydrogen atom, R4represents a hydroxyl group, and X represents O, are excluded.

5. The compound or its salt according to p. 4, where R1represents a hydroxyl group; R3represents a hydrogen atom, and X represents O.

6. The compound or its salt according to p. 4, where R1represents a hydroxyl group; R2represents the P> 7. Pharmaceutical composition for treating hepatitis comprising as an active ingredient triterpene derivative of the General formula II or its salt

< / BR>
where R16represents a hydroxyl group, kilmetros, lower alkoxy or lower alkanoyloxy;

R17is lower alkenyl, -CH2OR5where R5represents a hydrogen atom, arylmethyl, lower alkyl, formyl; -COOR6where R6represents a hydrogen atom; -CON(R29R30where R29and R30that may be the same or different, represent a hydrogen atom, lower alkyl, lower alkanoyl, aryl or aralkyl; -CH2N(R7R8where R7and R8that may be the same or different, represent hydrogen or lower alkyl; -C(R6)2OH, where R6represents hydrogen or lower alkyl, -COR6Awhere R6Arepresents lower alkyl, -CH2=CH2-,

or R16and R17can be connected to each other to form-O-C(R9R10-O-CH2- where R9and R10that may be the same or different, represent lower alkyl or aryl;

R18and R19that may be the same or different, before the sludge, aralkyl; -OCON(R29R30where R29and R30that may be the same or different and represent a hydrogen atom or aryl;

or R18and R19can be connected to each other to form oxo;

R20and R21respectively have the same meaning as R18and R19provided that R20and R21at the same time are not a hydrogen atom;

or R18and R20can be connected to each other to form-O[C(R9R10]p-O-, where R9and R10defined above, and p is an integer from 1 to 3;

Y represents O, CH2or the same relationship for the formation of a double bond in the ring to which Y is attached.

8. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, R17represents-CH2OH; R18and R20represent a hydrogen atom; R19and R21both represent a hydroxyl group and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

9. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or nistshave-OR13; R20represent a hydrogen atom; R21is-OR13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

10. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R17represents-CH2OR5; R18and R19are connected to each other to form oxo; R20and R21are connected to each other to form oxo and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

11. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R17represents-CH2OR5; R18and R19are connected to each other to form oxo; R20represents a hydrogen atom; R21represents a hydroxyl group and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

12. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or bottom20and R21are connected to each other to form oxo and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

13. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R17represents-CH2OR5; R18and R19represent a hydrogen atom; R20represents a hydrogen atom; R21represents a hydroxyl group, and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

14. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group; R17represents-CH2OR5; R18represents a hydrogen atom; R19represents a hydroxyl group or-OR13, R20represents a hydrogen atom; R21represents a hydroxyl group or-OR13and Y represents a single bond and, thus, represents O.

15. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R17represents-C(R; R20represents a hydrogen atom; R21represents a hydroxyl group or-OR13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

16. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R17is-COR6A; R18represents a hydrogen atom; R19represents a hydroxyl group or-OR13; R20represents a hydrogen atom; R21represents a hydroxyl group or-OR13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

17. Pharmaceutical composition for the treatment of hepatitis under item 7, where R16represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R17represents-CH=CH2; R18represents a hydrogen atom; R19represents a hydroxyl group or-OR13; R20represents a hydrogen atom; R21represents a hydroxyl group or or13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

18. Triterpene p is iloxi, lower alkoxy, excluding methoxy or lower alkanoyloxy, excluding acetoxy;

R17is lower alkenyl, -CH2OR5where R5represents a hydrogen atom, arylmethyl, lower alkyl, formyl, -COOR6where R6represents a hydrogen atom; -CON(R7R8where R7and R8that may be the same or different, represent a hydrogen atom, lower alkyl; -CH2N(R7R8where R7and R8that may be the same or different, represent hydrogen or lower alkyl; -C(R6)2OH, where R6represents hydrogen or lower alkyl; -COR6Awhere R6Ais lower alkyl; -CH2=CH2-,

or R16and R17can be connected to each other to form-O-C(R9R10-O-CH2- where R9and R10that may be the same or different, represent lower alkyl or aryl;

R18and R19that may be the same or different, represent a hydrogen atom, a hydroxyl group, kilmetros, -OR13where R13represents lower alkyl, aralkyl,

or R18and R19can be connected to each other to form oxo;

R20and R21military are not a hydrogen atom; -OCON(R29R30where R29and R30that may be the same or different and represent a hydrogen atom or aryl;

or R18and R20can be connected to each other to form-O[(R9R10] p-O-, where R9and R10defined above, and p is an integer from 1 to 3;

Y represents O, CH2or single bond for the formation of a double bond in the ring to which Y is attached, provided that the compounds wherein R16represents a hydroxyl group, R17represents-CH2OCH3; R20represents a hydroxyl group or methoxy; R18and R21both represent hydrogen atoms; R19represents hydroxyl or methoxy group, and Y represents a single bond, and compounds in which R16represents a hydroxyl group, R17represents-CH2OH, R20represents a hydroxyl group, R18, R19and R21represent a hydrogen atom, and Y represents a single bond, is excluded.

19. Connection on p. 18, where R16represents a hydroxyl group, lower alkoxy, including methoxy, or lower alkanoyloxy, including acetoxy; R17represents-CH2OR5; R21is-OR13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

20. Connection on p. 18, where R16represents a hydroxyl group, lower alkoxy, including methoxy, or lower alkanoyloxy, including acetoxy; R17represents-CH2OR5; R18and R19are connected to each other to form oxo; R20and R21are connected to each other to form oxo and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

21. Connection on p. 18, where R16represents a hydroxyl group, lower alkoxy, including methoxy, or lower alkanoyloxy, including acetoxy; R17represents-CH2OR5; R18and R19are connected to each other to form oxo; R20represents a hydrogen atom; R21represents a hydroxyl group and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

22. Connection on p. 18, where R16represents a hydroxyl group, lower alkoxy, including methoxy, or lower alkanoyloxy, including acetoxy; R17represents-CH2OR5

23. Connection on p. 18, where R16represents a hydroxyl group; R17represents-CH2OR5; R18represents a hydrogen atom; R19represents a hydroxyl group or-OR13; R20represents a hydrogen atom; R21represents a hydroxyl group or-OR13and Y represents a single bond and, thus, represents O.

24. Connection on p. 18, where R16represents a hydroxyl group, lower alkoxy, excluding methoxy or lower alkanoyloxy, excluding acetoxy; R17represents-C(R6)2OH; R18represents a hydrogen atom; R19represent a hydroxyl group or-OR13; R20represents a hydrogen atom; R21represents a hydroxyl group or-OR13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

25. Connection on p. 18, where R16represents a hydroxyl group, lower alkoxy, excluding methoxy or lower alkanoyloxy, excluding acetoxy; R17is-COR6A; R18represents a hydrogen atom; R19represents a hydroxyl group or-OR13; R20ary relationship for the formation of a double bond in the ring, to which Y is attached.

26. Connection on p. 18, where R16represents a hydroxyl group, lower alkoxy, excluding methoxy or lower alkanoyloxy, excluding acetoxy; R17represents-CH=CH2; R18represents a hydrogen atom; R19represent a hydroxyl group or-OR13; R20represents a hydrogen atom; R21represents a hydroxyl group or-OR13and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

27. Triterpene derivative of the General formula III or its salt

< / BR>
where R1, R2and Y have the meanings defined above;

R27is-OCON(R29R30where R29and R30have the above specified values; -OCO-(CH2)n-R16where R16defined above.

28. Triterpene derived by p. 27, where R1represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R2represents-CH2OR5; R27represents-OCO-(CH2)n-R16and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

29. Triterpene derived by p. 27, the t-CH2OR5and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

30. Triterpene derived by p. 27, where R1represents a hydroxyl group, lower alkoxy or lower alkanoyloxy; R2represents-CH2OR5; R27is-OCON(R29R30and Y represents a single bond for the formation of a double bond in the ring to which Y is attached.

31. Pharmaceutical composition for treating hepatitis comprising the compound according to any one of paragraphs.27-30 as the active ingredient.

32. Triterpene derivative of the General formula IV or its salt

< / BR>
where R1, R18, R19and Y have the meanings defined above;

R28is-CON(R29R30where R29and R30are defined above; -C(R6)OH, where R6defined above; -COR6Awhere R6Arepresents lower alkyl, or-CH=CH2.

33. Connection on p. 32, where R18and R19represent a hydrogen atom, a hydroxyl group or-OR13; R28is-CON(R29R30, R29and R30defined above, -C(R6)2OH, where R6determined to enter the surveillance of hepatitis, containing the compound according to any one of paragraphs.32 and 33 as the active ingredient.

 

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