61 results about "4-Androstenedione" patented technology

The invention relates to a preparation method for progestin. 4-androstenedione is used as a raw material. The preparation method comprises the following steps: A, etherate is synthetized, wherein the 4-androstenedione and triethyl orthoformate perform an acid catalyzed reaction in organic solvents of dichloromethane, low-carbon alcohol and the like to obtain the etherate 3-ethoxy-androstane-3, 5-diolefin-17-ketone; B, a nitro substance is synthetized, wherein the etherate in the organic solvents and nitroethane perform 17-bit addition under the catalysis of ethylenediamine to obtain the nitro substance 3-ethoxy-20-nitro-pregnane-3, 5, 17 (20)-triene; and C, the progestin is synthetized, wherein the nitro substance is reduced by zinc powder in organic solvents of acetic acids, low-carbon alcohol and the like, acid hydrolysis is performed, so that semi-finished products of the progestin are obtained, the semi-finished products of the progestin are decolored and refined by alcohol and activated carbon to obtain the progestin, the content of HPLC is more than 99.5%, the melting point is 128-131 DEG C, and the total yield of synthetized weight is 83-87%. When the method disclosed by the invention is used for producing the progestin, the yield is high, the degree of purity is good, the quality is stable, the solvent recovering rate is high, and the method is economic and environment-friendly.

The invention provides a preparation method for hydroxylation of 11 alpha of an important intermediate of a steroidal hormone substance, and aims to solve the problems that the conversion rate is low and the environment is polluted when a microorganism is used for converting steroidal C11 alpha for hydroxylation in the prior art. The preparation method comprises the following steps: strain breeding, wherein a strain of ochratoxin or rhizopus nigricans is inoculated to a corresponding seed medium for cultivation; substrate emulsification, wherein a substrate selected from one of 17-alpha hydroxyl progesterone, 4-androstenedione or 16,17-alpha epoxy progesterone is subjected to emulsification treatment under the action of a surfactant; fermented cultivation, wherein the ochratoxin or rhizopus nigricans is inoculated to a fermented medium to be cultivated for a period of time, and then one of emulsion liquids of sterilized 17-alpha hydroxyl progesterone, 4-androstenedione or 16,17-alpha epoxy progesterone is added for performing continuous fermented cultivation; extracting a finished product. The method has the advantages of high conversion rate, little pollution, environmental protection, low pressure and the like.

The invention relates to a method for preparing progesterone. According to the method, 4-androstenedione is used as raw materials, and hydroxyl cyanation, dehydration, protection, hydrogenation and addition hydrolysis reaction are carried out in sequence, and the progesterone is obtained. The 4-androstenedione which has the price advantage is used as the raw materials, the reaction condition is easy to control, post-processing is easy, and yield is high.

The invention discloses a method for preparing dehydroepiandrosterone through a chemical-enzyme method. The method comprises that dehydroepiandrosterone is prepared from 4-androstenedione as an initial substrate orderly through a chemical method and a biological method. In preparation, the two reaction processes are optimized. In the chemical method-based 5-androstenedione preparation process, a reaction solution is added into an aqueous solution with sodium ascorbate and acetic acid so that reaction conditions are mild. In the second biological method-based dehydroepiandrosterone preparation process, a ketoreductase is used as a catalyst so that the product yield and purity are improved. In the whole reaction processes, use amounts of a coenzyme and potassium tert-butoxide are low and a high practical value is obtained.

The invention relates to a high-yield simple preparation method of 17alpha-hydroxy progesterone. With 4-androstenedione as an initial raw material, the method comprises the following steps: performing a cyanogen alcoholization addition reaction between the 17-site carbonyl of 4-androstenedione and acetone hydrogen alcohol to obtain 17-alpha hydroxyl-17-beta cyanoandrostane-4-ene-3-one; performing a ketal protection reaction of the C3-site carbonyl to obtain a ketal product; and performing a direct methylation reaction between the ketal product and zinc chloride methane, and hydrolyzing to obtain 17alpha-hydroxy progesterone. The method provided by the invention has the advantages of short process, high yield, high product purity, mild reaction conditions, low cost and low energy consumption and is particularly suitable for industrial production.

The invention provides a preparation method of methyltestosterone. 4AD short for 4-androstenedione is taken as a raw material, and etherate is synthesized firstly as follows: 4AD and triethyl orthoformate are subjected to an acid catalyzed reaction in a low-carbon alcohol organic solvent, and 3-ethoxy-androst-3,5-diene-17-one as the etherate is obtained; then a Grignard product is synthesized as follows: a Grignard reagent methyl magnesium halide and the etherate are placed in an organic solvent, the 17-position ketone group of the etherate and the Grignard reagent are subjected to addition, and the Grignard product 3-ethoxy-17a-methyl-androst-3,5-diene-17-ol is obtained through hydrolysis; then the Grignard product is subjected to an acid catalyzed hydrolysis in an organic solvent, and crude methyltestosterone is obtained; the crude methyltestosterone is decolorized by activated carbon in C4-below low-carbon alcohol and recrystallized, the methyltestosterone is obtained, HPLC content is 99.0%-99.5%, and the total yield of synthesis weight is 75%-78%. According to the method, the raw materials are widely sourced, the process is simple and convenient to operate, the product yield is high, the purity is good, the solvent recovery rate is high in reaction and technological processing, and the method is economical and environment-friendly.

The invention discloses a method for preparing 19-demthyl-4-androstenedione, which comprises the steps of: based on estrone as a raw material, sequentially carrying out etherealization reaction, ketalation, Birch reducing reaction and hydrolysis reaction to obtain19-demethyl-4-androstenedione, wherein the reaction formula is shown in the specification. According to the method provided by the invention, the traditional phenolic group methyl etherealization process is improved, methyl carbonate replaces traditional high-toxicity carcinogenic etherealization reagents dimethyl sulfate and iodomethane, and inexpensive potassium carbonate is used as a base, so that the production cost is lowered, the method is environment-friendly, the yield is high, and the method is suitable for scaled industrial production.

The invention discloses a preparation method of 17 beta-androst-4-ene-3-one-17-carboxylic acid. The preparation method comprises that 4-androstenedione (called as 4AD for short) as a raw material andtriethyl orthoformate undergo a reaction in an organic solvent under acid catalysis, the reaction product is after-treated to form an etherate, the etherate is dissolved in an organic solvent and undergoes a reaction with trimethylsulfonium iodide under strong base catalysis, the product is after-treated to form an epoxide, the epoxide is dissolved in an organic solvent and then is subjected to rearrangement under acid catalysis to form an aldehyde, and aldehyde is dissolved in an organic solvent and undergoes a catalytic oxidation reaction with hydrogen peroxide acid to produce 17 beta-androst-4-ene-3-one-17-carboxylic acid. The 17 beta-androst-4-ene-3-one-17-carboxylic acid has a melting point of 244-246 DEG C, HPLC content of 99.0% or more and a reaction weight total yield of 70-72%. Compared with the traditional method, the preparation method utilizes cheap and easily available raw materials, has simple and environmental friendly processes and a high synthesis yield, produces highquality products, reduces a cost by 30-40% and is conducive to industrial production.

The invention provides a method for preparing boldenone through selective reduction. 1,4-androstenedione is used as a main raw material, the charging sequence is changed, the main raw materials are treated in advance, the charging mode of the main raw materials is changed, and the keto selective reduction reaction is carried out, thus, the boldenone is prepared. The method solves the problems that the existing boldenone preparation process has more steps, long period and high production cost. According to the preparation method, the production procedures are reduced, the production period is shortened, the operation is simple, the cost is low and the method is suitable for industrial production.

The invention relates to a synthesis method of a chemical medicine, and concretely relates to a synthesis method of a spironolactone intermediate canrenone. The method comprises the following steps: carrying out an ethynylation reaction on a compound I 4-androstenedione (4AD), hydrogenating, carrying out an oxidation cyclization reaction, and carrying out a bromization and debromination reaction to obtain the compound V canrenone, and the above reaction route is shown in the specification. A synthesis method of the structure of an important 21,17-carboxy lactone spiro ring adopted in the invention is different from previous process modes, and is concise and efficient. The method has the characteristics of high yield, good selectivity, low cost, mild reactions, suitableness for industrialization, stability and easy realization.

A preparation method for dehydroepiandrosterone, comprising: in a protective atmosphere, adding potassium tert-butoxide to tert-butanol, stirring evenly, adding 4-androstenedione to obtain a mixture,and adding the mixture dropwise to a sodium ascorbate-containing acetic acid solution for a reaction to obtain 5-androstenedione; dissolving the 5-androstenedione in an organic solvent, adding a ketone reductase, a glucose dehydrogenase, glucose and a redox coenzyme to obtain a mixture, controlling the pH of the mixture to be 6.0-6.3, stirring and reacting for 1-6 hours at 22-26 DEG C to obtain areaction solution, and performing separation and purification on the reaction solution to obtain dehydroepiandrosterone, the ketone reductase and the glucose dehydrogenase being coexpressed by a microbial strain and added in the form of a crude enzyme solution. The synthesis process of the preparation method has few steps, simple operations, high yields and low costs, and may be widely applied toindustrial scale production. Also provided is an enzyme for preparation.

The invention provides a method of preparing 4-androstenedione by fermentatively degrading phytosterol by virtue of a single water phase system. The method comprises the following step: 1, strain cultivation, namely inoculating a mycobacterium smegmatis stain into a seed medium and cultivating; 2, sterol emulsification, namely emulsifying the phytosterol as a substrate under the action of a surfactant; 3, fermentation cultivation, namely inoculating the mycobacterium smegmatis stain obtained in the first step in a fermentation medium, adding the phytosterol obtained in the second step and carrying out fermentation cultivation; 4, finished product extraction. According to the method of preparing the 4-androstenedione by fermentatively degrading the phytosterol by virtue of the single water phase system, an emulsifier is added, so that the yield of 4-androstenedione is increased, and the extraction technology of the 4-androstenedione is also simplified; the cost is low, the pollution is little, and the environmental protection pressure is weak.

The invention discloses a preparation method of androst-2-en-17-one. The method comprises the steps that 4-androstenedione is adopted as a raw material, three-step reactions of a protective reaction,a reduction reaction and a deprotection reaction are adopted for synthesizing epiandrosterone, in an organic solvent, a carrier solid phase acid catalyst soaked with acid is used for catalyzing, epiandrosterone dehydration is performed to eliminate 3-bit hydroxyls in molecules, and a target product is obtained. 4-androstenedione obtained by phytosterol extracted from a soybean oil deodorization distillate through the modern fermentation technology is adopted as a raw material; 4-androstenedione is subjected to the three-step reactions to synthesize a key intermediate epiandrosterone, and raw materials are abundant in source and low in price. The epiandrosterone is used for preparing a target product, compared with a traditional method, a synthetic route is cut into a one-step reaction fromtwo-step reactions, the method is economical and environmentally friendly, and production and operation are easier. By adopting the carrier solid phase acid catalyst soaked with acid for catalyzing,an oligomer makes indirect contact with the acid catalyst, the reactions are mild and stable, the dehydration elimination reactions are performed in the thermodynamics stable 2,3-bit directions, and the reaction selectivity is good.

The invention relates to a preparation method of methylprednisone. The method comprises the following steps: carrying out acid catalyzed reaction on 16(17)a-epoxy prednisone prepared from 4-androstenedione (4AD for short) and ethanediol in an organic solvent at 10-50 DEG C to obtain a ketal substance 20-ketal-16(17)a-epoxy prednisone; carrying out alkali catalyzed reaction on the ketal substance and trimethylchlorosilane in an organic solvent to obtain a silyl ether substance 21-methylsilyl-ether-20-ketal-16(17)a-epoxy prednisone; and carrying out Grignard reaction on the silyl ether substance and a 2M methyl grignard reagent in an organic solvent, hydrolyzing the Grignard substance in strong acid to obtain the methylprednisone. The detection indicates that the HPLC (high performance liquid chromatography) content is 99.0% or above, the melting point is 228-237 DEG C, and the synthetic weight total yield is 80-85%. When being used for producing methylprednisone, the method has the advantages of wide raw material sources, economical and environment-friendly technique, simple production operation, short synthesis route, high synthesis yield and lower production cost (than the traditional method by 30-40%). The method is convenient for industrial production.

The invention provides a method and process for extracting 4-androstenedione from phytosterol aqueous phase fermentation liquor. The method comprises the following steps: performing microbial fermentation on phytosterol serving as a raw material to generate 4-androstenedione; performing liquid-solid separation on the fermentation liquor generated at the end of fermentation through a centrifugal machine, and extracting a wet solid material; adding a acetone-purified water mixed solvent into the wet solid material, continuously stirring for 60-90 minutes under the condition that the temperature is raised to 40-60 DEG C, and performing solid-liquid separation under the temperature condition of higher than 40 DEG C; crystallizing the solution obtained through solid-liquid separation; centrifuging the crystallized material to obtain a coarse product of the 4-androstenedione, and refining the coarse product to prepare the finished 4-androstenedione product. According to the method, the impurities in the 4-androstenedione product can be reduced, and the extracting and refining process is simplified.

The invention discloses a technology for refining 4-androstenedione from a dehydroepiandrosterone mother solution. The technology comprises the steps that dehydroepiandrosterone is pretreated, reflux dehydration, addition of a weak oxidant, reflux dehydration and addition of aluminum isopropoxide for a reaction are carried out in sequence, an alkaline aqueous solution is added for a reaction, washing and distillation are carried out, and crude 4-androstenedione is obtained; then refining and purifying are carried out, and the 4-androstenedione product high in purity and yield is obtained.

The invention relates to a preparation method of 5alpha-androstane-3,17-dione. The method specifically comprises the following steps: 1, carrying out an etherification reaction on 4-androstenedione, triethyl orthoformate and anhydrous ethanol in the presence of an etherification catalyst, and performing post-treatment after the etherification reaction is completed in order to prepare a compoundwet 3-ethoxy-3,5-androstadien-17-one; 2, adding a the wet 3-ethoxy-3,5-androstadien-17-one into a methanol-dichloromethane mixed solvent, performing uniform stirring, adjusting the pH value of the obtained solution, carrying out a catalytic hydrogenation reaction under the action of a palladium-carbon catalyst, and filtering out the catalyst after the reaction is finished in order to obtain a 3-ethoxy-3-androstene-17-one solution; and 3, carrying out a hydrolysis reaction on the 3-ethoxy-3-androstene-17-tone solution and an acid, removing the solvent after the hydrolysis reaction is finished,and carrying out filtering, water washing and drying to obtain the 5alpha-androstane-3,17-dione. The method has the advantages of short process route, easily controlled production process, environmental friendliness, low production cost, and suitableness for industrial large-scale production.

The invention discloses a synthetic method for ethisterone. The synthetic method comprises the following steps that firstly, 4-androstenedione and triethyl orthoformate serve as reaction raw materials, an etherification reaction is conducted, triethylamine is added to adjust the pH value of reaction materials, a crystal is obtained through filtering after cooling, and etherate I is obtained after washing and drying; secondly, dehydration is conducted after methylbenzene, potassium hydroxide and isobutanol are evenly mixed, tetrahydrofuran is added into dehydrated mixed liquid, and acetylene gas is led in until the acetylene gas is not absorbed; thirdly, the dissolved etherate I is added into the mixed liquid, the acetylene gas is led in for a reaction, and sulfuric acid is added until the pH value reaches 1-2; fourthly, the material obtained after the pH value is adjusted is distilled and concentrated, then the distilled and concentrated material is washed to be neutral through water, and an ethisterone crude product is obtained after drying; fifthly, the ethisterone crude product is refined. The synthetic method for the ethisterone has the advantages that reaction conditions are moderate, operation is simple and convenient, reaction steps are few, reaction products are single, and the yield is high. The synthetic method is suitable for industrial production.

The invention relates to a preparation method for finasteride intermediate. According to the method, a product compound I, namely N-tert-butyl-3-oxo-4-olefinic-17 beta-finasteride formamide intermediate, is prepared by carrying out two steps of cyaniding and amidation on a compound II, namely androstenedione. A reaction scheme is shown in the specification. 4-androstenedione is used as a raw material, the resource is richer, and the cost is lower; the synthesis time is short, and the obtained finasteride intermediate is high in purity yield, and the HPLC is greater than or equal to 98%; and the yield is greater than or equal to 110%.

The invention provides a method of synthesizing testosterone through the 4-androstenedione one-step method. The method is characterized by comprising the following steps: Step 1, dissolving androstenedione in a mixed solvent system which is 4-14 times heavier than the androstenedione in weight, and cooling the mixture below minus 10 DEG C; Step 2, dissolving potassium borohydride in purified water which is 7-14 times heavier than potassium borohydride in weight; Step 3, adding the solution prepared in the Step 2 to the feed liquid which is obtained in the Step 1, 4-14 times heavier than the androstenedione and is at minus 5 to minus 10 DEG C; Step 4, taking a reaction at a condition of minus 5 to minus 10 DEG C until androstenedione is completely reacted, adding glacial acetic acid which is 15-40% of the weight of the potassium borohydride to demage excessive potassium borohydride, reducing the pressure, recovering the solvent, adding water, filtering and obtaining a crude product; Step 5, recrystallizing the crude product with ethanol to obtain the finished testosterone product.

The invention discloses a method for converting and purifying 4-androstenedione from mother solutions of allyl ester substances and ketal substances. According to the method, 4-androstenedione is prepared from an allyl ester mother solution and a ketal substance mother solution which are prepared during the preparation of dehydroepiandrosterone, so that the repeated use of waste is realized, and the method is environmentally friendly and economic; the reaction route is greatly shortened, so that the generation of intermediate side reaction products is prevented, and the product purify and yield are high; and furthermore, the consumption of the reaction raw materials is relatively low, so that the cost is saved, and the requirement of green production idea is met.

The invention provides a preparation method of a 1,6-didehydrogenation-17a-hydroxyl progesterone product. The preparation method includes the steps that 1,4-androstenedione (IDD) is adopted as a raw material, firstly, IDD molecules and acetone cyanohydrin react in a first organic solvent under the catalyzation of alkali, so that a hydroxyl-cyanogen product is obtained; then the hydroxyl-cyanogen product is prepared into 1,6-didehydrogenation-17a-hydroxyl progesterone under the existence of methyl magnesium halide, a second organic solvent and acid; then 1,6-didehydrogenation-17a-hydroxyl progesterone is subjected to heating reflux and decoloration in methylbenzene, acetone or lower alcohol of C4 or below and recrystallized, so that the1,6-didehydrogenation-17a-hydroxyl progesterone productis obtained. With the IDD being the raw material, compared with the traditional production method that dioscin is used as a raw material, the preparation method has the advantages of being wide in source of the raw material, making the technology economic and environmentally friendly and lowering production costs substantially. In the preparation method, expensive and toxic DDQ and a chloranil dehydrogenating agent do not need to be used; the solvent used in the technology can be recycled and applied mechanically, economy and environmental protection are realized, and industrialized production is quite easy.