Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for preparing 1,6-bi-dehydrogenized-17a-hydroxy progesterone

A technology of hydroxyprogesterone and double dehydrogenation, applied in the direction of steroids, organic chemistry, etc., can solve the problems of complicated production process operation, rising production costs, and increased production costs, and achieve simple and environmentally friendly processes, reduced production costs, and high quality Good results

Inactive Publication Date: 2019-03-29
HUNAN KEREY BIOTECH
View PDF15 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The 1,6-didehydro-17a-hydroxyprogesterone production process uses relatively expensive and toxic DDQ and chloranil dehydrogenation agents to dehydrogenate the 1-position and 6-position of the 17a-hydroxyprogesterone molecule respectively, The quality of the product obtained after each step of reaction treatment is poor, and all need to be treated with a large amount of alkaline water, resulting in more waste water, which is not easy to handle and easily pollutes the environment; the production process is complicated to operate, and the total yield of the two-step synthesis is less than 45%, and the production cost is high. More importantly, with the depletion of wild yam plant resources, and the artificial planting of yam plants, the production costs of saponin and dienes have doubled due to the increasing cost of labor and chemical fertilizers, resulting in 1,6- The production cost of didehydro-17a-hydroxyprogesterone has further increased, resulting in an increase in the production cost of CPA

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing 1,6-bi-dehydrogenized-17a-hydroxy progesterone
  • Method for preparing 1,6-bi-dehydrogenized-17a-hydroxy progesterone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] A: Preparation of Hydroxycyanide

[0040] In a 1000ml three-neck flask, add 100g of starting material IDD and 250ml of acetone cyanohydrin, control the temperature to 40-45°C, stir to completely dissolve IDD, then control the temperature at 20-25°C, and slowly add 2% carbonic acid dropwise Sodium alkali aqueous solution, about 2-2.5 hours to drop, then keep warm at 25-30°C for 2-3 hours, TLC to confirm the reaction end point, after the reaction, concentrate under reduced pressure to recover 90-95% of the solvent acetone cyanohydrin, and the remaining Thing is cooled to 20~25 ℃, then adds 500ml tap water water analysis, filters, and filtrate is sent to waste water treatment station for processing, and filter cake is crystallized with 500ml 40% alcohol aqueous solution, obtains hydroxycyanide 98.6g, HPLC content 98.2%, weight yield 98.6%.

[0041] B: Preparation of 1,6-didehydro-17a-hydroxyprogesterone

[0042] In a 1000ml three-neck flask, add 35g of magnesium powder a...

Embodiment 2

[0045] A: Preparation of Hydroxycyanide

[0046] In a 1000ml three-neck flask, add 100g of starting material IDD, 50ml of acetone cyanohydrin, and 500ml of methanol, control the temperature to 40-45°C, stir to completely dissolve IDD, then control the temperature at 20-25°C, slowly add 2 % sodium hydroxide alkaline aqueous solution, drop it in about 2-2.5 hours, then keep warm at 25-30°C for 2-3 hours, TLC confirms the reaction end point, after the reaction, concentrate under reduced pressure to recover 90-95% methanol and acetone The mixed solvent of cyanohydrin was applied mechanically, the residue was cooled to 20-25° C., and then 500 ml of tap water was added for water analysis, filtered, and the filtrate was sent to the waste water treatment station for treatment. The filter cake was crystallized with 500 ml of 40% alcohol aqueous solution to obtain 97.8 g of hydroxycyanide. HPLC content 98.5%, weight yield 97.8%.

[0047] B: Preparation of 1,6-didehydro-17a-hydroxyproge...

Embodiment 3

[0051] A: Preparation of Hydroxycyanide

[0052] In a 1000ml three-necked flask, add 100g of starting materials IDD, 50ml of acetone cyanohydrin, and 500ml of DME, control the temperature to 40-45°C, stir to completely dissolve IDD, then control the temperature at 20-25°C, and slowly add 2% Triethylamine alkali aqueous solution, drop it in about 2-2.5 hours, then keep warm at 25-30°C for 2-3 hours, TLC confirms the reaction end point, after the reaction, concentrate under reduced pressure to recover 90-95% of DME and acetone cyanide The mixed solvent of alcohol is used mechanically, the residue is cooled to 20-25°C, and then 500ml of tap water is added for water analysis, filtered, and the filtrate is sent to the waste water treatment station for treatment. The filter cake is crystallized with 500ml of 40% alcohol aqueous solution to obtain 96.2g of hydroxycyanide, HPLC Content 98.2%, weight yield 96.2%.

[0053] B: Preparation of 1,6-didehydro-17a-hydroxyprogesterone

[005...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a method for preparing 1,6-bi-dehydrogenized-17a-hydroxy progesterone. The method comprises the following steps: firstly, adopting a nutrient medium and one or more microbial strain for performing microbial fermentation on phytosterol, thereby acquiring 1,4-androstenedione, namely, IDD; taking IDD as a raw material and reacting with acetone cyanohydrins in a first organic solvent under the condition of base catalysis, thereby acquiring hydroxyl cyanide; preparing the 1,6-bi-dehydrogenized-17a-hydroxy progesterone by using the hydroxyl cyanide under the existence of methyl magnesium halide, second organic solvent and acid. Compared with the traditional production method which uses diosgenin as the raw material, the method using IDD as the raw material according to theinvention has the advantages of extensive source of raw material, economical and environment-friendly process, greatly reduced production cost, and the like; in the invention, high-cost and toxic DDQand chloranil dehydrogenating agent are no longer used; solvents used in the process are recyclable, economical, environment-friendly and beneficial to industrial production.

Description

technical field [0001] The invention belongs to the preparation technology of steroid hormone drug intermediates, and in particular relates to a method for preparing 1,6-didehydro-17a-hydroxyprogesterone. Background technique [0002] Cyproterone acetate, referred to as CPA, commonly known as cyproterone, the chemical name is 6-chloro-1.2a-methine-17a-hydroxy-pregna-1,4-diene-3,20-di Ketone-17-acetate is a kind of progestin drug, which is mainly used clinically for female contraception, female acne, and the treatment of hirsutism and alopecia caused by excessive male androgen secretion, and is also used for male benign The treatment of diseases such as prostatic hypertrophy and early prostate cancer has a huge market. The production method of CPA is to extract diosgenin from the yam plant, and obtain the key intermediate 17a-hydroxyl by 8-step reactions such as protection, oxidation, cracking, elimination, epoxidation, austenitic oxidation, bromination, and debromination. ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07J7/00
CPCC07J7/0045
Inventor 左前进吴来喜羊向新
Owner HUNAN KEREY BIOTECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com