Method of producing 2,3-monoacetonide 20-hydroxyecdysone

FIELD: chemistry.

SUBSTANCE: invention refers to synthesis of biologically active substances, in particular specifically, to improved method of producing 2,3-monoacetonide 20-hydroxyecdysone of formula found in very small amounts in some plants, e.g. Rhaponticum carthamoides. Method is implemented by interaction of 20- hydroxyecdysone (1.0 g, 2.08 mmole) and acetone with phosphomolybdic acid (PMA) added. As suspension is effected by mother compound in PMA acetone (0.3 g, 0.16 mmole), after 5 min homogenisation of reaction mixture is observed to be steamed by neutralisation with 0.1% sodium hydrocarbonate solution with following ethyl acetate and chromatography extraction of the end product, thus resulting in isolation of the end 2,3-monoacetonide 20- hydroxyecdysone of 32% yield.

EFFECT: method is highly selective and single-stage.

2 cl, 1 ex

 

The invention relates to the synthesis of biologically active substances, in particular to the synthesis of ecdysteroids, specifically to the synthesis of 2,3-monoacetate 20-hydroxyecdysone (I).

2,3-Monoacetyl I in very small amounts present in some plant species, for example Rhaponticum carthamoides. [Ecdysteroids of the root bark of Vitex caescens. // Phytochemistry, 1997, 45, No. 6, 1149-1152].

Ecdysteroids are widely distributed in the animal and vegetable world and function as regulators of molting and metamorphosis insects and crustaceans. Being non-toxic to mammals, these compounds and their analogues are of interest to medicine.

As derived 20-hydroxyecdysone (II)selectively protected 2,3-hydroxyl groups, 2,3-monoclonal (I) convenient for subsequent selective transformation of one of the most representative of phytoecdysteroids II rare in nature ecdysteroids. For example, in the synthesis of SIDACTION 2,3-monoacetyl I got through three-stage transformations 20-hydroxyecdysone II [1] [Roussel P.G., Turner N.J., Dinan L.N. Synthesis of Shidasdterone and the Unambiguous Determination of its Configuration at C-22. // J. Chem. Soc., Chem. Commun., 1995, 933-934]. When interacting 20-hydroxyecdysone II with phenylboric acid in dimethylformamide (DMF) was obtained 20,22-phenylboronic 20-hydroxyecdysone (III). When interacting III 2,2-dimethoxypropane and TsOH in acetone floor is Chen 2,3-acetonide-20,22-phenylboronic 20-hydroxyecdysone (IV). Processing IV 30%hydrogen peroxide solution in the presence of NaOH in tetrahydrofuran led to selective removal boronates protection and to obtain 2,3-monoacetate I, the total yield of which was 65% (scheme 1).

Scheme 1.

The disadvantages of this method are multi-stage, the use of specific and expensive reagents, incomplete conversion of the starting compounds at each stage, which requires additional purification of the intermediate and final products.

The task of the invention is a simplified method of producing 2,3-monoacetate 20-hydroxyecdysone.

A distinctive feature of the proposed method, which allows to solve the problem, is the use of phosphorus molybdenum acid in the reaction 20-hydroxyecdysone II with acetone, followed by separation of the resulting product column chromatography.

Very attractive is the possibility of obtaining compounds I by reacting 20-hydroxyecdysone II with acetone in the presence of acid. However, according to a known method [2] [Odinokov V.N., Galiautdinov IV, Nedopekin D.V., Khalilov L.M. Triptoreline and dehydration of the acetonide 20-hydroxyecdysone. Synthesis of thestereo Century, " Izv. An. Ser. Chem. - 2003. No. 1. - S-224] the reaction of II with acetone in the presence the AI 0.1 mol.% phosphorus molybdenum acid (PMK) leads to a mixture (85:15) 2,3:20,22-diacetonide (V) and 20,22-monoacetate 20-hydroxyecdysone (VI):

Scheme 2.

When studying the interaction of 20-hydroxyecdysone II with acetone in the presence of PMK found that the interaction of a suspension of compound (II) and 7-8 mol. % PMK in acetone after 5 min was observed homogenization and appeared green color of the reaction mixture. Its evaporation, neutralization of 0.1% solution of sodium bicarbonate, followed by extraction of the target product by ethyl acetate and chromatographytandem was obtained 2,3-monoacetyl, identical (IR, UV, NMR1H and13C) 2,3-monoacetyl previously described in the above-mentioned 3-stage synthesis [1].

Scheme 3.

The undoubted advantage of the proposed synthesis is a single-stage process process and availability of reagents, which greatly simplifies the method of obtaining the target product.

An example of the method. To a suspension of 1.0 g (2.08 mmol) in 200 ml of acetone was added 0.3 g (0.16 mmol, 7.7 mol.%) phosphorus molybdenum acid. The reaction mass was stirred at room temperature until the reaction mixture becomes homogeneous and get a greenish color (~5 min). The reaction mixture was evaporated to a volume of ~25 ml, was added 15 ml of a 0.1% solution of NaHCO3and were extracted with ethyl acetate (100 ml × 3). The extract was evaporated and chromatographically on a column of 40 g of SiO2(eluent - CHCl3-M IS HE, 9:1)with 0.35 g (32%) of compound I, TPL 135-137°C, [α]D20+29.6° (C=2.53, Meon), IR, UV, NMR1H and13With identical to those given in the literature [1].

In addition to the target compound I from the total reaction product were selected diacetone V (yield 30%, TPL 134-135°C, [α]D20+39.0° (C=1.1, CHCl3)) and 20,22-monoacetyl VI (yield 38%, TPL p.223-224°C, [α]D20+58.0° (C=0.9, CHCl3)).

The way to obtain 2,3-monoacetate 20-hydroxyecdysone formula I

of 20-hydroxyecdysone but also characterized in that 20-hydroxyecdysone is subjected to interaction with acetone in the presence of 7.7 mol.% phosphorus molybdenum acid to the homogenization of the reaction mixture and the appearance of the green color of the solution at room temperature for 5 min, followed by separation of the target product known techniques.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: claimed invention describes paroxetine cholate or salt of cholic acid derivative and composition, which contains paroxetine and cholic acid or its derivative. Also described is pharmaceutical composition for treatment of depressive states, containing paroxetine salt or composition. Pharmaceutical composition can be part of peroral medication, swallowed without water, on form of disintegrating in mouth paroxetine tablet.

EFFECT: obtaining paroxetine cholate or salt of cholic acid derivative, which can be used in pharmacology.

19 cl, 38 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: polyaminosteroid branched derivatives of general formula I are described, where R1 is saturated or unsaturated C2-C10alkyl (conjugated or branched) or methyl, R2 is COOH or branched polyamine fragments, R3 is H, OR19, where R19 is H or C1-6acyl, R4 is H, R5 is H, CH3, R6 is H, CH3, R7=R8=R9=H, R10 is H, CH3, R11 is OH,-OSO3, - O-acyl, -(Z)n-(NR-Z)p-N(R)2, Z is linear hydrocarbon diradical, n=0, 1, p=1, R-H, C1-6alkyl, C1-6aminoalkyl, possibly substituted by C1-6alkyl, R12=R13=R15=H, R16 is H, OH, R17 is H, R18 is H, CH3, possible double bond. Compounds possess bactericidal activity and can be used for prevention of bacterial infections.

EFFECT: production of polyaminosteroid derivatives, possessing bactericidal activity which can be used for prevention of bacterial infections.

27 cl, 31 ex, 1 tbl, 2 dwg

FIELD: medicinal industry, sterols.

SUBSTANCE: invention relates, in particular, to the improved method for producing sterols - lanosterol and cholesterol from wooly fat that can be used in preparing medicinal and cosmetic preparations. Method is carried out by alkaline hydrolysis of raw, extraction of unsaponifiable substances, removal of solvent and successive isolation of lanosterol and cholesterol. Alkaline hydrolysis of raw is carried out with a mixture of ethanol, sodium hydroxide, pyrogallol and water at temperature 70°C for 4 h at stirring in the following ratio of components: raw : ethanol : sodium hydroxide : pyrogallol : water = 100.0:(300.0-350.0):(30.0-35.0):(0.01-0.05):(7.5-12.0), respectively, with the indicated mixture with addition of toluene in the following ratio: raw : ethanol : sodium hydroxide : pyrogallol : toluene : water = 100.0:(220.0-255.0):(30.0-38.0):(0.05-0.12):(100.0-137.0):(2.5-7.0), respectively, and lanosterol is isolated by precipitation from mixture of methylene chloride and ethanol in the ratio = 1:1. Before removal of solvent unsaponifiable substances are extracted at temperature 50°C for 2-3 h at stirring. Invention provides increasing yield of the end product, enhancing qualitative indices and reducing cost of production.

EFFECT: improved producing method.

2 cl, 3 ex

FIELD: organic chemistry, chemistry of steroids.

SUBSTANCE: invention relates to a new method for synthesis of 6β-formyl-B-norcholestane-3β,5β-diol of the formula (I): by constricting six-membered B-ring of cholesterol. Method involves photooxidation of cholesterol with air oxygen at irradiation by visible light in the presence of porphyrine photosensibilizing agent immobilized on low-molecular fraction of copolymer of tetrafluoroethylene and perfluoro-3,6-dioxo-5-methyl-6-sulfonylfluoride octene-1 in the mass ratio porphyrine photosensibilizing agent : cholesterol = 1:(12-15). As porphyrine photosensibilizing agent 5,10,15,20-tetraphenylporphyrine can be used. Method shows technological simplicity, it doesn't require rigid conditions and provides the high yield of the end product.

EFFECT: improved preparing method.

2 cl, 3 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention represents new derivatives of 17,20-dihydrofusidic acid of the formula (Ia)

wherein Q1 and Q2 are similar or different and mean -CO-, -CHOH-, -CHRO- wherein R means (C1-C4)-alkyl; Q3 means -CH2-; Y means hydrogen atom (H); A means -O- or -S-; R1 means (C1-C4)-alkyl, (C2-C4)-olefin, (C1-C6)-acyl, (C3-C7)-cycloalkylcarbonyl, benzoyl. These derivatives are used in pharmaceutical compositions for treatment of infectious diseases, in particular, in composition for topical applying for treatment of infectious diseases of skin and eyes.

EFFECT: valuable medicinal properties of compounds.

22 cl, 7 tbl, 41 ex

FIELD: organic chemistry, steroids, medicine, pharmacy.

SUBSTANCE: invention relates to 3-methylene-steroid derivative of the general formula (1):

wherein R1 means hydrogen atom (H), or in common with R3 it forms β-epoxide; or R1 is absent in the presence of 5-10-double bond; R2 means (C1-C5)-alkyl; R3 means βH, βCH3 or in common with R1 it forms β-epoxide; either R3 is absent in the presence of 5-10-double bond; R4 means hydrogen atom, lower alkyl; Y represents [H, H], [OH, H], [OH, (C2-C5)-alkenyl], [OH, (C2-C5)-alkynyl] or (C1-C6)-alkylidene, or =NOR5 wherein R5 means hydrogen atom (H), lower alkyl; dotted lines represent optional double bond. Compound can relate also to its prodrug used for treatment of arthritis and/or autoimmune diseases.

EFFECT: valuable medicinal properties of compounds, improved method for treatment.

38 cl, 1 tbl, 18 ex

The invention relates to substituted derivatives of propanolamine with bile acids of formula I and their pharmaceutically acceptable salts and physiologically functional derivatives, where GS is a group of the bile acid of the formula II, R1connection with X, HE, R2connection with X, HE, -O-(C1-C6)alkyl, -NH-(C2-C6)-alkyl-SO3N, -NH-(C1-C6)-alkyl-COOH, R1and R2at the same time does not mean the relationship with X, X -

l,m, n- 0,1; L - (C1-C6)-alkyl, AA1, AA2independently amino acid residue, may be one - or multi-substituted amino group

The invention relates to substituted phenylalkylamines, their pharmaceutically acceptable salts and physiologically functional derivatives

The invention relates to an improved method of direct esterification of Stanlow/sterols interaction of stanol/sterols and acid taken in stoichiometric ratio, in the presence of a sufficient amount of catalyst, which can be acidic or basic, and in the presence of a sufficient amount of decolorizing agent, preferably activated carbon

FIELD: organic chemistry, steroids, medicine, pharmacy.

SUBSTANCE: invention relates to 3-methylene-steroid derivative of the general formula (1):

wherein R1 means hydrogen atom (H), or in common with R3 it forms β-epoxide; or R1 is absent in the presence of 5-10-double bond; R2 means (C1-C5)-alkyl; R3 means βH, βCH3 or in common with R1 it forms β-epoxide; either R3 is absent in the presence of 5-10-double bond; R4 means hydrogen atom, lower alkyl; Y represents [H, H], [OH, H], [OH, (C2-C5)-alkenyl], [OH, (C2-C5)-alkynyl] or (C1-C6)-alkylidene, or =NOR5 wherein R5 means hydrogen atom (H), lower alkyl; dotted lines represent optional double bond. Compound can relate also to its prodrug used for treatment of arthritis and/or autoimmune diseases.

EFFECT: valuable medicinal properties of compounds, improved method for treatment.

38 cl, 1 tbl, 18 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention represents new derivatives of 17,20-dihydrofusidic acid of the formula (Ia)

wherein Q1 and Q2 are similar or different and mean -CO-, -CHOH-, -CHRO- wherein R means (C1-C4)-alkyl; Q3 means -CH2-; Y means hydrogen atom (H); A means -O- or -S-; R1 means (C1-C4)-alkyl, (C2-C4)-olefin, (C1-C6)-acyl, (C3-C7)-cycloalkylcarbonyl, benzoyl. These derivatives are used in pharmaceutical compositions for treatment of infectious diseases, in particular, in composition for topical applying for treatment of infectious diseases of skin and eyes.

EFFECT: valuable medicinal properties of compounds.

22 cl, 7 tbl, 41 ex

FIELD: organic chemistry, chemistry of steroids.

SUBSTANCE: invention relates to a new method for synthesis of 6β-formyl-B-norcholestane-3β,5β-diol of the formula (I): by constricting six-membered B-ring of cholesterol. Method involves photooxidation of cholesterol with air oxygen at irradiation by visible light in the presence of porphyrine photosensibilizing agent immobilized on low-molecular fraction of copolymer of tetrafluoroethylene and perfluoro-3,6-dioxo-5-methyl-6-sulfonylfluoride octene-1 in the mass ratio porphyrine photosensibilizing agent : cholesterol = 1:(12-15). As porphyrine photosensibilizing agent 5,10,15,20-tetraphenylporphyrine can be used. Method shows technological simplicity, it doesn't require rigid conditions and provides the high yield of the end product.

EFFECT: improved preparing method.

2 cl, 3 ex

FIELD: medicinal industry, sterols.

SUBSTANCE: invention relates, in particular, to the improved method for producing sterols - lanosterol and cholesterol from wooly fat that can be used in preparing medicinal and cosmetic preparations. Method is carried out by alkaline hydrolysis of raw, extraction of unsaponifiable substances, removal of solvent and successive isolation of lanosterol and cholesterol. Alkaline hydrolysis of raw is carried out with a mixture of ethanol, sodium hydroxide, pyrogallol and water at temperature 70°C for 4 h at stirring in the following ratio of components: raw : ethanol : sodium hydroxide : pyrogallol : water = 100.0:(300.0-350.0):(30.0-35.0):(0.01-0.05):(7.5-12.0), respectively, with the indicated mixture with addition of toluene in the following ratio: raw : ethanol : sodium hydroxide : pyrogallol : toluene : water = 100.0:(220.0-255.0):(30.0-38.0):(0.05-0.12):(100.0-137.0):(2.5-7.0), respectively, and lanosterol is isolated by precipitation from mixture of methylene chloride and ethanol in the ratio = 1:1. Before removal of solvent unsaponifiable substances are extracted at temperature 50°C for 2-3 h at stirring. Invention provides increasing yield of the end product, enhancing qualitative indices and reducing cost of production.

EFFECT: improved producing method.

2 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: polyaminosteroid branched derivatives of general formula I are described, where R1 is saturated or unsaturated C2-C10alkyl (conjugated or branched) or methyl, R2 is COOH or branched polyamine fragments, R3 is H, OR19, where R19 is H or C1-6acyl, R4 is H, R5 is H, CH3, R6 is H, CH3, R7=R8=R9=H, R10 is H, CH3, R11 is OH,-OSO3, - O-acyl, -(Z)n-(NR-Z)p-N(R)2, Z is linear hydrocarbon diradical, n=0, 1, p=1, R-H, C1-6alkyl, C1-6aminoalkyl, possibly substituted by C1-6alkyl, R12=R13=R15=H, R16 is H, OH, R17 is H, R18 is H, CH3, possible double bond. Compounds possess bactericidal activity and can be used for prevention of bacterial infections.

EFFECT: production of polyaminosteroid derivatives, possessing bactericidal activity which can be used for prevention of bacterial infections.

27 cl, 31 ex, 1 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: claimed invention describes paroxetine cholate or salt of cholic acid derivative and composition, which contains paroxetine and cholic acid or its derivative. Also described is pharmaceutical composition for treatment of depressive states, containing paroxetine salt or composition. Pharmaceutical composition can be part of peroral medication, swallowed without water, on form of disintegrating in mouth paroxetine tablet.

EFFECT: obtaining paroxetine cholate or salt of cholic acid derivative, which can be used in pharmacology.

19 cl, 38 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to synthesis of biologically active substances, in particular specifically, to improved method of producing 2,3-monoacetonide 20-hydroxyecdysone of formula found in very small amounts in some plants, e.g. Rhaponticum carthamoides. Method is implemented by interaction of 20- hydroxyecdysone (1.0 g, 2.08 mmole) and acetone with phosphomolybdic acid (PMA) added. As suspension is effected by mother compound in PMA acetone (0.3 g, 0.16 mmole), after 5 min homogenisation of reaction mixture is observed to be steamed by neutralisation with 0.1% sodium hydrocarbonate solution with following ethyl acetate and chromatography extraction of the end product, thus resulting in isolation of the end 2,3-monoacetonide 20- hydroxyecdysone of 32% yield.

EFFECT: method is highly selective and single-stage.

2 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel fusidic acid derivatives of general formula [I], where X represents halogen, trifluoromethyl, C1-C7alkyl, substituted with phenyl, C2-C9alkenyl, optionally substituted with C1-C7alkyl, halogen or phenyl, phenyl, optionally substituted with one or two similar or different substituents, selected from group consisting of halogen, C1-C7alkyl, C2-C9alkenyl, phenyl, C1-C6alkoxy, nitro, C1-C6alkyltio, trifluoromethyl and cyano; or X represents naphtyl; Y and Z both represent hydrogen or together with bond C-17/C-20 form double bond between C-17 and C-20 or together represent methylene and form cyclopropane ring in combination with C-17 and C-20; A represents O, S or S(O); B represents C1-6alkyl, C2-6alkenyl, C1-6acyl, phenyl or benzoyl, where C1-6alkyl is optionally substituted with one or more halogens, hydroxy, C2-6alkenyl, phenyl, C1-4heteroaryl or C1-6alkoxy; Q1 represents -(CHOH)-, or -(CHW)-, where W represents halogen or azido; Q2 represents -(CHOH)-; to their pharmaceutically acceptable salts and easily hydrolysed esters and to pharmaceutical compositions, including said derivatives, as well as to their application in therapy.

EFFECT: application in therapy.

31 cl, 127 ex, 5 tbl

FIELD: production processes.

SUBSTANCE: invention refers to wood working and wood chemical industries. Birch bark is broken down, mixed with liquid, the mixture is held at temperature higher than mixture freezing temperature, then triterpene compounds are separated from lingo-adipic residue with the following filtration and drying. Birch bark is additionally broken down by method of impact-abrasing and/or abrasing effect till obtaining birch bark flour. Birch bark flour is mixed with liquid with density of 0.999-0.958 kg/m3. Mixture is held for 0.1-10 hours and then separated by flotation to hydrophobic and hydrophilous fraction. Solution remaining after separation is condensed and dried. Obtained hydrophobic fraction - mixture of triterpene compounds - is exposed to recrystallisation in ethanol with activated charcoal and then betuline, solution of triterpene compounds in ethanol and mixture of triterpene and polyphenol compounds at carbon matrix is obtained. Or triterpene compounds mixture is separated to fractions in carbon-dioxide extractor and betuline, dry mixture of triterpene and polyphenol compounds are obtained. Hydrophilous fraction - lingo-adipic flour - is separated from liquid and dried out.

EFFECT: increase of environmental safety and method effectiveness.

6 cl, 4 ex, 3 dwg

FIELD: medicine.

SUBSTANCE: present invention presents a preparation to reduce insulin resistance. The preparation contains 3-O-v-D-glucopyranosyl-4-methylergost-7-ene-3-ole, or an extract made with using an organic solvent, or an extract made with using hot water, or a drained liquid of a plant of Liliaceae family, or fraction thereof which contains this compound as an active component.

EFFECT: production of the preparation which is suitable for inhibition of adipocytokine production, particularly adipocytokine which cause insulin resistance, and for prevention of pathological conditions caused by insulin resistance, or simplification of clinical course of said pathological conditions.

9 cl, 3 ex

Up!