The method of producing binarydigit
(57) Abstract:The invention relates to a method of transforming bonarparte ormula I binarydigit formula II
< / BR>which is a known intermediate compound in the synthesis of progesterone. The method is carried out by oxidation of I with sodium hypochlorite in the presence of catalytic amount of 4-substituted derivative of 2,2,6,6-tetramethylpiperidine-1-oxyl in the presence of sodium bicarbonate and potassium bromide at pH of 8.5 to 10.5 at a temperature of from -10 to 15oC and with the stoichiometric quantity of sodium hypochlorite. The method allows to achieve high selectivity and allows to carry out the process continuously. 15 C.p. f-crystals. The invention relates to a method of transforming bonarparte formula I in binarydigit formula II, which is a known intermediate compound in the synthesis of progesterone.Oxidation of bonarparte (I) in binarydigit (II) is a well-known process.Famous is 4-hydroxy-TAMRA (4-hydroxy-2,2,6,6 - tetramethylpiperidine-1-oxyl), see Synthesis, 190-202 and L-414 (1971).In the journal J. Org. Chem., v. 52, 2559 (1987) described a two-phase oxidation of primary alcohols and secondary alcohols to aldehydes one-1-oxyl, with the use of bromide of potassium and 0.35 M solution of sodium hypochlorite at a pH of 8.5, supported buffer solution of sodium bicarbonate.In the journal J. Org. Chem., v. 56, 6110 (1991) described the use of stoichiometric quantities oxammonium salts generated during the processing of TEMPO (2,2,6,6-tetramethylpiperidine-1 - oxyl or 4-acetylamino-TAMRA (4-acetylamino-2,2,6,6 - tetramethylpiperidine-1-oxyl) organic sulfonic acids, for selective oxidation of primary alcohols and secondary alcohols to aldehydes or ketones, respectively.In the journal J. Amer. Chem. Soc., v. 106, 3374 (1984) described the use of TEMPO (2,2,6,6-Tetra-methylpiperidin-1 - oxyl or 4-hydroxy-TAMRA (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) for the catalytic oxidation of primary alcohols and secondary alcohols to aldehydes or ketones, respectively, oxygen and salts of divalent copper.In U.S. patent N 5136102 described using TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl or 4-substituted derivatives of TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and promesapanama salt for catalytic oxidation of secondary alcohols to ketones nitric acid and oxygen.In U.S. patent N 5155278 described using TEMPO (2,2,6,6-tetramethylene primary alcohols to aldehydes under the influence of nitric acid and oxygen.In U.S. patent N 5155279 described using TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl or 4-substituted derivatives of TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) for the catalytic selective oxidation of primary alcohols to aldehydes under the influence of nitric acid in the absence of oxygen.In U.S. patent N 5155280 described using TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl or 4-substituted derivatives of TEMPO (2,2,6, 6-tetramethylpiperidine-1-oxyl) and nitrosodialkylamines salt of an alkali metal for the catalytic selective oxidation of primary alcohols to aldehydes by the action of oxygen in the absence of nitric acid.In the Japan patent N J5 6152498 described the oxidation of bonarparte in binarydigit using dimethyl sulfide and N-chlorosuccinimide or chlorine.Described is a method of obtaining binarydigit formula II
< / BR>which includes: 1) formation of a mixture of (a) bonarparte formula I
< / BR>b) a catalytic amount of 4-hydroxy-2,2,6,6 - tetramethylpiperidine-1-oxyl in the range of pH from about 8.5 to about 10.5 and at a temperature range of approximately -10 to approximately 15oC and (2) contacting the mixture of stage (1) with the stoichiometric quantity of hypochlorite (see diagram A is use progesterone and hydrocortisone, see journal, J. Amer. Chem. Soc., v. 74, 5933 (1952).The present invention is accomplished by 1) formation of a mixture of bonarparte (I), catalytic amount of 4-hydroxy - TAMRA (2,2,6,6-tetramethylpiperidine-1-oxyl) in the range of pH from about 8.5 to about 10.5 and at a temperature range of about -10 to 15oC and 2) contacting the mixture of stage (1) with the stoichiometric quantity of hypochlorite. Preferably this reaction is carried out in the presence of bromide, preferably a catalytic amount of bromide. This mixture may be cooled at any time before adding the hypochlorite.The current (effective) number of 4-hydroxy-2,2,6,6 - tetramethylpiperidine-1-oxyl range from approximately 0.025 mol.% up to about 15 mol.%; preferably, the number of 4-hydroxy - 2,2,6,6-tetramethylpiperidine-1-oxyl ranged from approximately 0.025 mol.% up to about 2.5 mol.%. An effective amount of bromide is from about 5 mol.% up to about 25 mol.%; preferably, the amount of bromide ranged from about 10 mol.% up to about 15 mol. %. The pH preferably is regulated through the use of bicarbonate. An effective amount of bicarbonate is from about 5 mol.% up to about 30 mol.%; p is a or bicarbonate is not essential, while these salts are soluble; the preferred cations are sodium, potassium and lithium, the preferred sodium or potassium. Effective solvents include dichloromethane, toluene, ethyl acetate, methyl tert-butyl ether, dichloromethane, o-dichlorobenzene, chlorobenzene and chloroform. The preferred solvent is methylene chloride. Although effective solvents are organic solvents which are not miscible with water, a small amount of water is effective and even preferred, as is well known to specialists in this field. In addition, the hypochlorite is added to the aqueous mixture. Preferably, the reaction temperature was in the range of from about -5oC to about 5oC. Preferably, the hypochlorite was added over a period of time from about 1 hour to about 6 hours Preferably, the amount of hypochlorite ranged from about 95 mol.% to about 120 mol. %. Preferably, after stage 2), the reaction mixture was rapidly cooled. Efficient coolers include bisulfite, thiosulfate, dimethyldisulfide, trimethylphosphate and triethyl phosphate. Preferably, the cooler was sodium thiosulfate or potassium.How is ecialists in this area.The reaction mixture is treated by methods known to experts in this field.Binarydigit (II) can be converted into progesterone known methods, see journal, J. C. S. Chem. Comm., 314 (1969) and Tet. Lett., 985 (1969).The following definitions and explanations are given for terms used throughout the volume of the document, including the description and the claims.4-Hydroxy-TEMRO relates to 4-hydroxy-2,2,6,6 - tetramethylpiperidine-1-oxyl; TEMPO - 2,2,6,6-tetramethylpiperidine-1-oxyl.It is assumed that no additional development, any specialist in this field will be able to fully implement the present invention, using the preceding description. The following detailed examples describe the preparation of various substances and/or performing the various processes of the invention, and they should be considered as merely illustrative and not limiting the preceding description in any way. Specialists in this field will be able to easily recognize the corresponding change techniques both in terms of reagents, and reaction conditions and techniques.Example 1. Turning bonarparte (I) in binarydigit (II) if 1oC 4-Gidda potassium, 133 mg of sodium bicarbonate, 14 ml of dichloromethane and 2.2 ml of water is cooled to 1oC. Maintaining this temperature, add 6.3 ml of aqueous 14% solution of sodium hypochlorite for 5 hours the Reaction is finished, and add an aqueous solution of sodium thiosulfate, share two phases, and the product - binarydigit crystallizes when replacing dichloromethane in heptane. Get the desired compound with a melting point 153-154oC.An NMR spectrum (CDCl3) : 9,56, 5,73, 2,2-2,5, 1,2-2,1, 1,20, 1,10, 0,79.2D2= +of 83.4oC (methylene chloride, C = 1).Example 2. Turning bonarparte (I) in binarydigit (II) if 10oC with 4-hydroxy-TAMRA.Following the General method of example 1 and making non-critical changes to the method of example 1 is repeated with 10oC and get the desired connection.Example 3. Turning bonarparte (I) in binarydigit (II) at -10oC with 4-hydroxy-TAMRA.Following the General method of example 1 and making non-critical changes to the method of example 1 is repeated with -10oC and get the desired connection.Example 4. Turning bonarparte (I) in binarydigit (II) if 1oC with 4-hydroxy-TAMRA.Following the General methodology of parameterdependent-1-oxyl, and get the desired connection.Example 5. Turning bonarparte (I) in binarydigit (II) if 1oC with 4-hydroxy-TAMRA.Following the General method of example 1 and making non-critical changes to the method of example 1 is repeated, using 5 mg of 4-hydroxy - 2,2,6,6-tetramethylpiperidine-1-oxyl, and receive the requested connection.Example 6. Turning bonarparte (I) in binarydigit (II) with 4-oxo-TAMRA.A mixture of 6.6 g of bonarparte (I), 18 mg of 4-oxo-2,2,6,6 - tetramethylpiperidine-1-oxyl, 238 mg of potassium bromide, 180 mg of sodium bicarbonate, 30 ml of dichloromethane and 5 ml of water is cooled to 1oC. Then, to this mixture of 11.4 ml of water 14,6% sodium hypochlorite solution for 15 minutes At this reaction get the desired connection, but conversion of bonarparte is only 7% with selectivity to binarydigit 58%. 1. The method of producing binarydigit formula II
< / BR>including the oxidation of bonarparte formula I
< / BR>the hypochlorite in the presence of catalytic amount of 4-substituted derivative-2,2,6,6-tetramethylpiperidine-1-oxyl in the presence of bicarbonate and potassium bromide, characterized in that the contacting of a mixture of bonarparte and catalytic coricedin-1-oxyl is carried out at pH 8.5 - the 10.5 at a temperature of from -10 to 15oAnd with the stoichiometric quantity of hypochlorite.2. The method according to p. 1, characterized in that a catalytic amount of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl is 0.025 to 15.0 mol.%.3. The method according to p. 1, characterized in that kataliticheskoe the number of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl is 0.025 to 2.5 mol.%.4. The method according to any of paragraphs.1 to 3, characterized in that the potassium bromide is used in catalytic amounts.5. The method according to p. 4, characterized in that a catalytic amount of potassium bromide is 5 to 25 mol.%.6. The method according to p. 5, characterized in that a catalytic amount of bromide of potassium is 10 - 15 mol.%.7. The method according to any of paragraphs.1 - 6, characterized in that the amount of bicarbonate is 5 to 30 mol.%.8. The method according to p. 7, characterized in that the amount of bicarbonate is 10 to 20 mol.%.9. The method according to any of paragraphs.4 to 6, 7 and 8, characterized in that userpart formula I, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, bromide of potassium, and bicarbonate are all mixed together and then cooled to a temperature of from -10 to 15oC.10. The method according to any of paragraphs.1 to 9, characterized testilomake ether, dichloromethane, o-dichlorobenzene, chlorobenzene and chloroform.11. The method according to p. 10, wherein the solvent is methylene chloride.12. The method according to any of paragraphs.1 - 11, characterized in that the temperature is from -5 to 5oC.13. The method according to any of paragraphs.1 - 12, characterized in that the amount of hypochlorite is 95 - 120 mol.%.14. The method according to any of paragraphs.1 - 12, characterized in that the reaction mixture is cooled rapidly after contacting this mixture with hypochlorite.15. The method according to p. 14, characterized in that the reaction mixture is cooled chiller selected from bisulfite, thiosulfate, dimethyl sulfide, trimethyl phosphate and triethyl phosphate.16. The method according to p. 15, characterized in that the cooler is sodium thiosulfate or potassium.
an intermediate product in the synthesis of natural phytohormone of epibrassinolide with high growth promoting activity (1-3)
which is an intermediate substance to obtain (22R, 23R)-3- acetoxy-22,23-isopropylidenedioxy-24-metalholic-5 - ene of formula II;
Compound II is a well-known synthetic precursor hormone brassinolide) III, which is found in very low concentrations in some plants and is the most active of the new class of natural hormones - steroids, and therefore can be used in agriculture as a growth promoter, plant /1/
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
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
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
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
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
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