The method of obtaining5-cyclo-24r-methyl - a-cholesterol-7,22-dien - 6-ola


(57) Abstract:

Usage: as an intermediate product in the synthesis of the phytohormone epibrassinolide. Essence: the product 3,5-cyclo-24-methyl-5-cholesterol-7,22-Dien-6-ol. The output 94% so pl. 95-96C. the Method speeds up the process, eliminates the need for purification of the target product. Reagent: 1: ergosterol. Reagent 2: methansulfonate. Reaction conditions: in the midst of pyridine, followed by treatment with sodium bicarbonate in aqueous acetone.

The invention relates to methods for the preparation of 3 , 5-cyclo-24 methyl-5-cholesta-7,22-Dien-6-ol of the formula (I), which is

an intermediate product in the synthesis of natural phytohormone of epibrassinolide with high growth promoting activity (1-3).

Known (4) the only method of obtaining 3-5-cyclo-24R-methyl - 5-cholesta, 7,22-Dien-6-ol (I) (prototype), which is that natural Sterol ergosterol (II) make toilet (III) the action of n-toluensulfonate in pyridine at room temperature during the day. Then toilet ergosterol (III) is subjected to the i-steroid rearrangement of 3-5-cyclo-24R-methyl-5-cholesta-7,22-Dien-6-ol (I) boiling in aqueous acetone in the presence of potassium bicarbonate for 5 minutes Total output Ciclopi is ergosterin (II), the need for treatment at both stages from the admixture of the compound (IV), and the duration of the process.

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The purpose of the invention is the increase of output 3 , 5-cyclo-24R-methyl-5-cholesta-7,22-Dien-6-ol (I) of ergosterol (II) and the reduction in the duration of the process.

This goal is achieved by the described method, which consists in the fact that ergosterol (II) processing methanesulfonamido in pyridine turn in mesilate (V), which by boiling in aqueous acetone in the presence of potassium bicarbonate programmirovaniya 3-5-cyclo-24R-methyl-5-cholesta-7,22-Dien-6-ol (I).

The method differs from the nearest known fact that in the i-steroid rearrangement instead tosilata ergosterol (III) is used mesilate (V).

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Known use for the i-steroid rearrangement nelfinavir 22-dehydrocholesterol (VI), containing in the loop. In only one double bond [5]. The output of the ketone (IX) in this case amounted to 79%.

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The use of nelfinavir instead tosilata does not in this case any benefits. Thus, the compound (XIII) obtained according to a similar pattern through the stage tosilata (XI) with yields of 80% (6). The application of the mesylates of sterols containing diene system in the cycle, q is retene is an example.

P R I m e R 1. Ergosterol (5 g, 1,210-2mol) is dissolved in 40 ml of pyridine and with continuous stirring, add 2,03 g (1,7710-2mol) methanesulfonamide. The reaction mixture was incubated for 15-20 min, then diluted with water and extracted with ether. The extract is washed with 20% acetic acid, then with water and saturated sodium bicarbonate solution. Dried over sodium sulfate, evaporated. Selected 5,88 g of compound IV. The yield of 98.2% So pl. 95-96aboutC. the infrared spectrum, cm-1; 1180, 1325 (O=S=D).

Range PMR (200 MHz , M. D.) to 0.62 (3H, 18-Me), of 0.82 (3H, I GC, 26/27 IU), 0,84 D. (3H, I GC, 26/27-IU) to 0.92 (3H, I GC, 24-IU), 0,96 C.

To a solution of 5.2 g nelfinavir IV in 700 ml of acetone is added a solution of 12 g of potassium bicarbonate in 100 ml of water. The reaction mixture is refluxed for 1-1,5 hours and Then evaporated about 1/3. diluted with 300 ml of water and extracted with ether. The extract is dried over sodium sulfate, evaporated. Selected 4,18 g Ciclosport I. the Yield of 96.2%. So pl. 131-133aboutC.

The infrared spectrum, cm-1: 3400 (OH).

Range PMR (200 MHz , M. D.); of 0.64 (3H, 18-Me) 0,826 d 3H, I GC, 26/27 IU), 0,846 D. (3H, I GC, 26/27 IU) to 0.92 (3H, 7.2 Hz, 24-IU) of 1.03 (3H, Hz, 21-Me), a 1.08 (3H, 19-Me) 3,42 DD (1H, I14.5 GHz, I21.2 Hz, C6-N, 5.2 m (2N, C22-H and C23N); 5,47 m (1) - Rev. and allows to increase the yield of the target compounds from 49 to 94%, to reduce the length of the process, and eliminates the need for purification of the target product.

METHOD for the preparation of 3, 5-CYCLO-24R-METHYL - 5-CHOLESTEROL-7,22-DIEN - 6-OL, including the interaction of ergosterol with sulphonylchloride in pyridine and boiling received alfaprostol in aqueous acetone in the presence of potassium bicarbonate, characterized in that, to reduce processing time and increase the yield of the target product, as sulphonylchloride use methansulfonate.


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which is an intermediate substance to obtain (22R, 23R)-3- acetoxy-22,23-isopropylidenedioxy-24-metalholic-5 - ene of formula II;

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The invention relates to bio-organic chemistry, namely to new chemical compounds - N-hydroxyl-containing phosphonates steroids of General formula I XO-H where X is the residue of the hydroxyl-containing steroid,

for example:

cholesterol (Chs)< / BR>
testosterone (TS)which can be used as source reagents for solid-phase synthesis of steroid derivatives of oligonucleotides and their analogues

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.

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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.

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9 cl, 3 ex