Novel lipid compounds

FIELD: chemistry.

SUBSTANCE: invention relates to versions of a compound of formula where R1 is a hydrogen atom; R2 is a lower alkyl group; P is H; , where P1, P2 and P3 are identical or different and are selected from a hydrogen atom, a lower alkyl group and a C14-C22 alkenyl group substituted with a lower alkyl group; or where P1 is an alkenyl group, and each of P2 and P3 is a hydrogen atom; and Y is a C14-C22 alkenyl group with at least one double bond having a Z-configuration, and having a first double bond at the third carbon-carbon bond from the omega (ω)-end of the carbon chain, capable of lowering the level of triglycerides and cholesterol, a pharmaceutical or lipid composition based on the disclosed compounds, as well as use (versions) of the disclosed compounds.

EFFECT: high efficiency of using compounds.

32 cl, 6 dwg

 

The scope of the invention

The present invention relates to omega-3 lipid compounds of General formula (I):

where R1, R2, P, and Y are defined in the description.

The invention also relates to pharmaceutical compositions and lipid compositions containing such compounds, and such compounds for use as pharmaceuticals, in particular for the treatment of cardiovascular and metabolic diseases.

Background of invention

Dietary polyunsaturated fatty acids (PUFA)(Pufas) affect diverse physiological processes, affecting the normal health and chronic diseases, such as regulation of the levels of plasma lipids, cardiovascular and immune function, insulin action, and the development of neurons and visual function. The intake of polyunsaturated fatty acids (usually in the form of esters, e.g. in the form of glycerides or phospholipids) will lead to their distribution in almost every cell of the body, affecting the structure and function of membranes, the synthesis of eicosanoids, signal transmission in the cell and the regulation of gene expression. Fluctuations in the distribution of different fatty acids/lipids in various tissues, in addition to relatively specific cell lipid metabolism, and the expression is regulated is by fatty acids, transcription factor probably play an important role in establishing how cells respond to changes in the composition of polyunsaturated fatty acids. (Benatti, P. et al, J. Am. Coll. Nutr. 2004, 23, 281). Polyunsaturated fatty acids or their metabolites have been shown to modulate gene transcription by interaction with several nuclear receptors. There are activated proliferation peroxisome receptors (PPARs), hepatic nuclear factor-4 (HNF-4), X-receptor liver (LXR) and the receptor for 9-CIS-retinoic acid (retinoic X receptor, RXR). The processing of polyunsaturated fatty acids may also contribute to the regulation of the relative amounts of many transcription factors in the nucleus, including SREBP, NFkB, c/EBPβ and HIF-1α. These effects are not due to direct binding of fatty acids with a transcription factor, but rather includes the mechanisms that influence the content of the transcription factors in the nucleus. Regulation of gene transcription by fatty acids has a strong impact on cellular and tissue metabolism and creates the possibility of possible explanations involving interactions nutrient-gene in the occurrence and avoidance or mitigation of diseases such as obesity, diabetes, cardiovascular disorders, inflammatory diseases and malignant diseases (Wahle, J., et al., Proceedings of the Nutrition Society, 2003, 349). It has been shown that fish oil rich in omega-3 polyunsaturated fatty acids, eicosapentaenoic to what slotow (EPA) and docosahexaenoic acid (DHA), reduces the risk of cardiovascular disease, in part, by reducing the concentration of triglycerides in the blood. Specified favorable effect is the result, primarily, the combined effect of the processes of inhibition of lipogenesis by reducing SPEBP-1 and stimulation of fatty acid oxidation through activation of PPAR-α in the liver.

Due to their limited stability in vivo and the absence of their biological specificity, DHA has not achieved wide application as therapeutic agents. Chemical modification of n-3 polyunsaturated fatty acids were carried out by several research groups to change or increase their metabolic effects.

For example, lipid-lowering effects of EPA were strengthened by the introduction of methyl or ethyl in the α-position of the ethyl ester (EE) EPA. (Vaagenes et al. Biochemical Pharm. 1999, 58, 1133). These compounds also reduce the levels of free fatty acids in blood plasma, while compounds by EPA that IT has no such effect.

In the last work published by L. Larsen (Larsen, L. Et al., Lipids, 2005, 40, 49), the authors showed that the α-methyl derivatives of EPA and DHA increased activation of the nuclear receptor PPARα and, thus, the expression of L-FABP in comparison with EPA/DHA. The authors suggest that a slow catabolism of these α-methyl derivatives of DHA contributes to the increase of their who is Astia.

The invention

One purpose of the present invention is the provision of omega-3 lipid compounds with pharmaceutical activity.

This goal is achieved by the omega-3 lipid compound of formula (I):

where

R1and R2are the same or different and selected from hydrogen atom, hydroxy-group, alkyl group, halogen atom, alkoxygroup, alloctype, acyl group, alkenylphenol group, alkenylphenol group, aryl group, allylthiourea, alkoxycarbonyl group, carboxypropyl, alkylsulfonyl group, alkylsulfonyl group, amino group and alkylamino;

R represents a hydrogen atom,

where R1, R2and R3selected from a hydrogen atom, alkyl groups and C14-C22alkenylphenol group, where the alkyl and Alchemilla group optionally substituted by a hydroxy-group

or

and

Y is a C14-C22alkenylphenol group, at least one double bonds with E and/or Z configuration;

or its pharmaceutically acceptable complex, MES, salt or prodrug, provided that R1and R2are not at the same time, what about the hydrogen atom.

In particular, the present invention relates to omega-3 lipid compounds of formula (I), where

• Y is C16-C22alkenyl with 2-6 double bonds;

• Y is C16-C20alkenyl with 2-6 double bonds, interrupted methylene group in the Z-configuration;

• Y is C20alkenyl with 6 double bonds, interrupted methylene group in the Z-configuration;

• Y is C20alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration;

• Y is C16-C20alkenyl with 3-5 double bonds;

• Y is C16-C20alkenyl with 3-5 double bonds, interrupted methylene group in the Z-configuration;

• Y is C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration;

• Y is C16alkenyl with 3 double bonds in Z-configuration; or

• Y is C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration.

More specifically, the present invention relates to omega-3 lipid compound selected from the group consisting of:

• (all-Z)-4,7,10,13,16,19-docosahexaen-1-ol,

• (all-Z)-5,8,11,14,17-eicosapentaen-1-ol,

• (all-Z)-9,12,15-octadecatrienoic-1-ol,

• (all-Z)-7,10,13,16,19-docosapentaenoic-1-ol,

• (all-Z)-11,14,17-Alsatian-1-ol,

• (4E, 8Z, 11Z, 14Z, 17Z)-Hey who superteen-1-ol,

• (5E, 8Z, 11Z, 14Z, 17Z)-eicosapentaen-1-ol, and

• (4E, 7Z, 10Z, 13Z, 16Z, 19Z)-docosahexaen-1-ol,

or its pharmaceutically acceptable complex, MES, salt or prodrug,

where the above omega-3 lipid compound substituted at carbon 2, counting from the hydroxyl functional group, at least one Deputy chosen from:

hydrogen atom, hydroxy-group, alkyl group, halogen atom, alkoxygroup, alloctype, acyl group, alkenylphenol group, alkenylphenol group, aryl group, allylthiourea, alkoxycarbonyl group, carboxypropyl, alkylsulfonyl group, alkylsulfonyl group, amino group and alkylamino;

provided that:

• R1and R2are not simultaneously a hydrogen atom.

In typical embodiments of the invention, the omega-3 lipid compound selected from:

In connection according to the invention, the above alkyl group may be selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and n-hexyl; the above halogen atom may be fluorine; the above alkoxygroup may be selected from methoxy, ethoxy, propoxy, isopropoxy, sec-butoxy, phenoxy, benzyloxy, OCH2CF3and co2CH2Och3; above alkene the other group can be selected from allyl, 2-butenyl and 3-hexenyl; the above Alchemilla group can be selected from propargyl, 2-butinyl and 3-hexenyl; the above aryl group may be selected from benzyl groups and substituted benzyl groups; the above allylthiourea may be selected from methylthio, ethylthio, isopropylthio, phenylthio; the above alkoxycarbonyl group can be selected from methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and butoxycarbonyl; the above alkylsulfonyl group can be selected from methanesulfonyl, econsulting and isopropanolamine; the above alkylsulfonyl group may be selected from methanesulfonyl, acanalonia and isopropanolamine; and the above alkylamino may be selected from methylamino, dimethylamino, ethylamino, diethylamino.

In particular, R1and R2can be selected from a hydrogen atom; alkyl groups, for example, C1-C7alkyl group; alkoxygroup, for example, C1-C7alkoxygroup; allylthiourea, for example, C1-C7ancilliary; amino, alkylamino, for example, C1-C7alkylamino, alkoxycarbonyl group, for example, C1-C7alkoxycarbonyl group, and carboxypropyl.

For example, the above C1-C7alkyl group which may be methyl, ethyl or propyl; above C1-C7alkoxygroup can be methoxy, ethoxy or propoxy; the above C1-C7alkylthiophene may be methylthio, ethylthio or propylthio; above C1-C7alkylaminocarbonyl can be ethylamino or diethylamino.

According to the present invention, R represents a hydrogen atom, or

R represents

where R1, R2and R3selected from a hydrogen atom, alkyl groups and C14-C22alkenylphenol group, where the alkyl and Alchemilla group optionally substituted by a hydroxy-group, or

R represents

R represents

R represents

Examples of compounds according to the invention are those in which R represents hydrogen, and Y is a C20alkenyl with 6 double bonds, interrupted methylene group that has a Z-configuration, where:

one of the groups R1and R2is methyl, and the other is a hydrogen atom;

one of the groups R1and R2is ethyl and the other is a hydrogen atom;

one of the groups R1and R2is propyl and the other is a hydrogen atom;

one of the groups R1 and R2is methoxy, and the other is a hydrogen atom;

one of the groups R1and R2is ethoxy, and the other is a hydrogen atom;

one of the groups R1and R2is propoxy, and the other is a hydrogen atom;

one of the groups R1and R2is thiomethyl, and the other is a hydrogen atom;

one of the groups R1and R2is thioethyl, and the other is a hydrogen atom;

one of the groups R1and R2is thiopropyl, and the other is a hydrogen atom;

one of the groups R1and R2is ethylamino, and the other is a hydrogen atom;

one of the groups R1and R2is benzyl and the other is a hydrogen atom;

one of the groups R1and R2is diethylamino, and the other is a hydrogen atom; or

one of the groups R1and R2is amino and the other is a hydrogen atom.

Other examples of compounds according to the invention are those in which R is hydrogen, and Y is a C20alkenyl with 5 double bonds, interrupted methylene group that has a Z-configuration, where:

one of the groups R1and R2is methyl, and the other is a hydrogen atom;

one of the groups R1and R2is ethyl and the other is a hydrogen atom;

one of the groups R1and R2one is camping propyl, and the other is a hydrogen atom;

one of the groups R1and R2is methoxy, and the other is a hydrogen atom;

one of the groups R1and R2is ethoxy, and the other is a hydrogen atom;

one of the groups R1and R2is propoxy, and the other is a hydrogen atom;

one of the groups R1and R2is benzyl and the other is a hydrogen atom;

one of the groups R1and R2is thiomethyl, and the other is a hydrogen atom;

one of the groups R1and R2is thioethyl, and the other is a hydrogen atom; or

one of the groups R1and R2is thiopropyl, and the other is a hydrogen atom.

Other examples of compounds according to the invention are those in which R is hydrogen, and Y is a C18alkenyl with 5 double bonds, interrupted methylene group that has a Z-configuration, where:

one of the groups R1and R2is methyl, and the other is a hydrogen atom;

one of the groups R1and R2is ethyl and the other is a hydrogen atom;

one of the groups R1and R2is propyl and the other is a hydrogen atom;

one of the groups R1and R2is methoxy, and the other is a hydrogen atom;

one of the groups R1and R2is ethoxy, and the other is the atom of toroda;

one of the groups R1and R2is propoxy, and the other is a hydrogen atom;

one of the groups R1and R2is thiomethyl, and the other is a hydrogen atom;

one of the groups R1and R2is thioethyl, and the other is a hydrogen atom;

one of the groups R1and R2is thiopropyl, and the other is a hydrogen atom;

one of the groups R1and R2is ethylamino, and the other is a hydrogen atom;

one of the groups R1and R2is benzyl and the other is a hydrogen atom;

one of the groups R1and R2is diethylamino, and the other is a hydrogen atom; or

one of the groups R1and R2is amino and the other is a hydrogen atom.

Additional examples of compounds according to the invention are those in which R is hydrogen, and Y is a C16alkenyl with 3 double bonds, interrupted methylene group that has a Z-configuration, where:

one of the groups R1and R2is methyl, and the other is a hydrogen atom;

one of the groups R1and R2is ethyl and the other is a hydrogen atom;

one of the groups R1and R2is propyl and the other is a hydrogen atom;

one of the groups R1and R2is methoxy, and the other is a hydrogen atom;

one is th of the groups R 1and R2is ethoxy, and the other is a hydrogen atom;

one of the groups R1and R2is propoxy, and the other is a hydrogen atom;

one of the groups R1and R2is thiomethyl, and the other is a hydrogen atom;

one of the groups R1and R2is thioethyl, and the other is a hydrogen atom;

one of the groups R1and R2is thiopropyl, and the other is a hydrogen atom;

one of the groups R1and R2is ethylamino, and the other is a hydrogen atom;

one of the groups R1and R2is benzyl and the other is a hydrogen atom;

one of the groups R1and R2is diethylamino, and the other is a hydrogen atom; or

one of the groups R1and R2is amino and the other is a hydrogen atom.

In the omega-3 lipid compound of formula (I) according to the present invention, R1and R2may be the same or different. When these groups are different, the compounds of formula (I) can exist in stereoisomeric forms. It should be noted that the invention includes all optical isomers of compounds of formula (I) and mixtures thereof, including racemates. Therefore, the present invention includes, where Rxdiffers from R2the compounds of formula (I), which are racemic or enantiomeric number is passed, either in the form of (S)-or (R)-enantiomer.

The present invention also relates to omega-3 to the compound of formula (I) for use as a medicament or for diagnostic purposes, for example, positron emission tomography (PET). In addition, the compounds and compositions according to the present invention can be used as cosmetic products, in particular, as a local agent for skin. Such drugs can be used for various purposes, including the treatment of psoriasis.

In addition, the present invention relates to pharmaceutical compositions containing omega-3 lipid compound of formula (I). The pharmaceutical composition may contain a pharmaceutically acceptable carrier, excipient or diluent, or any combination thereof, and suitably may be formulated for oral administration, for example, in the form of a capsule, packet, sachet, in solid form or in powder form. A suitable daily dosage of the compounds of formula (I) is from 1 mg to 10 g of the above compound; from 50 mg to 1 g of the above compound, or from 50 mg to 200 mg of the above compound.

The present invention also relates to a lipid composition containing omega-3 lipid compound of formula (I). Appropriate is when omega-3 lipid compound is present in it is ncentratio, component of at least 60% of the mass. or, at least 80% of the mass. lipid composition. The lipid composition may also include omega-3 fatty alcohols or their prodrug, selected from (all-Z)-5,8,11,14,17-eicosapentaen-1-ol (EPA), (all-Z)-4,7,10,13,16,19-docosahexaen-1-ol (DHA), (all-Z)-6,9,12,15,18-heneicosane-1-ol (HPA) and/or (all-Z)-7,10,13,16,19-docosapentaenoic-1-ol (DPA) or their derivatives, that is, presented in the form of alpha-substituted derivatives and/or pharmaceutically acceptable an antioxidant, such as tocopherol.

In addition, the invention relates to the use of omega-3 lipid compounds of formula (I) to obtain medicines for:

• activation or modulation of at least one of the isoforms of the receptor (PPAR) human activated proliferation peroxisome, where specified activated proliferation peroxisome receptor (PPAR) is activated proliferation peroxisome receptor (PPAR)α and/or γ.

• treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes.

• reduce the level of insulin in blood plasma, blood glucose and/or triglycerides in the serum.

• treatment and/or prevention of type 2 diabetes.

• prevention and/or treatment of elevated levels of triglycerides, LDL-cholesterol (LDL and/or VLDL-cholesterol (VLDL).

• prevention and/or treatment of GI is lipidemias state, for example, hypertriglyceridemia (HTG).

• increase levels of HDL (HDL) in human serum.

• treatment and/or prevention of obesity or condition of being overweight.

• reduce body weight and/or prevent the body mass increase.

• treatment and/or prevention of diseases of fatty infiltration of the liver, for example, non-alcoholic fatty infiltration of the liver (NAFLD).

• treatment of insulin resistance, hyperlipidemia and/or obesity or condition of being overweight.

• getting medicines for the treatment and/or prevention of an inflammatory disease or condition.

The invention also relates to methods of treatment and/or prevention of the above listed conditions, comprising the administration to a mammal in need of necessary pharmaceutically active amount of a compound of formula (I).

In addition, the present invention encompasses methods of obtaining omega-3 lipid compounds of formula (I).

Detailed description of the invention

The study shows that the introduction of a substituent in the α-position of polyunsaturated fatty acids increases their affinity to nuclear receptors and, in particular, to the PPAR receptors. Because PPAR are key regulators of the activity of homeostasis and inflammation, most studies have focused on time is abotu synthetic ligands of PPAR.

Functional group carboxylic acid DHA is important for binding to the target of PPAR, but this insueta group may interfere with the drug to cross the cell membrane of the intestinal wall. In this regard, the functional group of carboxylic acids in medicinal products are often protected in the form of ester. The less polar ester group can cross the membranes of fat cells and in the bloodstream it can be hydrolyzed to the free acid by esterases in the blood.

It is also possible that the plasma enzymes hydrolyzing not specified esters fairly quickly, and that the conversion of ester to the free acid mainly occurs consistently in the liver. The same effect is observed for the ethyl esters of polyunsaturated fatty acids, which are hydrolyzed to the free acid in vivo.

Since the 2-substituted derivatives of polyunsaturated fatty acids have the potential for use in therapeutic purposes, the compounds according to the present invention are novel prodrugs of α-substituted fatty acids. These prodrugs can be improved therapeutic action, increased bioavailability and ability to cross the cell membrane.

Each subtype receptor PPAR shows a pattern of expression and p is Scrivania, except for certain biological activities. While PPAR-α and PPAR-γ is mainly present in liver and adipose tissue, respectively, PPAR-δ is widely expressed. Due to the different distribution of subtypes of the receptor PPAR, medicines, readying for these receptors, should focus on the fabric where desired, the receptor is expressed. The variation of the functional groups in addition to the variation in chain length and number of double bonds may give the compounds of the present invention, the property of tissue specificity.

Typical embodiments of the invention include omega-3 polyunsaturated alcohols, or their prodrugs, which are substituted in position 2. In addition, the lipid composition containing omega-3 compounds according to the invention, can reduce the levels of triglycerides and cholesterol, and at the same time to increase HDL levels (HDL). Pharmaceutical product according to the invention may also have a effective effect on inflammatory diseases, the development of the nervous system and visual function.

Nomenclature and terminology

Fatty acids are hydrocarbon straight chain having a carboxyl (COOH) group at one end (α) and (usually) methyl group from another (ω)-end. Fatty acids are named according to the position of the first double bond from the ω-end. Those who min ω-3 (omega-3) means, that the first double bond exists as the third carbon-carbon bond from the terminal CH3groups (ω) carbon chain. However, according to the chemical nomenclature, numbering of carbon atoms starts from α-end.

According to the present invention, the carboxyl group is replaced by a new functional group in the form of alcohol or its prodrugs.

As used in the description, the expression “double bond, methylene interrupted by a group” refers to the case when the methylene group located between the two separate double bonds in the carbon chain omega-3 lipid compounds.

In this description, the terms “2-substituted”, substituted in position 2, and “substituted at carbon 2, counted from the functional group of the omega-3 lipid compounds” refers to the substitution at the carbon atom marked 2 in accordance with the above numbering of the carbon chain. Alternatively, such a substitution may be termed “2-substitution”.

In this description, the term “omega-3 lipid compound” (corresponding to ω-3 or n-3) refers to the lipid connection with the first double bond at the third carbon from the ω-end of the carbon chain, as defined above.

The basic idea of the present invention is an omega-3 lipid compound of formula (I):

where

R1and R2are the same or different and selected from hydrogen atom, hydroxy-group, alkyl group, halogen atom, alkoxygroup, alloctype, acyl group, alkenylphenol group, alkenylphenol group, aryl group, allylthiourea, alkoxycarbonyl group, carboxypropyl, alkylsulfonyl group, alkylsulfonyl group, amino group and alkylamino;

R represents a hydrogen atom, or

R represents

where R1, R2and R3selected from a hydrogen atom, alkyl groups and C14-C22alkenylphenol group, where the alkyl and Alchemilla group optionally substituted by a hydroxy-group, or

R represents

R represents

R represents

; and

Y is a C14-C22alkenylphenol group, at least one double bonds with E and/or Z configuration;

or its pharmaceutically acceptable complex, MES, salt or prodrug, provided that R1and R2are not simultaneously a hydrogen atom.

The compound obtained is 2-substituted omega-3 lipid compound, i.e. omega-3 lipid compound, substituted in position 2 from Narodnogo atom carbon chain, counting from the carbonyl end. More specifically, the compound obtained is 2-substituted polyunsaturated omega-3 alcohol or its prodrug. Typically, prodrugs belong to the omega-3 lipid compounds of formula (II):

where

- R3is1-C6the alkyl.

Other typical prodrugs include:

Other typical embodiments of the invention include the following omega-3 derivatives, substituted in position 2:

• (all-Z)-4,7,10,13,16,19-docosahexaen-1-ol,

• (all-Z)-5,8,11,14,17-eicosapentaen-1-ol,

• (all-Z)-9,12,15-octadecatrienoic-1-ol,

• (all-Z)-6,9,12,15-octadecatetraenoic-1-ol,

• (all-Z)-7,10,13,16,19-docosapentaenoic-1-ol,

• (all-Z)-11,14,17-Alsatian-1-ol,

• (all-Z)-6,9,12,15,18,21-tetracosactide-1-ol,

• (4E, 8Z, 11Z, 14Z, 17Z)-eicosapentaen-1-ol,

• (5E, 8Z, 11Z, 14Z, 17Z)-eicosapentaen-1-ol,

• (all-Z)-8,11,14,17-Amstetten-1-ol, and

• (4E, 7Z, 10Z, 13Z, 16Z, 19Z)-docosahexaen-1-ol.

Among the possible substituents listed above relative to R1and R2, lower alkyl groups, particularly methyl and ethyl groups are preferred variant embodiment of the invention. Other typical substituents include the substituents as lower alkoxygroup or lower alkylthio PPI, for example, having 1-3 carbon atoms. Substitution or R1or R2any one of the abovementioned substituents, while the other is hydrogen, it is believed, leads to the most efficient result.

Typical omega-3 polyunsaturated lipids, which can be substituted in position 2, comprise (all-Z)-4,7,10,13,16,19-docosahexaen-1-ol, (all-Z)-5,8,11,14,17-eicosapentaen-1-ol, (all-Z)-7,10,13,16,19-docosapentaenoic-1-ol and (all-Z)-9,12,15-octadecatrienoic-1-ol. Suitable substituents include a hydrogen atom and lower alkyl groups, preferably having 1-3 carbon atoms and more preferably 2-3 carbon atoms.

Omega-3 lipid compounds, i.e. substituted omega-3 alcohols and their potential prodrugs divided into the following categories A-H:

Category a

(all-Z)-4,7,10,13,16,19-docosahexaen-1-ol, or its prodrug, substituted in position 2, counted from the functional group:

Y=C20alkenyl with 6 double bonds, interrupted methylene group in the Z-configuration.

Category

(all-Z)-5,8,11,14,17-eicosapentaen-1-ol, or its prodrug, substituted in position 2, counted from the functional group:

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration.

Category

(all-Z)-9,12,15-octadecatrienoic--ol or its prodrug, substituted in position 2, counted from the functional group:

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration.

Category D

(all-Z)-7,10,13,16,19-docosapentaenoic-1-ol, or its prodrug, substituted in position 2, counted from the functional group:

Y=C20alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration.

Category E

(4E, 8Z, 11Z, 14Z, 17Z)-eicosapentaen-1-ol, or its prodrug, substituted in position 2, counted from the functional group:

Y=C18alkenyl with 5 double bonds.

Category F

(all-Z)-11,14,17-Alsatian-1-ol or its prodrug, substituted in position 2, counted from the functional group:

Y=C18alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration.

Category G

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-docosahexaen-1-ol or its prodrug, substituted in position 2, counted from the functional group:

Y=C20alkenyl with 6 double bonds.

Category N

(5E, 8Z, 11Z, 14Z, 17Z)-eicosapentaen-1-ol or its prodrug, substituted in position 2, counted from the functional group:

Y=C18Elke the sludge with 5 double bonds,

where R is-CH2COOH.

Category I

α-Substituted omega-3 lipid compounds, where R represents:

where R1, R2and R3each is a hydrogen atom, and where R1, R2and Y are defined above in the description.

Category J

α-Substituted omega-3 lipid compounds, where R represents:

where R1, R2and R3each is a methyl group, and where R1, R2and Y are defined in the description above.

Category

α-Substituted omega-3 lipid compounds, where R represents:

where R1is an ethyl group substituted by a hydroxy-group, R2and R3each is a hydrogen atom, and where R1, R2and Y are defined above in the description.

Category L

α-Substituted omega-3 lipid compounds, where R represents:

where R1, R2and Y are defined in the description above.

Category M

α-Substituted omega-3 lipid compounds, where R represents:

where R1, R2and Y are defined in the description above.

Category N

α-Substituted omega-3 lipid compounds, where R represents:

where R 1, R2and R3each is a methyl group.

Category Of

α-Substituted omega-3 lipid compounds, where R represents:

where R1is alkenylphenol group, and R2and R3each is a hydrogen atom, and where R1, R2and Y are defined in the description above.

Category a - examples(1)-(8):

For all examples(1)-(8):

R is hydrogen.

Y is C20alkenyl with 6 double bonds, interrupted methylene group

(all-Z)-2-methyl-4,7,10,13,16,19-docosahexaen-1-ol (1)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (2)

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-propyl-4,7,10,13,16,19-docosahexaen-1-ol (3)

R1= propyl and R2= a hydrogen atom, or

R2= propyl and R1= hydrogen atom

(all-Z)-2-methoxy-4,7,10,13,16,19-docosahexaen-1-ol (4)

R1= methoxy and R2= a hydrogen atom, or

R2= methoxy and R1= hydrogen atom

(all-Z)-2-ethoxy-4,7,10,13,16,19-docosahexaen-1-ol (5)

R1 = ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

(all-Z)-2-propoxy-4,7,10,13,16,19-docosahexaen-1-ol (6)

R1= propoxy and R2= a hydrogen atom, or

R2= propoxy and R1= hydrogen atom

(all-Z)-2-thiomethyl-4,7,10,13,16,19-docosahexaen-1-ol (7)

R1= thiomethyl and R2= a hydrogen atom, or

R2= thiomethyl and R1= hydrogen atom

(all-Z)-2-thioethyl-4,7,10,13,16,19-docosahexaen-1-ol (8)

R1= thioethyl and R2= a hydrogen atom, or

R2= thioethyl and R1= hydrogen atom

Category b - examples(9)-(17):

For all examples(9)-(17):

R = hydrogen atom

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration.

(all-Z)-2-methyl-5,8,11,14,17-eicosapentaen-1-ol (9)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol (10)

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-propyl-5,8,11,14,17-eicosapentaen-1-ol (11)

R1= propyl and R2= a hydrogen atom, or

R2= cut the R 1= hydrogen atom

(all-Z)-2-methyl-5,8,l1,14,17-eicosapentaen-1-ol (12)

R1= methoxy and R2= a hydrogen atom, or

R2= methoxy and R1= hydrogen atom

(all-Z)-2-ethoxy-5,8,11,14,17-eicosapentaen-1-ol (13)

R1= ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

(all-Z)-2-propoxy-5,8,11,14,17-eicosapentaen-1-ol (14)

R1= propoxy and R2= a hydrogen atom, or

R2= propoxy and R1= hydrogen atom

(all-Z)-2-thiomethyl-5,8,11,14,17-eicosapentaen-1-ol (15)

R1= methylthio and R2= a hydrogen atom, or

R2= methylthio and R1= hydrogen atom

(all-Z)-2-thioethyl-5,8,11,14,17-eicosapentaen-1-ol (16)

R1= atillio and R2= a hydrogen atom, or

R2= atillio and R1= hydrogen atom

(all-Z)-2-thiopropyl-5,8,11,14,17-eicosapentaen-1-ol (17)

R1= propylthio and R2= a hydrogen atom, or

R2= propylthio and R1= hydrogen atom

Category C - examples(18)-(26):

For all examples(18)-(26):

R = hydrogen atom

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

(all-Z)-2-methyl-9,12,15-octadecatrienoic-1-ol (18)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(all-Z)-2-ethyl-9,12,15-octadecatrienoic-1-ol (19)

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-propyl-9,12,15-octadecatrienoic-1-ol (20)

R1= propyl and R2= a hydrogen atom, or

R2= propyl and R1= hydrogen atom

(all-Z)-2-methoxy-9,12,15-octadecatrienoic-1-ol (21)

R1= methoxy and R2= a hydrogen atom, or

R2= methoxy and R1= hydrogen atom

(all-Z)-2-ethoxy-9,12,15-octadecatrienoic-1-ol (22)

R1= ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

(all-Z)-2-propoxy-9,12,15-octadecatrienoic-1-ol (23)

R1= propoxy and R2= a hydrogen atom, or

R2= propoxy and R1= hydrogen atom

(all-Z)-2-thiomethyl-9,12,15-octadecatrienoic-1-ol (24)

R1= methylthio and R2= a hydrogen atom, or

R2= methylthio and R1= hydrogen atom

(all-Z)-2-thioethyl-9,12,15-octadecatrienoic-1-ol (25)

R1= atillio and R2= and the om hydrogen, or

R2= atillio and R1= hydrogen atom

(all-Z)-2-thiopropyl-9,12,15-octadecatrienoic-1-ol (26)

R1= propylthio and R2= a hydrogen atom, or

R2= propylthio and R1= hydrogen atom

Category D - examples(27)-(35):

For all examples(27)-(35):

R = hydrogen atom

Y=C20alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

(all-Z)-2-methyl-7,10,13,16,19-docosapentaenoic-1-ol (27)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(all-Z)-2-ethyl-7,10,13,16,19-docosapentaenoic-1-ol (28)

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-propyl-7,10,13,16,19-docosapentaenoic-1-ol (29)

R1= propyl and R2= a hydrogen atom, or

R2= propyl and R1= hydrogen atom

(all-Z)-2-methoxy-7,10,13,16,19-docosapentaenoic-1-ol (30)

R1= methoxy and R2= a hydrogen atom, or

R2= methoxy and R1= hydrogen atom

(all-Z)-2-ethoxy-7,10,13,16,19-docosapentaenoic-1-ol (31)

R1= ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

(all-Z)-2-propoxy-7,10,13,16,19-docosapentaenoic-1-ol (32)

R1= propoxy and R2= a hydrogen atom, or

R2= propoxy and R1= hydrogen atom

(all-Z)-2-thiomethyl-7,10,13,16,19-docosapentaenoic-1-ol (33)

R1= methylthio and R2= a hydrogen atom, or

R2= methylthio and R1= hydrogen atom

(all-Z)-2-thioethyl-7,10,13,16,19-docosapentaenoic-1-ol (34)

R1= atillio and R2= a hydrogen atom, or

R2= atillio and R1= hydrogen atom

(all-Z)-2-thiopropyl-7,10,13,16,19-docosapentaenoic-1-ol (35)

R1= propylthio and R2= a hydrogen atom, or

R2= propylthio and R1= hydrogen atom

Category E - examples(36)-(44):

For all examples(36)-(44):

Y = C18alkenyl with 5 double bonds

R = hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-methylacetophenone-1-ol (36)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-ethylacetophenone-1-ol (37)

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-propylacetate-1-ol (38)

R1= propyl and R2= a hydrogen atom, or

p> R2= propyl and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-methoxyacetophenone-1-ol (39)

R1= methoxy and R2= a hydrogen atom, or

R2= methoxy and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-ethoxyacetophenone-1-ol (40)

R1= ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-propeciacheapunder-1-ol (41)

R1= propoxy and R2= a hydrogen atom, or

R2= propoxy and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-dimethylacetophenone-1-ol (42)

R1= methylthio and R2= a hydrogen atom, or

R2= methylthio and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-diethylaminopentane-1-ol (43)

R1= atillio and R2= a hydrogen atom, or

R2= atillio and R1= hydrogen atom

(4E, 8Z, 11Z, 14Z, 17Z)-2-dipropylamino-1-ol (44)

R1= propylthio and R2= a hydrogen atom, or

R2= propylthio and R1= hydrogen atom

Category F - examples(45)-(54):

For all examples:

Y=C18alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

R = hydrogen atom

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(all-Z)-2-ethyl,2-hydroxymethyl-11,14,17-Alsatian-1-ol (45)

R1= ethyl and R2= hydroxy, or

R2= hydroxy and R1= ethyl

(all-Z)-2-methyl-11,14,17-Alsatian-1-ol (46)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(all-Z)-2-ethyl-11,14,17-Alsatian-1-ol (47)

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-propyl-11,14,17-Alsatian-1-ol (48)

R1= propyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(all-Z)-2-methoxy-11,14,17-Alsatian-1-ol (49)

R1= methoxy and R2= a hydrogen atom, or

R2= methoxy and R1= hydrogen atom

(all-Z)-2-ethoxy-11,14,17-Alsatian-1-ol (50)

R1= ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

(all-Z)-2-propoxy-11,14,17-Alsatian-1-ol (51)

R1= propoxy and R2= a hydrogen atom, or

R2= propoxy and R1= hydrogen atom

(all-Z)-2-thiomethyl-11,14,17-Alsatian-1-ol (52)

R1= methylthio and R = a hydrogen atom, or

R2= methylthio and R1= hydrogen atom

(all-Z)-2-thioethyl-11,14,17-Alsatian-1-ol (53)

R1= atillio and R2= a hydrogen atom, or

R2= atillio and R1= hydrogen atom

(all-Z)-2-thiopropyl-11,14,17-Alsatian-1-ol (54)

R1= propylthio and R2= a hydrogen atom, or

R2= propylthio and R1= hydrogen atom

Category G - examples(55)-(63):

For all examples(55)-(63):

Y=C20alkenyl with 6 double bonds

R = hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-metalcomplexes-1-ol (55)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-utildatasource-1-ol (56)

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-propilatsetat-1-ol (57)

R1= propyl and R2= a hydrogen atom, or

R2= propyl and R1= hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-methoxytoluene-1-ol (58)

R1= methoxy and R2= a hydrogen atom, or

R2= methoxy and R1= hydrogen atom

(4E, 7Z, 10Z, 13, 16Z, 19Z)-2-toxicologist-1-ol (59)

R1= ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-propositionalize-1-ol (60)

R1= propoxy and R2= a hydrogen atom, or

R2= propoxy and R1= hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-dimethyldioctadecyl-1-ol (61)

R1= methylthio and R2= a hydrogen atom, or

R2= methylthio and R1= hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-diethyltoluene-1-ol (62)

R1= atillio and R2= a hydrogen atom, or

R2= atillio and R1= hydrogen atom

(4E, 7Z, 10Z, 13Z, 16Z, 19Z)-2-dipropylacetamide-1-ol (63)

R1= propylthio and R2= a hydrogen atom, or

R2= propylthio and R1= hydrogen atom

Category N - examples(64)-(66):

For all examples(64)-(66):

Y=C18alkenyl with 5 double bonds

R = hydrogen atom

(5E, 8Z, 11Z, 14Z, 17Z)-2-methylacetophenone-1-ol (64)

R1= methyl and R2= a hydrogen atom, or

R2= methyl and R1= hydrogen atom

(5E, 8Z, 11Z, 14Z, 17Z)-2-ethylacetophenone-1-ol (65)

R1= ethyl and R2= a hydrogen atom, or

R2/sub> = ethyl and R1= hydrogen atom

(5E, 8Z, 11Z, 14Z, 17Z)-2-ethoxyacetophenone-1-ol (66)

R1= ethoxy and R2= a hydrogen atom, or

R2= ethoxy and R1= hydrogen atom

Category I - examples(67)-(69):

For all examples(67)-(69):

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-acetate (67)

Y is a C20alkenyl with 6 double bonds, interrupted methylene group,

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol-acetate (68)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-9,12,15-octadecatrienoic-1-ol-acetate (69)

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

Category J - examples(70)-(72):

For all examples(70)-(72):

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-pivaloate (70)

Y=C20alkenyl with 6 double bonds, interrupted methylene group

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol-pivaloate (71)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-9,12,15-octadecatrienoic-1-ol-pivaloate (72)

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

Category K - examples(73)-(75):

For all examples(73)-(75):

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-hemisuccinate (73)

Y=C20alkenyl with 6 double bonds, interrupted methylene group,

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol-hemisuccinate (74)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-9,12,15-octadecane the n-1-ol-hemisuccinate (75)

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

Category L - examples(76)-(78):

For all examples(76)-(78):

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-phosphonate (76)

Y=C20alkenyl with 6 double bonds, interrupted methylene group,

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol-phosphonate (77)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-9,12,15-octadecatrienoic-1-ol-phosphonate (78)

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

Category M - examples(79)-(81):

For all examples(79)-(81):

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-sulfonate (79)

Y=C20alkenyl with 6 double bonds, interrupted methylene group,

R1= ethyl and R2 = a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol-sulfonate (80)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-9,12,15-octadecatrienoic-1-ol-sulfonate (81)

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

Category N - examples(82)-(84):

For all examples(82)-(84):

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-tert-BUTYLCARBAMATE (82)

Y=C20alkenyl with 6 double bonds, interrupted methylene group,

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol-tert-BUTYLCARBAMATE (83)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-9,12,15-octadecatrienoic-1-ol-tert-b is talkabout (84)

Y=C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

Category O - examples(85)-(86):

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol (Z)-2-ethyl-5,8,11,14,17-eicosapentaenoate (85)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

(all-Z)-2-ethyl-5,8,11,14,17-eicosapentaen-1-ol (Z)-2-ethyl-5,8,11,14,17-eicosapentaenoate (86)

Y=C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration

R1= ethyl and R2= a hydrogen atom, or

R2= ethyl and R1= hydrogen atom

Methods for producing compounds according to the invention

Method (General)

All the alcohols according to the invention can be obtained from their corresponding carboxylic acids or esters under the conditions of recovery.

2-substituted omega-3 polyunsaturated esters or carboxylic acids can be restored to their corresponding alcohols by using a reagent that carries Hedrick carbonyl compound. Examples of such reducing reagents are sociallyengaged, such as LiAlH4, LiAlH2(OCH2CH2OCH3), LiAlH[OC(CH3)3]3or borhydride, such as LiBH4, Ca(BH4)2. Suitable solvents include diethyl ether or THF, which is usually used in this reaction recovery in anhydrous conditions.

Scheme (I)

In addition, the synthesis of 2-substituted ethyl (all-Z)-4,7,10,13,16,19-docosahexaenoic described in the patent application IB2006/001155.

Method II: the production of esters of omega-3 polyunsaturated alcohols

The most common methods for the synthesis of esters are the methods by reaction of alcohols with acid chloride or other activated carboxylic acid derivatives. Usually ways to obtain often use pyridine as the catalyst, when there is the interaction of alcohol with the acid chloride. 4-dimethylaminopyridine (DMAP) is also a viable option as a catalyst in this reaction. It is also possible to use the reaction of the Fischer esterification, in which alcohol interacts with the carboxylic acid in the presence of an acid catalyst.

Scheme (II) illustrates an example of retrieving prodrugs of omega-3 polyunsaturated alcohols.

Scheme (II)

Phosphonates, protected tert-bootrom can be obtained by reacting alcohols with di-tert-butyl-diisopropylphosphoramidite and hydrogen peroxide in the presence of tetrazole. The removal of the protective group using triperoxonane acid leads to phosphonates (scheme III).

Scheme (III)

Method IV: Getting sulfonates omega-3 polyunsaturated alcohols

The sulfonates can be obtained by reacting alcohols with pyridine × SO3as shown in scheme (IV).

Scheme (IV)

Method V: Getting omega-3 polyunsaturated esters of omega-3 polyunsaturated alcohols

The General method involves reacting one equivalent of a polyunsaturated fatty acid with one equivalent of polyunsaturated alcohol in the presence of EDC (hydrochloride of 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide) or another activator of carboxylic acids, and bases (such as triethylamine or diisopropylethylamine) in an appropriate solvent. An example is shown in scheme (V).

Scheme (V)

Carbonates can be obtained by reacting alcohol with di-tert-BUTYLCARBAMATE (Re-O-Re) in the presence of a base (such as DMAP)as shown in scheme (VI).

Scheme (VI)

The synthesis protocols

Getting 2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (lipid compound 2):

Ethyl 2-ethyl-4,7,10,13,16,19-docosahexaenoate

(PRB-2, 0,81 g, 2,11 mmol) in 5 ml dry THF was added to a stirred suspension of LAH (0,084 g, 2.21 mmol) in 15 ml of dry THF, the temperature of which was maintained at 0°C. the Resulting solution was stirred at 0°C in an inert atmosphere for 30 minutes, was added 10% NH4Cl (20 ml) and filtered through a low layer of celite. Layer was washed with water (20 ml) and heptane (20 ml)and the layers were separated. The aqueous phase was extracted with heptane (20 ml)and the combined organic layer was washed with saturated salt solution (20 ml) and dried (MgSO4). Purification with flash chromatography (heptane: EtOAc 9:1) was obtained 0.33 g (46%) indicated in the title compound as a colourless oil;1H NMR (200 MHz, CDCl3): δ 0,86-and 0.98 (m, 6H), 1.26 in-and 1.54 (m, 3H), 1,98-2,17 (m, 4H), was 2.76-2,90 (m, 10H), 3,51 (d, 2H), 5,27-of 5.48 (m, 12H);13C-NMR (50 MHz, CDCl3): δ 11,29, 14,18, 20,47, 23,33, 25,46, 25,54, 25,57, 25,58, 25,60, 28,41, 42,50, 65,05, 126,94, 127,78, 128,01, 128,02, 128,07, 128,11, 128,17, 128,20, 128,48, 128,99, 131,93; MS (elektrorazpredelenie): 365,3 [M+Na].

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-acetate

Acetylchloride (5,64 ml, 65,6 mmol) was added dropwise to a stirred mixture of (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (20.4 g, to 59.6 mmol) and pyridine (46 μl, 0.6 mmol) in dry THF (200 ml) at 0°C. the Mixture was left at room temperature and was stirred overnight. The reaction is asili a saturated solution of NaHCO 3(120 ml)and the resulting mixture was extracted with heptane (200 ml). The organic layer was washed with water (120 ml) and dried (Na2SO4). Purification with flash chromatography on silica gel with elution with a mixture of heptane/EtOAc 100:2.5 to 95:3-95:5 resulted in 18 g (79%) indicated in the title compound as a yellow oil.

1H NMR (300 MHz, CDCl3): δ of 0.90 (t, 3H, J=7.4 Hz), of 0.95 (t, 3H, J=7.5 Hz), 1,35 (q, 2H, J=7,2 Hz), 1,64 (kV, 1H, J=6.4 Hz), 2,02 (c, 3H), 2.05 is-2,11 (m, 4H), 2,74-2,84 (m, 10H), of 3.96 (d, 2H, J=5,9 Hz), 5,26-5,42 (m, 12H);13C-NMR (75 MHz, CDCl3): δ 11,2, 14,2, 20,5, 20,9, 23,6, 25,5, 25,6, 28,4, 39,3, 66,4, 127,0, 127,4, 127,8, 128,0, 128,1, 128,17, 128,19, 128,2, 128,5, 129,4, 132,0, 171,2 (4 - signals invisible); MS (elektrorazpredelenie): 407,3 [M+Na]+.

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-pivaloate

Pivaloate (71 μl, of 0.58 mmol) was added to a mixture of (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (200 mg, 0.59 mmol) and pyridine (0.05 ml, of 0.62 mmol) in dry CH2Cl2(2 ml)and the reaction mixture was stirred at room temperature in an atmosphere of N2within 42 hours. The reaction mixture was diluted with diethyl ether (50 ml), washed with water (20 ml) and saturated salt solution (20 ml), dried (Na2SO4) and was evaporated in vacuum. Flash chromatography on silica gel with elution with a mixture of heptane-heptane:EtOAc (100:1) received 195 mg (79%) indicated in the title compounds as a colorless liquid.

1H NMR (200 MHz, CDCl3 ): δ 0,87-of 0.95 (m, 6N), of 1.18 (s, N), 1,33-1,44 (m, 2H), 1,58-of 1.73 (m, 1H), 1,99 and 2.13 (m, 4H), 2,78-and 2.83 (m, 10H), of 3.96 (d, J=5.6 Hz, 2H), 5,23-of 5.48 (m, N); MS (elektrorazpredelenie): 449 [M+Na]+.

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-hemisuccinate

A mixture of (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (200 mg, 0.59 mmol), succinic acid anhydride (65.9 mg, 0.66 mmol) and DMAP (71,6 mg, 0.59 mmol) in dry DMF (2 ml) was stirred at room temperature in an atmosphere of N2within 18 hours. The reaction mixture was diluted with diethyl ether (50 ml), washed with 1 M HCl (20 ml) and saturated salt solution (20 ml), dried (Na2SO4) and was evaporated in vacuum. Flash chromatography on silica gel with elution with a mixture of heptane:EtOAc(95:5)-(4:1)-(1:1) received 89 mg (34%) indicated in the title compound as a yellow liquid.

1H NMR (200 MHz, CDCl3): δ 0,86 is 0.99 (m, 6H), 1,24-of 1.39 (m, 2H), 1,62 by 1.68 (m, 1H), 2,02 and 2.13 (m, 4H), 2,62-and 2.83 (m, 4H), 2.71 to and 2.83 (m, 10H)to 4.01 (d, J=5.8 Hz, 2H), 5,22-of 5.48 (m, 12H); MS (elektrorazpredelenie): 465 [M+Na]+, 441 [M-H]-.

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-phosphonate

Stage 1: (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-di-tert-butylphosphonate

The solution tetrazole in CH3CN (0.45 M, and 9.2 ml, 4.14 mmol) was added to a solution of (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (428 mg, 1.25 mmol) and di-tert-butyl-diisopropylphosphoramidite (0,635 ml, a 2.01 mmol) in dry CH2Cl (30 ml). After 130 minutes of stirring at room temperature in an atmosphere of N2the mixture was cooled to 0°C and 50% N2About2(150 ml) was added. The mixture was stirred for 2 hours at 0°C, diluted with CH2Cl2(100 ml) and washed with 10% Na2S2O3(30 ml × 2), water (30 ml), a saturated solution of NaHCO3(30 ml × 2) and saturated salt solution (30 ml), dried (Na2SO4) and was evaporated in vacuum. Flash chromatography on silica gel with elution with a mixture of heptane-heptane:EtOAc(95:5)-(9:1) received 139 mg (21%) indicated in the title compounds as a colorless liquid.

1H NMR (200 MHz, CDCl3): δ 0,86 is 0.99 (m, 6H), 1,24-of 1.42 (m, 2H), 1,46 (s, N), 1,54-of 1.65 (m, 1H), 1,99 with 2.14 (m, 4H), 2,79-and 2.83 (m, 10H), 3,85 (t, J=5,6, 2H), 5,23-5,5,42 (m, N); MS (elektrorazpredelenie): 557 [M+Na]+

Stage 2: (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-phosphonate

To a solution of di-tert-butylphosphonate (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (133 mg, 0.25 mmol) in dry CH2Cl2(25 ml) was added CF3COOH (of 0.26 ml, 3,40 mmol). The mixture was stirred for 4 hours and evaporated in vacuum. To the residue was added CH2Cl2(20 ml)and the mixture was evaporated in vacuum, receiving 102 mg (97%) specified in the connection header.

1H NMR (200 MHz, CDCl3): δ 0,86 is 0.99 (m, 6H), 1,31-of 1.45 (m, 2H), 1,62 by 1.68 (m, 1H), 2,02 is 2.10 (m, 4H), 2,79-and 2.83 (m, 10H), of 3.97 (t, J=5.3 Hz, 2H), 5,23-of 5.48 (m, 12H), 8,91 (users, 2H); MS (elektrorazpredelenie): 421 [M-N] -.

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-sulfonate

Pyridine × SO3(45% SO3, 0,19 g of 1.16 mmol) was added to a solution of (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (0.20 g, of 0.58 mmol) in dry THF (10 ml). The mixture was stirred at ambient temperature under inert atmosphere for 18 hours and was distributed between 1 M HCl (20 ml) and diethyl ether (20 ml). The aqueous phase was extracted with diethyl ether (20 ml), the combined organic extracts were washed with saturated salt solution (20 ml), dried (Na2SO4) and was evaporated in vacuum. The crude oil was purified flash chromatography on a short column of silica gel (EtOAc, then 10% of the Meon in EtOAc) and was obtained 0.12 g (50%) specified in the connection header in the form of a solid pale yellow color.

1H NMR (200 MHz, CDCl3): δ 0,86 (t, 3H), were 0.94 (t, 3H), of 1.23 to 1.37 (m, 2H), 1,60-1,75 m, 1H), 1,97-2,11 (m, 4H), 2,70-2,87 (m, 10H), 4,00 (d, 2H), to 5.21-of 5.45 (m, N); MS (elektrorazpredelenie): UAH 421,2 [M-N]-.

(all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol-tert-BUTYLCARBAMATE

Di-tert-BUTYLCARBAMATE (0,80 g, 3.65 mmol) was added to a solution of (all-Z)-2-ethyl-4,7,10,13,16,19-docosahexaen-1-ol (0.25 g, 0.73 mmol) and DMAP (0,089 g, 0.73 mmol) in dry CH2Cl2(10 ml) under inert atmosphere. The mixture was stirred at ambient temperature for three hours. Then, a mixture of rasba the Lyali CH 2Cl2(15 ml), washed with water (2×15 ml) and saturated salt solution (15 ml), dried (Na2SO4) and concentrated in vacuum. The crude oil was purified flash chromatography on silica gel (heptane:EtOAc 98:2), then flash chromatography with reversed-phase silica gel-C8(H2Oh, then H2A:CH3CN 50:50) to obtain the 0,016 g (5%) specified in the title compounds as colorless oils.

1H NMR (200 MHz, CDCl3): δ of 0.89 (t, 3H), of 0.95 (t, 3H), 1.32 to of 1.40 (m, 2H), 1,46 (c, 9H), 1,60-1,80 (m, 1H), 2,02 with 2.14 (m, 4H), was 2.76-to 2.85 (m, 10H), of 3.95 (d, 2H), 5,23-of 5.48 (m, 12H); MS (elektrorazpredelenie): 465,3 [M+Na].

The invention is not limited to the above variants of carrying out the invention and examples.

1. The compound of formula (I):

where R1represents a hydrogen atom;
R2represents a lower alkyl group;
P represents H;

where R1P2and P3are the same or different and selected from a hydrogen atom, a lower alkyl group, and C14-C22alkenylphenol group, a substituted lower alkyl group;



where P1represents alkenylphenol group, and each of P2and P3represents a hydrogen atom is; and
Y is a C14-C22alkenylphenol group, at least one double bond with Z-configuration, and having a first double bond at the third carbon from the omega (ω)end of the carbon chain.

2. The compound according to claim 1, where Y is C14-C22alkenyl with 2-6 double bonds.

3. The compound according to claim 1, where Y is C20alkenyl with 6 double bonds, interrupted methylene group.

4. The compound according to claim 1, where Y is C18alkenyl with 5 double bonds, interrupted methylene group.

5. The compound according to claim 1, where Y is C14-C20alkenyl with 3-5 double bonds.

6. The compound according to claim 1, where Y is C16alkenyl with 5 double bonds, interrupted methylene group.

7. The compound according to claim 1, where Y is C14alkenyl with 3 double bonds, interrupted methylene group.

8. The compound according to any one of the preceding paragraphs, where the specified R2selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and n-hexyl.

9. The connection of claim 8, where the specified R2selected from methyl, ethyl, n-propyl.

10. The compound according to claim 1, where P represents H.

11. The compound according to claim 1 in racemic form.

12. The compound according to claim 1 in the form of its R-stereoisomer.

13. The compound according to claim 1 in the form of its S-stereoisomer.

14. The connection is .1, where R represents:

where P1P2and P3selected from a hydrogen atom, a lower alkyl group, and C14-C22alkenylphenol group, a substituted lower alkyl group;



where P1represents alkenylphenol group, and each of P2and P3represents a hydrogen atom; and
where Y is selected from C20alkenyl with 6 double bonds, interrupted methylene group in the Z-configuration; C18alkenyl with 5 double bonds, interrupted methylene group in the Z-configuration, and C16alkenyl with 3 double bonds, interrupted methylene group in the Z-configuration, and having a first double bond at the third carbon from the omega(ω)end of the carbon chain, and R1is a hydrogen atom, and R2is a methyl or ethyl group.

15. The compound of formula (I)

where R1represents a hydrogen atom;
R2represents a lower alkyl group;
R represents
Y is selected from C18alkenylphenol group with 5 double bonds, interrupted methylene group in the Z-configuration, and C20alkenylphenol group is 6 double bonds, interruptible methylene group in the Z-configuration, and having a first double bond at the third carbon from the omega (ω)end of the carbon chain.

16. The compound of formula (I):

where R1represents a hydrogen atom;
R2represents a lower alkyl group;
R represents
where P1P2and P3selected from a hydrogen atom, a lower alkyl group, and C14-C22alkenylphenol group, a substituted lower alkyl group; and
Y is selected from C18alkenylphenol group with 5 double bonds, interrupted methylene group in the Z-configuration, and C20alkenylphenol group with 6 double bonds, interrupted methylene group in the Z-configuration, and having a first double bond at the third carbon from the omega (ω)end of the carbon chain.

17. The compound of formula (I):

where R1represents a hydrogen atom;
R2represents a lower alkyl group;
P represents H; and
Y is selected from C18alkenylphenol group with 5 double bonds, interrupted methylene group in the Z-configuration, and C20alkenylphenol group with 6 double bonds, interrupted methylene group in the Z-configuration, and having a first double bond at the third is glared carbon from the omega (ω)end of the carbon chain.

18. The compound of formula (I):

where R1represents a hydrogen atom;
R2represents a lower alkyl group;
P is a
Y is selected from C18alkenylphenol group with 5 double bonds, interrupted methylene group in the Z-configuration, and C20alkenylphenol group with 6 double bonds, interrupted methylene group in the Z-configuration, and having a first double bond at the third carbon from the omega (ω)end of the carbon chain.

19. Connection PP-18, where the specified R2represents a methyl or ethyl group.

20. Pharmaceutical composition for treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, elevated levels of triglycerides and levels of non-HDL cholesterol (non-HDL) levels (LDL and/or VLDL-cholesterol) LDL and/or VLDL), gipolipidemicheskoe state, such as hypertriglyceridemia (HTG) and/or hyperlipidemia, obesity or condition of overweight, disease fatty infiltration of the liver, such as nonalcoholic fatty infiltration of the liver (NAFLD), to reduce the levels of insulin in the blood plasma, blood glucose and/or triglycerides serum, to increase levels of HDL (HDL) in human serum or for reducing body weight and/or for the of avoiding the addition of body mass, containing the compound according to any one of claims 1 to 19.

21. The pharmaceutical composition according to claim 20, also containing a pharmaceutically acceptable carrier, excipient or diluent, or any combination thereof.

22. The pharmaceutical composition according to claim 20 or 21, prepared for oral administration.

23. The pharmaceutical composition according to item 22 in the form of a capsule, packet, sachet, in solid form or in powder form.

24. The pharmaceutical composition according to claim 20, designed to provide a daily dose of from 1 mg to 10 g, for example from 1 mg to 1 g, for example from 1 mg to 500 mg, for example from 50 mg to 250 mg of the above compound.

25. The pharmaceutical composition according to claim 20, for use as pharmaceuticals.

26. Lipid composition for the treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, elevated levels of triglycerides and levels of non-HDL cholesterol (non-HDL) levels (LDL and/or VLDL-cholesterol) LDL and/or VLDL), gipolipidemicheskoe state, such as hypertriglyceridemia (HTG) and/or hyperlipidemia, obesity or condition of overweight, disease fatty infiltration of the liver, such as nonalcoholic fatty infiltration of the liver (NAFLD), to reduce the levels of insulin in the blood plasma, blood glucose and/or triglycerides serum, to increase levels of HDL (HDL) in human serum or for whom Nigeria body mass and/or to prevent the body mass increase, containing at least 60%, such as at least 70%, such as at least 80 wt.%, the lipid composition of the compound according to any one of claims 1 to 19.

27. Lipid composition on p, also contain omega-3 polyunsaturated lipid selected from (all-Z)-5,8,11,14,17-eicosapentaen-1-ol (EPA) and (all-Z)-6,9,12,15,18-heneicosane-1-ol (NDA).

28. The lipid composition according to any one of p-27, also containing a pharmaceutically acceptable antioxidant.

29. Lipid composition on p, where the specified antioxidant is tocopherol.

30. Lipid composition on p for use as a medicine.

31. The use of compounds according to any one of claims 1 to 19 for obtaining a medicinal product for the treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, such as type 2 diabetes, elevated levels of triglycerides and levels of non-HDL cholesterol (non-HDL) levels (LDL and/or VLDL-cholesterol) LDL and/or VLDL), gipolipidemicheskoe state, for example, hypertriglyceridemia (HTG) and/or hyperlipidemia, obesity or condition of overweight or disease fatty infiltration of the liver, for example, non-alcoholic fatty infiltration of the liver (NAFLD).

32. The use of compounds according to any one of claims 1 to 19 for receiving drugs to reduce levels of insulin plasma glucose in to the Ovi and/or serum triglycerides, to increase levels of HDL (HDL) in human serum or for reducing body weight and/or to prevent the body mass increase.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to an industrial method of producing polyprenyl phosphates having general structural formula:

, where each isoprene unit contains 5 carbon atoms, W denotes a ω-end isoprene unit, T denotes a trans-isoprene unit, C denotes a cis-isoprene unit, S denotes a 2,3-dihydroisoprene unit, a=0-10, b=0-39, c=0-1, a+b+c=4-40, X denotes a group of the formula OPO3MM', wherein M and M' are identical or different and are a hydrogen cation or a monovalent inorganic or organic cation, or M and M' together are a divalent inorganic cation. The disclosed method involves phosphorylation of the corresponding polyprenol or a mixture of oligomer homologues of the given formula, where X is replaced with a hydroxy group, substituted by an ammonium salt of phosphoric acid in the presence of a condensing agent in a medium of a first aprotic organic solvent; and the reaction mixture is extracted and precipitated, while separating polyprenyl phosphate in form of mono- or di-substituted salts thereof with monovalent inorganic or organic cations or salts thereof with divalent inorganic cations.

EFFECT: novel, efficient and cheap method of producing polyprenyl phosphates.

20 cl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a biocidal composition containing hydrogen peroxide in concentration of 0.05-50% (wt/wt) and a compound of formula 1: (OH)(2-m)(X)(O)P-[(O)p-(R')q-(CH(Y)-CH2-O)n-R]m, where X is H or OH; each Y is independently H or CH3; m equals 1 and/or 2; each p and q is independently equal to 0 or 1, provided that if p equals 0, q equals 1; each n is independently equal to 2-10; each R' is independently an alkylene radical containing 1-18 carbon atoms; each R is independently H or an alkyl radical containing 1-18 carbon atoms; and R'+R≤20; in concentration of 0.01-60% (wt/wt), as a biocidal composition. The invention also relates to use of the disclosed composition as a biocidal composition, as well as for purposes where there is need for disinfection and/or sanitation activity.

EFFECT: composition has excellent biocidal activity.

25 cl, 9 tbl, 10 ex

The invention relates to the chemistry of organophosphorus compounds, and in particular to an improved process for the preparation of dimethyl-[1-(1-fenilalaninammonii)-Pro-penyl-2]-phosphate (citrine), which insectoacaricidal

FIELD: chemistry.

SUBSTANCE: invention relates to method of removing alkanol admixture from flow, containing organic carbonate and alkanol admixture, which includes contact of flow with catalyst for influence on reaction of alkanol admixture with organic carbonate, where organic carbonate is represented by di(C1-C5)alkylcarbonate; or di(C5-C7)arylcarbonate; or (C1-C5)alkyl(C5-C7)arylcarbonate; or cyclic (C1-C10)alkylenecarbonate or their mixture; and where alkanol admixture is represented by alkoxy alkanol.

EFFECT: invention relates to method of obtaining diarylcarbonate, which includes contact of flow which contains dialkylcarbonate and alkanol admixture, with catalyst for impact on reaction of alkanol admixture with dialkyl carbonate by said method, and after that, contact of aryl alcohol in presence of re-etherification catalyst with dialkylcarbonate-containing flow.

11 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method for distillation purification of diaryl carbonates of general formula (I) where R, R' and R" independently represent a hydrogen atom, a straight-chain or branched alkyl with 1-34 carbon atoms, an alkoxy with 1-34 carbon atoms, a cycloalkyl with 5-34 carbon atoms, an alkylaryl with 7-34 carbon atoms, an aryl with 6-34 carbon atoms or a halogen radical. R, R' and R" on both sides of formula (I) can be identical or different, and R can also denote -COO-R"', wherein R'" can represent a hydrogen atom; an alkyl with 1-34 carbon atoms, an alkoxy with 1-34 carbon atoms, a cycloalkyl with 5-34 carbon atoms, an alkylaryl with 7-34 carbon atoms or an aryl with 6-34 carbon atoms, in at least one distillation column, having at least one enriching part in the top part of the column and at least one distillation part in the bottom part of the column, where the diaryl carbonate to be purified is obtained by re-esterification of at least one dialkyl carbonate and at least one aromatic hydroxyl-containing compound of general formula (III) where R, R' and R" can independently assume values given or general formula (I), in the presence of at least one re-esterification catalyst and which contains as an impurity, a catalyst used to produce diaryl carbonate, and the purified diaryl carbonate is removed in the side stream of the first distillation column, the first distillation column being a column with a dividing wall.

EFFECT: easy to implement method provides energy-efficient removal of catalyst residues and impurities of high-boiling secondary components.

15 cl, 3 ex, 11 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing diaryl carbonate coupled with electrolysis of the formed alkali metal chloride-containing spent aqueous solutions. The method of producing diaryl carbonate and treating at least a portion of the formed alkali metal chloride-containing solution comprises the following steps: a) reacting phosgene, obtained from reacting chlorine with carbon monoxide, with at least one monophenol in the presence of a base and, optionally, in the presence of a base catalyst to form diaryl carbonate and an alkali metal chloride-containing solution, b) separating and extracting the diaryl carbonate formed at step (a), c) separating the alkali metal chloride-containing solution remaining after step (b) from solvent residue and, optionally, catalyst residue with subsequent treatment with adsorbents, wherein before treatment with adsorbents, pH of the alkali metal chloride-containing solution is set equal to or lower than 8, d) electrochemical oxidation of at least a portion of the alkali metal chloride-containing solution from step (c), which takes place with formation of chlorine, an alkali metal hydroxide solution and in the corresponding case hydrogen, wherein at least a portion of the obtained chlorine is used to produce phosgene and/or e) returning at least a portion of the alkali metal hydroxide solution obtained at step (d) to step (a) for producing diaryl carbonate, where at least a portion of the alkali metal chloride-containing solution formed at step (c) is returned to step (a).

EFFECT: along with other advantages, the disclosed method improves recycling through electrolysis of the alkali metal chloride-containing solution formed when producing diaryl carbonate.

12 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing a fluorine-containing compound, having a carbonate bond, which involves reacting a compound of formula (1) in which X1-X6 denote a chlorine atom, with a fluorine-containing compound, having at least one OH group, in the presence of a catalyst, to obtain a fluorine-containing compound having a carbonate bond, where the fluorine-containing compound having at least one OH group is a polyfluoroalkane monool having 2-10 carbon atoms, which does not have a fluorine atom in the α-position and can have an oxygen atom of an ether.

EFFECT: method enables selective production of various types of fluorine-containing compounds without any inhibition with high output, without using phosgene and without obtaining hydrogen chloride as a by-product.

10 cl, 13 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing a carbonate compound, involving reaction of a compound of formula , wherein each of X1-X6 represents a chlorine atom, with a compound having one OH group, or a compound having two or more OH groups, in the presence of a catalyst, the catalyst containing a halogen salt.

EFFECT: invention is meant for selective production of various types of carbonate compounds without any inhibition of high output, without using phosgene and without obtaining hydrogen chloride as a by-product.

12 cl, 18 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing diaryl carbonate and processing at least a portion of the resultant solution which contains an alkali metal chloride in an alkali metal chloride electrolysis cell down the process chain, which involves the following steps: a) obtaining phosgene by reacting chlorine with carbon monoxide, b) reacting phosgene formed at step a) with at least one monophenol in the presence of a base, optionally a base catalyst, to diarylcarbonate and a solution which contains an alkali metal chloride, c) separating the organic phase which contains the diaryl carbonate formed at step b) and at least one-time washing of the organic phase containing diaryl carbonate, d) separating the solution which contains the alkali metal chloride remaining in accordance with step c) from solvent residue and, optionally, catalyst residue by stripping the solution with water vapour and treating with adsorbents, e) electrochemical oxidation of at least a portion of the solution which contains an alkali metal chloride from step d) to form chlorine, an alkali and, optionally, hydrogen, where during separation d) of the solution before treatment with adsorbents, the pH of the solution is set below or equal to 8 and f) at least a portion of the chlorine obtained according to step e) is returned to producing phosgene according to step a) and/or g) at least a portion of the obtained alkali solution obtained according to step e) is returned to producing diaryl carbonate according to step b).

EFFECT: method enables to obtain an end product with high purity and high output while cutting environmental contamination and solving the problem of waste water.

20 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a reactor for producing alkylene glycol, which is used as a starting substance in production of fibre, polyethylene terephthalate plastics and resins, and is also included in car antifreeze liquids from ethylene oxide, and a method of producing alkylene glycol using said reactor. The disclosed reactor has: (a) a carboxylation zone having one or more inlet openings for liquid reagents which contain alkylene oxide, water, a homogeneous carboxylation catalyst and a homogeneous hydrolysis catalyst, one or more inlet openings for carbon dioxide, one or more ejectors for mixing carbon dioxide with liquid reagents, and one or more outlet openings for the reaction solution which contains alkylene carbonate, water, the homogeneous carboxylation catalyst and the homogeneous hydrolysis catalyst; (b) a hydrolysis zone, having one or more inlet openings for the reaction solution, one or more outlet openings for carbon dioxide, and one or more outlet openings for the product solution which contains alkylene glycol, the homogeneous carboxylation catalyst and the homogeneous hydrolysis catalyst; and (c) a channel through which carbon dioxide can be fed from the hydrolysis zone into the carboxylation zone, where carboxylation zone and the hydrolysis zone are located in one reaction vessel, and where the carboxylation zone is separated from the hydrolysis zone by an inner partition.

EFFECT: objects enable to obtain the end product with high selectivity.

16 cl, 3 ex, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing an aromatic carbonate from a dialkylcarbonate, which involves reaction of an aromatic hydroxyl compound with a dialkylcarbonate in the presence of at least one type of samarium catalyst of formula 1 - SmX3 or formula 2 , where X is a C1-C10 alkoxy group, alkylphenoxy or phenoxy, where R1 and R2 are independently hydrogen and a C1-C6 alkyl group, respectively.

EFFECT: stability and high output.

6 cl, 1 dwg, 8 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing diaryl carbonate via re-esterification of an aromatic alcohol with dialkyl carbonate in the presence of a re-esterification catalyst over a time [ta], wherein the aryl group is selected from an unsubstituted phenyl and mono-, di- and trisubstituted phenyl group, wherein the alkyl group is selected from C2-C4 linear and branched alkyl groups, wherein concentration of the catalyst is denoted by [ca], which is expressed as the ratio of a gram of the catalyst per gram of the aromatic alcohol and dialkyl carbonate, wherein a period of time [tm] and concentration of the catalyst [ca] are defined with given approximation to equilibrium for re-esterification of the aromatic alcohol with dimethyl carbonate to obtain methyl aryl carbonate and methanol, wherein the product [ca]*ta is at least equal to 1.5*[cm]*tm, in, apart from that, the same reaction conditions and wherein the given approximation to equilibrium for re-esterification of the aromatic alcohol with dimethyl carbonate to obtain methyl aryl carbonate and methanol lies in the range from 70 to 100%.

EFFECT: method enables to obtain higher conversion of the aromatic alcohol.

13 cl, 1 dwg, 3 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 1,2-alkylene carbonate and versions of the method of producing 1,2-alkylene diol and dialkylcarbonate using the obtained 1,2-alkylene carbonate. The method producing 1,2-alkylene carbonate involves (i) contacting carbon dioxide, 1,2-alkylene oxide and a carbonisation catalyst in a reactor to form a crude stream which flows from the reactor and contains carbon dioxide, light components, 1,2-alkylene carbonate and the catalyst; (ii) separating carbon dioxide and light components from the crude stream flowing from the reactor to form a lower stream containing 1,2-alkylene carbonate and catalyst; (iii) distilling the lower stream formed at step (ii) to obtain a first distillation upper stream containing 1,2-alkylene carbonate and light components and a first distillation lower stream containing a catalyst, and recycling at least a portion of the first distillation lower stream into the reactor and (iv) distilling the first distillation upper stream to form a second distillation upper stream containing light components and a second distillation lower stream containing 1,2-alkylene carbonate, and recycling at least a portion of the second distillation upper stream into the reactor.

EFFECT: method enables to obtain 1,2-alkylene carbonate which does not contain or almost does not contain impurities.

16 cl, 2 ex 1 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel omega-3 lipid compounds of general formula (I) or to their pharmaceutically acceptable salt, where in formula (I): R1 and R2 are similar or different and can be selected from group of substitutes, consisting of hydrogen atom, hydroxy group, C1-C7alkyl group, halogen atom, C1-C7alkoxy group, C1-C7alkylthio group, C1-C7alkoxycarbonyl group, carboxy group, aminogroup and C1-C7alkylamino group; X represents carboxylic acid or its carbonate, selected from ethylcarboxylate, methylcarboxylate, n-propylcarboxylate, isopropylcarboxylate, n-butylcarboxylate, sec-butylcarboxylate or n-hexylcarboxylate, carboxylic acid in form of triglyceride, diglyceride, 1-monoglyceride or 2-monoglyceride, or carboxamide, selected from primary carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, N-ethylcarboxamide or N,N-diethylcarboxamide; and Y stands for C16-C22 alkene with two or more double bonds, which have E- and/or Z-configuration.

EFFECT: described are pharmaceutical and lipid compositions, which contain said compounds, for application as medications, in particular, for treatment and/or prevention of peripheral insulin resistance and/or condition of diabetes, for instance, type 2 diabetes, increased levels of triglycerides and/or levels of non-HDL cholesterol, LDL cholesterol and VLDL cholesterol, hyperlipidemic condition, for instance, hypertriglyceridemia (HTG), obesity or condition of excessive body weight, fatty liver disease, for instance, non-alcoholic fatty liver disease (NAFLD) or inflammatory disease or condition.

60 cl, 3 tbl, 65 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new lipid compound of general formula , wherein n=0; R1 and R2 are identical or different, and may be specified in a group of substitutes consisting of a hydrogen atom, a C1-C7alkyl group, a halogen atom and a C1-C7alkoxy group; X represents COR3 or CH2OR4, wherein R3 is specified in a group consisting of hydrogen, hydroxy, C1-C7alkoxy and amino; and R4 is specified in a group consisting of hydrogen, C1-C7alkyl or C1-C7acyl, Y represents C9-C21 alkene with one or more double bonds in E- or Z-configurations with the chain Y being unsubstituted and containing a double bond in the ω-3 position; provided R1 and R2 cannot simultaneously represent a hydrogen atom.

EFFECT: invention refers to pharmaceutical compositions containing the lipid compounds which are used for treating and/or preventing the conditions related to high NFkB functions, treating and/or preventing an inflammatory disease or a condition, lower plasma insulin and/or blood glucose levels, treating insulin resistance, treating and/or preventing peripheral tissue insulin resistance and/or diabetic condition, eg type 2 diabetes mellitus.

45 cl, 1 tbl, 1 dwg, 31 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula (I) where X is carboxylic acid, carboxylates, carboxylic anhydride, diglyceride, triglyceride, phospholipid, or carboxamides, or to any their pharmaceutically acceptable salt. The invention particularly refers to (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)-ethyl 2-ethyldocosa-4,7,10,13,16,19-hexanoate. The invention also refers to a food lipid composition and to a composition for diabetes, for reducing insulin, blood glucose, plasma triglyceride, for dislipidemia, for reducing blood cholesterol, body weight and for peripheral insulin resistance, including such compounds. Besides, the invention refers to methods for treating and/or preventing diabetes, dislipidemia, peripheral insulin resistance, body weight reduction and/or weight gain prevention, insulin, blood cholesterol, blood glucose and/or plasma triglyceride reduction.

EFFECT: higher clinical effectiveness.

61 cl, 4 tbl, 16 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to application of compounds with formula R2=R1-X, where R1 and R2 have 23 to 35 carbon atoms in sum, X represents primary alcohol functional group -CH2OH or carboxyl group -COOH, R1 is saturated linear hydrocarbon chain with 9 carbon atoms, and R2 is linear hydrocarbon chain, which is saturated or unsaturated, including 1 to 4 unsaturated double links.

EFFECT: producing formulations suited for application to hypercholesterolemia therapy and prophylaxis.

3 cl, 4 tbl, 6 ex

FIELD: organic chemistry, labeled compounds.

SUBSTANCE: invention relates to new tritium-labeled 2-arachidonoyl-[1,3-3H]-glycerol of the formula: CH3-(CH2)4-(CH=CHCH2)4-(CH2)2-COOCH-(C3HHOH)2 able to bind and activate cannabinoid receptors. This compound can be used in analytical, bioorganic chemistry, biochemistry and applied medicine.

EFFECT: valuable properties of compound.

1 ex

The invention relates to new compounds with the structure associated 1,3-propane diol, having the ability to penetrate lipid barriers, formula 1, where R1denotes an acyl group or a group of fatty alcohol, derived from C12-30preferably C16-30the fatty acids preferably with two or more double bonds in the CIS - or TRANS-position, and R2denotes hydrogen, acyl group or the group of fatty alcohol, which is the same or different from that specified for R1or is a biologically active residue that is different from the rest of Niacin, the chemical structure of which allows you to connect with 1,3-propane diol through the available carboxyl, alcohol or amino group

The invention relates to organic chemistry, in particular, to a method for producing 2,6-dimethyl-10-methylene-4-C1-C4arcoxia - bonil-2,6,11-dodecatrien

FIELD: organic chemistry, perfumery.

SUBSTANCE: invention relates to an aromatizing composition containing at least compound of the formula (I): as an active component wherein values w, m, P, X, G, Q and n are given in claim 1 of the invention description, and one or more aromatizing component. Also, invention relates to a method for improving, enhancing or modifying odor, to a method for aromatizing surface, method for enhancing or prolonging the diffusion effect of component on surface and to novel compounds of the formula (I) with exception of compounds enumerated in claim 10 of the invention description and to invention relating to aromatizing article using compounds of the formula (I).

EFFECT: valuable cosmetic properties of compounds.

13 cl, 14 ex

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