CN109369760B - Method for preparing dehydromethyltestosterone - Google Patents
Method for preparing dehydromethyltestosterone Download PDFInfo
- Publication number
- CN109369760B CN109369760B CN201811550158.0A CN201811550158A CN109369760B CN 109369760 B CN109369760 B CN 109369760B CN 201811550158 A CN201811550158 A CN 201811550158A CN 109369760 B CN109369760 B CN 109369760B
- Authority
- CN
- China
- Prior art keywords
- reaction
- hours
- dehydromethyltestosterone
- idd
- stirring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0033—Androstane derivatives substituted in position 17 alfa and 17 beta
- C07J1/0037—Androstane derivatives substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being a saturated hydrocarbon group
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The invention provides a method for preparing dehydromethyltestosterone, which comprises the steps of firstly adopting a nutrient medium and one or more microbial strains to prepare 1, 4-androstenedione (IDD) after microbial fermentation of phytosterol,then the IDD is taken as a raw material, alpha-CH is introduced into the 17 th position in the presence of methyl magnesium halide, organic solvent and acid3And beta-OH, and preparing the dehydromethyltestosterone. Compared with the traditional method using diosgenin as a raw material, the method for preparing dehydromethyltestosterone by using IDD as the raw material has the advantages of wide raw material source, economic and environment-friendly process and greatly reduced production cost. Compared with the traditional production method, the method has the advantages of short synthetic route, simple and environment-friendly process, high product yield and good quality, and the cost of the production raw materials is reduced by 40-45 percent based on the price of the current raw materials.
Description
Technical Field
The invention belongs to a preparation process technology of steroid hormone medicaments, and particularly relates to a method for preparing a protein assimilation hormone medicament dehydromethyltestosterone.
Background
The dehydromethyltestosterone is a protein anabolic hormone medicament, has androgen action, is mainly clinically used for treating burns, wounds and postoperative treatment, treating malnutrition of children and the like, is also used for treating the recovery period of aplastic anemia and chronic consumptive diseases, patients who use adrenal cortical hormone for a long time or in large quantities, and the like, and has a large market.
The traditional production method of dehydromethyltestosterone is characterized by that it uses dioscin extracted from dioscorea plant, and makes it undergo the processes of protection, oxidation, cracking and elimination to obtain key intermediate dehydropregnenolone acetate (diene for short) as raw material, and makes it undergo the processes of oximation, Beckmann rearrangement and acid hydrolysis, etc. 3 steps of reaction to obtain dehydroepiandrosterone acetate, and then makes it undergo the processes of Grignard reaction, alkaline hydrolysis, austenitic oxidation and DDQ 1-position dehydrogenation to obtain the dehydromethyltestosterone, and its synthetic route is shown in figure 1. The processes of diosgenin extraction, oxidative cracking, Beckmann rearrangement, acid and alkali hydrolysis, DDQ dehydrogenation reaction and the like generate more waste water, are not easy to treat and pollute the environment; the austenite oxidation process adopted in the production needs steam distillation, and has large water consumption and energy consumption. More importantly, with the increasingly depleted wild yam plant resources, the production cost of saponin and diene is doubled due to the increasing planting cost of manpower, chemical fertilizers and the like for artificially planting yam plants, so that the production cost and market price of dehydromethyltestosterone are greatly increased, and the production cost and market price of the dehydromethyltestosterone have a great influence on the global dehydromethyltestosterone medicine market.
According to the structural characteristics of the product, specifically, the preparation of dehydromethyltestosterone has three key points, the first point is to convert the 17 th ketone group in the raw material into alpha-CH3And beta-OH; the second point is the introduction of a double bond at the 4-position; the third point is the introduction of a double bond at position 1. The most traditional method for producing dehydromethyltestosterone uses dehydroepiandrosterone acetate with double bond at 5-position as raw material, and firstly introduces alpha-CH at 17-position3And beta-OH, introducing a double bond at the 4-position while introducing a ketone group at the 3-position, and finally introducing a double bond at the 1-position to obtain the dehydromethyltestosterone, namely the scheme shown in figure 1 of the invention. Another preparation scheme of dehydromethyltestosterone is disclosed in the applicant's prior invention CN201710754305, in particular using the compound in which alpha-CH has been introduced in position 173And beta-OH as raw material, forming double-bromine meiandrosaponol at 1-position and 4-position, and forming double bonds at 1-position and 4-position to obtain dehydromethyltestosterone.
There is still a need in the art for a more superior method for the preparation of dehydromethyltestosterone.
Disclosure of Invention
The scheme of the invention is to directly use IDD with double bonds formed at the 1-position and the 4-position as raw materials, remove the ketone group at the 17-position and introduce alpha-CH3And beta-OH to obtain the dehydromethyltestosterone in one step.
Therefore, the invention provides a method for preparing dehydromethyltestosterone, which comprises the steps of firstly adopting a nutrient medium and one or more microbial strains to prepare 1, 4-androstenedione (IDD) after phytosterol is subjected to microbial fermentation, then taking the IDD as a raw material, and introducing alpha-CH at the 17 th position in the presence of methyl magnesium halide, an organic solvent and an acid3And beta-OH, and preparing the dehydromethyltestosterone.
In a specific embodiment, the methyl magnesium halide is methyl magnesium chloride, methyl magnesium bromide, or methyl magnesium iodide.
In a specific embodiment, the organic solvent is one or more of toluene, benzene, chloroform, tetrahydrofuran and dioxane, preferably tetrahydrofuran.
In a specific embodiment, the acid is an organic or inorganic acid, and is preferably one of acetic acid, p-toluenesulfonic acid, hydrochloric acid and sulfuric acid, more preferably hydrochloric acid.
In a specific embodiment, the reaction temperature is 30-100 ℃, and the reaction process comprises the steps of adding methyl magnesium halide into an organic solvent and IDD to perform a Grignard addition reaction, adding acid to hydrolyze Grignard compounds obtained by the Grignard addition reaction, and then recovering the organic solvent under reduced pressure and adding water to perform elutriation to obtain the dehydromethyltestosterone.
In a specific embodiment, the nutrient medium comprises one or more of glucose, corn steep liquor, inorganic salts, yeast extract, beef extract and peptone.
In a specific embodiment, the microbial species is one or more of the group consisting of mycobacteria, fusarium and bacillus amyloliquefaciens.
In the invention, IDD is dissolved in an organic solvent and undergoes a Grignard addition reaction with a solution of a methyl magnesium halide reagent to synthesize dehydromethyl testosterone in one step;
further, the specific operation of the synthesis is as follows:
a: preparation of Grignard reagents
Adding magnesium powder and an organic solvent into a reactor, stirring, controlling the temperature to 25-55 ℃, slowly introducing methyl alkyl halide, reacting for 4-6 hours until the magnesium powder completely disappears, and obtaining a Grignard reagent for later use;
b: preparation of dehydromethyltestosterone
Dissolving an initial raw material IDD in an organic solvent, stirring, controlling the temperature to 30-100 ℃, slowly dripping the prepared Grignard reagent for about 1-1.5 hours, keeping the temperature at 30-100 ℃ for reaction for 2-3 hours, confirming a reaction end point by TLC (thin layer chromatography), after the reaction is finished, slowly dripping acid, hydrolyzing for 2-3 hours, after the hydrolysis is finished, dividing water, washing with water, concentrating an organic layer under reduced pressure to recover the organic solvent, performing water separation by tap water, and crystallizing by using an alcohol water solution to obtain a crude dehydromethyltestosterone product, wherein the HPLC content is more than 98.0%, and the weight yield is 90-95%.
C: refining of dehydromethyltestosterone
Dissolving a dehydromethyltestosterone crude product in an organic solvent, adding activated carbon, carrying out reflux decolorization for 1-1.5 hours, filtering while hot, washing the carbon with a solvent with the volume 1 time of the weight of the crude product, recycling a filter cake to a manufacturer, combining a filtrate and a washing solution, concentrating the solvent under reduced pressure until crystals are separated out, cooling to-5-0 ℃ for crystallization for 3-4 hours, filtering, washing and drying to obtain a dehydromethyltestosterone product with the melting point of 165-168 ℃, the HPLC content of 99.0-99.5 percent, recycling a mother solution, wherein the total yield of the step is 90-95 percent, and the total synthesis yield is 84-88 percent.
The organic solvent in the synthesis of the Grignard reagent can be one or more of dichloromethane, toluene, diethyl ether, THF and the like; the methyl alkyl halide used in the synthesis can be methyl chloride, methyl bromide or methyl iodide; the synthesis reaction temperature of the Grignard reagent is 20-50 ℃; the weight ratio of reactants is as follows: magnesium: alkyl halide ═ 1 g: 2.5-4.0 g; the ratio of reactants to solvent is: magnesium: organic solvent ═ 1 g: 2-12 ml.
The organic solvent for Grignard reaction in the synthesis of dehydromethyltestosterone can be one or more of toluene, benzene, chloroform, tetrahydrofuran, dioxane, etc.; the acid used for hydrolysis can be organic acid such as acetic acid, p-toluenesulfonic acid, etc., and can also be inorganic acid such as hydrochloric acid, sulfuric acid, etc.; the reaction temperature of the Grignard reaction and the hydrolysis reaction is 30-100 ℃; the weight ratio of reactants is as follows: IDD: grignard reagent solution ═ 1 g: 5-15 ml; the ratio of reactants to solvent is: IDD: reaction organic solvent ═ 1 g: 2-10 ml.
The organic solvent used for refining dehydromethyltestosterone can be one or more of toluene, acetone, lower alcohol with carbon number below 4 such as methanol, ethanol, isopropanol, tert-butanol, etc.; refining at the controlled temperature of 40-100 ℃; the weight ratio of the materials is as follows: crude product: activated carbon 1 g: 0.03-0.10 g; the ratio of the crude product to the solvent is as follows: organic solvent ═ 1 g: 3-10 ml.
In particular, the most preferred process of the present invention is illustrated below:
the organic solvent in the Grignard reagent synthesis is preferably THF, so that the organic solvent is safe, environment-friendly and convenient to recover; methyl alkyl halide used in the synthesis is preferably methyl chloride, so that the method is economic and environment-friendly; the synthesis reaction temperature of the Grignard reagent is preferably 20-30 ℃; the weight ratio of the reactants is preferably as follows: magnesium: methyl chloride ═ 1: 2.8 of; the ratio of reactants to solvent is preferably: magnesium: THF ═ 1 g: 6 ml.
The organic solvent of the Grignard reaction in the synthesis of the dehydromethyltestosterone is preferably THF, and the post-treatment is convenient. The acid used for hydrolysis is preferably hydrochloric acid, and is cheap and high in quality; the reaction temperature of the Grignard reaction and the hydrolysis reaction is preferably 50-55 ℃; the weight ratio of the reactants is preferably as follows: IDD: grignard reagent solution ═ 1 g: 8ml of the solution; the ratio of reactants to solvent is preferably: IDD: reaction organic solvent ═ 1 g: 5 ml.
The organic solvent used for refining the dehydromethyltestosterone is preferably alcohol, so that the refining effect is good, and the method is safe, environment-friendly and convenient to recover; the refining temperature is preferably alcohol reflux temperature; the weight ratio of the materials is preferably as follows: crude product: activated carbon 1 g: 0.05 g; the ratio of the crude product to the solvent is preferred, and the crude product: organic solvent ═ 1 g: 5 ml.
The beneficial effects of the invention include:
1. compared with the traditional method using diosgenin as a raw material, the method for preparing dehydromethyltestosterone by using IDD as the raw material has the advantages of wide raw material source, economic and environment-friendly process and greatly reduced production cost. Compared with the traditional production method, the method has the advantages of short synthetic route, simple and environment-friendly process, high product yield and good quality, and the cost of the production raw materials is reduced by 40-45% by calculating the price of the current raw materials; the solvent used in the process can be recycled, is economical and environment-friendly, and is very beneficial to industrial production.
2. The melting point of the dehydromethyltestosterone product obtained by the invention is 165-168 ℃, the HPLC content is 99.0-99.5%, and the total synthesis yield is 84-88%.
Drawings
FIG. 1 is a scheme of a synthesis scheme for the conventional production of dehydromethyltestosterone.
FIG. 2 is a synthesis scheme of dehydromethyltestosterone produced in the present invention.
Detailed Description
In order to explain the gist and spirit of the present invention in more detail, several embodiments are described below.
In the following examples, the processes described each comprise the use of a step comprising separation by crystallization of a deodorized distillate from the production of soybean oil, in particular from a deodorized distillate from the production of soybean oil, for example as described in the prior art CN200680047150.1, cn200710014171.x or CN 101074258B. The phytosterols were then converted to 1, 4-androstadienedione, IDD, by microbial fermentation using methods known in the art, e.g., as described in CN 1250709C. And then also the following steps.
Example 1
A. Preparation of Grignard reagents
Adding 35g of magnesium powder and 800ml of tetrahydrofuran into a 1000ml three-necked bottle, stirring, keeping the temperature at 30-35 ℃, introducing 98g of methyl chloride, and continuing to stir for reaction for 4-6 hours after the introduction is finished until the magnesium powder basically disappears to obtain a Grignard reagent for later use;
B. preparation of dehydromethyltestosterone
Adding 100g of IDD and 500ml of THF into a 1000ml three-necked flask, stirring and heating to 50-55 ℃, slowly dropping 800ml of Grignard reagent solution, completing dropping for 1-1.5 hours, continuing to keep the temperature and stirring for reaction for 2-3 hours, detecting the reaction end point by TLC, after the reaction is completed, slowly dropping 2N hydrochloric acid to PH2-3, continuing to hydrolyze at 50-55 ℃ for 2-3 hours after the dropping is completed, detecting the hydrolysis by TLC, after the reaction is completed, concentrating under reduced pressure to obtain about 90-95% of THF, and treating the recovered THF for reuse. And adding 600ml of tap water into the residual liquid, cooling the system to 5-10 ℃, stirring and crystallizing for 2-3 hours, filtering, washing a filter cake to be neutral by using the tap water, and drying at the temperature of below 70 ℃ to obtain 94.6g of a crude dehydromethyltestosterone product with the HPLC content of 98.2% and the weight yield of 94.6%.
C. Refining of dehydromethyltestosterone
And (2) adding 100g of the crude dehydromethyltestosterone prepared in the step (B) and 500ml of alcohol into a 1000ml three-necked bottle, stirring at 30-35 ℃ to completely dissolve the crude dehydromethyltestosterone and 500ml of alcohol, adding 5g of activated carbon, heating and refluxing the mixture for 1.5-2 hours, cooling to 55-60 ℃, filtering while hot, soaking and washing a filter cake by using about 100ml of alcohol, recycling the filter cake, combining the filtrate and a washing solution, concentrating at normal pressure to recycle 88-90% alcohol, cooling the system to-5-0 ℃, stirring and crystallizing for 3-4 hours, filtering, recycling a solvent from the filtrate and a mother liquor material, washing the filter cake by using a small amount of 50% ethanol water solution, and drying at the temperature of below 70 ℃ to obtain 92.5g of the dehydromethyltestosterone product, wherein the melting point is 165-168 ℃, the HPLC content is 99.5%, and the weight yield is 92.5%.
Example 2
A. Preparation of Grignard reagents
Adding 35g of magnesium powder and 800ml of tetrahydrofuran into a 1000ml three-necked bottle, stirring, keeping the temperature at 40-45 ℃, introducing 120g of methyl bromide, and continuing stirring for reaction for 2-3 hours after the introduction is finished until the magnesium powder basically disappears to obtain a Grignard reagent for later use;
B. preparation of dehydromethyltestosterone
Adding 100g of IDD and 500ml of toluene into a 1000ml three-mouth bottle, stirring and heating to 50-55 ℃, slowly dropping 800ml of Grignard reagent solution prepared above, completing dropping for 1-1.5 hours, continuing to keep the temperature and stirring for reaction for 2-3 hours, detecting the reaction end point by TLC, after the reaction is completed, slowly dropping 2N hydrochloric acid to PH2-3, continuing to hydrolyze at 50-55 ℃ for 2-3 hours after the dropping is completed, detecting the hydrolysis by TLC, after the reaction is completed, concentrating under reduced pressure to obtain about 90-95% of mixture of THF and toluene, and treating the recovered mixture of THF and toluene for reuse. And adding 600ml of tap water into the residual liquid, cooling the system to 5-10 ℃, stirring and crystallizing for 2-3 hours, filtering, washing a filter cake to be neutral by using the tap water, and drying at the temperature of below 70 ℃ to obtain 93.8g of a crude dehydromethyltestosterone product, wherein the HPLC content is 98.5%, and the weight yield is 93.8%.
C. Refining of dehydromethyltestosterone
And (2) adding 100g of the crude dehydromethyltestosterone prepared in the step (B) and 500ml of isopropanol into a 1000ml three-necked bottle, stirring at 30-35 ℃ to completely dissolve the crude dehydromethyltestosterone and the isopropanol, adding 5g of activated carbon, heating and refluxing the crude dehydromethyltestosterone and the 500ml of isopropanol for 1.5-2 hours, cooling to 55-60 ℃, filtering while hot, soaking and washing a filter cake by using about 100ml of isopropanol, recycling the filter cake, combining a filtrate and a washing solution, concentrating the filtrate at normal pressure to recycle about 88-90% of isopropanol, cooling the system to-5-0 ℃, stirring and crystallizing for 3-4 hours, filtering, recycling a solvent from the filtrate and a mother liquid material, washing the filter cake by using a small amount of 50% of isopropanol aqueous solution, drying at the temperature of below 70 ℃ to obtain 93.8g of the dehydromethyltestosterone product, wherein the melting point is 165.5-167.5 ℃, the HPLC content is 99.3%, and the weight yield is 94.6%.
Example 3
A. Preparation of Grignard reagents
Adding 35g of magnesium powder and 800ml of diethyl ether into a 1000ml three-necked bottle, stirring, keeping the temperature at 30-35 ℃, dropwise adding 150g of methyl iodide, and continuing stirring for reaction for 4-6 hours after the methyl iodide is completely introduced until the magnesium powder basically disappears to obtain a Grignard reagent for later use;
B. preparation of dehydromethyltestosterone
Adding 100g of IDD and 500ml of benzene into a 1000ml three-mouth bottle, stirring and heating to 50-55 ℃, slowly dropping 800ml of Grignard reagent solution prepared above, completing dropping for 1-1.5 hours, continuing to keep the temperature and stirring for reaction for 2-3 hours, detecting the reaction end point by TLC, after the reaction is completed, slowly dropping 2N hydrochloric acid to PH2-3, continuing to hydrolyze at 50-55 ℃ for 2-3 hours after the dropping is completed, detecting the hydrolysis by TLC, after the reaction is completed, concentrating under reduced pressure to obtain a mixture of 90-95% of diethyl ether and benzene, and treating the recovered mixture of diethyl ether and benzene for reuse. And adding 600ml of tap water into the residual liquid, cooling the system to 5-10 ℃, stirring and crystallizing for 2-3 hours, filtering, washing a filter cake to be neutral by using the tap water, and drying at the temperature of below 70 ℃ to obtain 91.2g of a crude dehydromethyltestosterone product, wherein the HPLC content is 98.7%, and the weight yield is 91.2%.
C. Refining of dehydromethyltestosterone
And (2) adding 100g of the crude dehydromethyltestosterone prepared in the step (B) and 500ml of acetone into a 1000ml three-necked bottle, stirring at 30-35 ℃ to completely dissolve the acetone, adding 5g of activated carbon, heating and refluxing the acetone for 1.5-2 hours, cooling to 55-60 ℃, filtering while hot, soaking and washing a filter cake by using about 100ml of acetone, recycling the filter cake by a manufacturer, combining the filtrate and a washing solution, concentrating at normal pressure to recycle 88-90% of acetone, cooling the system to-5-0 ℃, stirring and crystallizing for 3-4 hours, filtering, recycling the solvent from the filtrate and a mother liquid material, washing the filter cake by using a small amount of 50% acetone aqueous solution, and drying at the temperature of below 70 ℃ to obtain 90.8g of the dehydromethyltestosterone product, wherein the melting point is 165-168 ℃, the HPLC content is 99.7%, and the weight yield is 90.8%.
The method provided by the invention has the advantages of short synthetic route, simple and convenient process operation, and economic and environment-friendly production. The defects of expensive synthesis raw materials, long synthesis route, complex process operation, difficult environmental protection treatment, high production cost and the like in the traditional production process are overcome.
The foregoing is a more detailed description of the invention in connection with specific preferred embodiments and it is not intended that the invention be limited to these specific details. For those skilled in the art to which the invention pertains, several simple deductions and substitutions can be made without departing from the spirit of the invention, and all shall be considered as belonging to the protection scope of the invention.
Claims (4)
1. A method for preparing dehydromethyltestosterone is characterized in that firstly, a nutrient medium and one or more microbial strains are adopted to prepare 1, 4-androstadienedione (IDD) after microbial fermentation of phytosterol, and then the IDD is used as a raw material, and alpha-CH is introduced into 17 th position in the presence of methyl magnesium halide, an organic solvent and acid3And beta-OH, preparing the dehydromethyltestosterone;
wherein, the preparation steps of Grignard reagent methyl magnesium halide and IDD for preparing dehydromethyl testosterone are as follows:
adding 35g of magnesium powder and 800ml of tetrahydrofuran, stirring, keeping the temperature at 30-35 ℃, introducing 98g of chloromethane, and continuing stirring for reaction for 4-6 hours after the introduction is finished until the magnesium powder basically disappears to obtain a Grignard reagent methyl magnesium chloride for later use; adding 100g of IDD and 500ml of THF, stirring and heating to 50-55 ℃, slowly dropping 800ml of Grignard reagent methyl magnesium chloride solution, completing dropping within 1-1.5 hours, continuing to keep the temperature and stir for reaction for 2-3 hours, detecting the reaction end point by TLC, after the reaction is completed, slowly dropping 2N hydrochloric acid to pH2-3, and continuing to perform hydrolysis reaction for 2-3 hours at 50-55 ℃;
or adding 35g of magnesium powder and 800ml of tetrahydrofuran, stirring, keeping the temperature at 40-45 ℃, introducing 120g of methyl bromide, and continuing stirring for reaction for 2-3 hours after introduction till the magnesium powder basically disappears to obtain a Grignard reagent methyl magnesium bromide for later use; adding 100g of IDD and 500ml of toluene, stirring and heating to 50-55 ℃, slowly dropping 800ml of Grignard reagent methyl magnesium bromide solution, finishing dropping for 1-1.5 hours, continuing to keep the temperature and stir for reaction for 2-3 hours, detecting the reaction end point by TLC, after finishing the reaction, slowly dropping 2N hydrochloric acid to pH2-3, and continuing to perform hydrolysis reaction for 2-3 hours at 50-55 ℃;
or adding 35g of magnesium powder and 800ml of diethyl ether, stirring, keeping the temperature at 30-35 ℃, dropwise adding 150g of methyl iodide, and after the methyl iodide is completely introduced, continuously stirring for reacting for 4-6 hours until the magnesium powder basically disappears to obtain a Grignard reagent methyl magnesium iodide for later use; adding 100g of IDD and 500ml of benzene, stirring and heating to 50-55 ℃, slowly dropping 800ml of Grignard reagent methyl magnesium iodide solution, completing dropping for about 1-1.5 hours, continuing to keep the temperature and stir for reaction for 2-3 hours, detecting the reaction end point by TLC, after the reaction is completed, slowly dropping 2N hydrochloric acid to pH2-3, and continuing to perform hydrolysis reaction for 2-3 hours at 50-55 ℃.
2. The method as claimed in claim 1, wherein the reaction process comprises adding methyl magnesium halide to organic solvent and IDD to perform Grignard addition reaction, adding acid to hydrolyze Grignard product obtained by Grignard addition reaction, recovering organic solvent under reduced pressure, adding water to perform elutriation to obtain the dehydromethyltestosterone.
3. The method of claim 1, wherein the nutrient medium comprises one or more of glucose, corn steep liquor, inorganic salts, yeast extract, beef extract, and peptone.
4. The method of claim 1, wherein the microbial species is one or more species selected from the group consisting of mycobacterium, fusarium and bacillus amyloliquefaciens.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811550158.0A CN109369760B (en) | 2018-12-18 | 2018-12-18 | Method for preparing dehydromethyltestosterone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811550158.0A CN109369760B (en) | 2018-12-18 | 2018-12-18 | Method for preparing dehydromethyltestosterone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109369760A CN109369760A (en) | 2019-02-22 |
| CN109369760B true CN109369760B (en) | 2021-01-01 |
Family
ID=65374304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811550158.0A Active CN109369760B (en) | 2018-12-18 | 2018-12-18 | Method for preparing dehydromethyltestosterone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109369760B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109456381A (en) * | 2018-12-18 | 2019-03-12 | 湖南科瑞生物制药股份有限公司 | A kind of preparation method of Delmadinone |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4488995A (en) * | 1984-02-06 | 1984-12-18 | E. R. Squibb & Sons, Inc. | Androstene-17β-alkylthiomethyl ethers |
| KR100432054B1 (en) * | 2001-05-11 | 2004-05-17 | (주)유진사이언스 | Microorganism having ability to convert sterol into Androst-4-ene-3,17-dione/Androsta-1,4-diene-3,17-dione and preparation method thereof |
| DK2486924T3 (en) * | 2006-04-22 | 2019-03-04 | Neurmedix Inc | Medicines and uses |
| CN107312051A (en) * | 2017-07-24 | 2017-11-03 | 湖南科瑞生物制药股份有限公司 | The preparation method of Mestanlone |
-
2018
- 2018-12-18 CN CN201811550158.0A patent/CN109369760B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN109369760A (en) | 2019-02-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107629101B (en) | Preparation method of 17 β -androst-4-ene-3-one-17-carboxylic acid | |
| NO129337B (en) | ||
| CN106397520A (en) | Preparation method of methyltestosterone | |
| CN105153258A (en) | Preparation method for 3-beta-hydroxyandrost-17-one | |
| CN104327146A (en) | Novel method of synthesizing 17 alpha-hydroxyl progesterone | |
| CN107629102B (en) | Preparation method of nomegestrol acetate | |
| CN109369760B (en) | Method for preparing dehydromethyltestosterone | |
| CN104119415B (en) | Method for preparing 17alpha-hydroxyprogesteron | |
| CN104561217B (en) | The synthetic method of 6a methylprednisolones | |
| CN101712712A (en) | Method for preparing 16-dehydropregnenolone acetate by multistage filtration and recrystallization | |
| CN105801651B (en) | A kind of synthetic method of 17 α hydroxyl progesterones | |
| CN107501373B (en) | A kind of preparation method of danabol | |
| CN109456378B (en) | Method for preparing dehydromethyltestosterone product | |
| CN109456379B (en) | Preparation method of dehydromethyltestosterone product | |
| CN109369761B (en) | Preparation method of dehydromethyltestosterone | |
| Zafar et al. | New metabolites from fungal biotransformation of an oral contraceptive agent: Methyloestrenolone | |
| CN106008660B (en) | The preparation method of deflazacort | |
| CN109422683A (en) | A method of synthesis 6- aldehyde radical phenanthridines class compound and its derivative | |
| DE60308388T2 (en) | 5-androsten-3beta-ol steroids and process for their preparation | |
| CN114276406B (en) | Preparation method of intermediate of deoxomilpine | |
| CN109627275A (en) | A kind of bis- dehydrogenation -17a- hydroxyl progesterone product preparation methods of 1,6- | |
| CN107312052A (en) | A kind of preparation method of Methyllprednisolone | |
| US3466279A (en) | Conessine derivatives | |
| CN107021991A (en) | A kind of preparation method of 16 β methyl steroids | |
| CN109456382A (en) | A method of preparing delmadinone acetate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |