Method for preparing dehydroepiandrosterone through conversion of plant sterols by resting cells

Abstract

The invention relates to a method for producing a steroidal drug intermediate, in particular to a method for preparing dehydroepiandrosterone through conversion of plant sterols by resting cells. Themethod includes the steps of 3-position hydroxyl protective reaction, bioconversion of the resting cells, hydrolysis and purification. According to the method, the plant sterols are used as raw materials to produce dehydroepiandrosterone, the raw materials are easily available, the production cost is reduced, the yield is higher, the reaction route is shorter, and reaction steps and post-treatmentsteps required by most traditional preparation methods are eliminated; and a resting cell conversion method is adopted, the conversion system is single in nutrition and low in risk of infection and has an adjustable bacterial volume, and good conversion ability can be ensured.

Description

technical field [0001] The invention relates to a production method of a steroid drug intermediate, in particular to a method for preparing dehydroepiandrosterone by transforming phytosterols into resting cells. Background technique [0002] Dehydroepiandrosterone (DHEA for short), the chemical name is 3β-hydroxyandrost-5-en-17-one, and the molecular formula is C 19 h 28 o 2 , is a C 19 Adrenal steroids are mainly secreted by the adrenal cortex, and gonads such as testes and ovaries also secrete a small amount. The research scope of their physiological activities involves anti-cancer, anti-aging and immune regulation, anti-diabetes, and prevention and treatment of tumors. In addition, DHEA plays a very important role in the synthesis of steroid drugs. With DHEA as the initial compound, many drugs with important physiological activities and medical value can be obtained by modifying its core or side chain. [0003] At present, the preparation methods of DHEA mainly includ...

AI Technical Summary

Problems solved by technology

The chemical method mainly relies on multi-step chemical reactions to complete. The traditional preparation process uses androstenedione as the raw material, and uses chemical methods to selectively reduce the 3-position ketone group to β-hydroxyl. However, the products obtained by chemical synthesis methods often contain a certain amount of The 3-position α hydroxyl isomer and other impurities, the yield is low and the steps are cumbersome, and the use of various organic reagents is easy to cause pollution

Patent No. CN201210316197.0 discloses a method for preparing dehydroepiandrosterone by microbial fermentation, using phytosterols as raw materials, using a protective agent to protect the 3-position β-hydroxyl, and using mycobacterial fermentation to prepare dehydroepiandrosterone Ketone, this method has effectively improved the yield of dehydroepiandrosterone, but in its mycobacterial fermentation step, oily fermentation conversion is adopted, the product fermentation time is long, and it is easy to produce a variety of products, and it is difficult to process, separate and purify, and it is worth further research. Improve

Patent No. CN201410414313.1 discloses a method for producing dehydroepiandrosterone by microbial fermentation. The 3β-hydroxysteroid dehydrogenase encoding gene MSMEG_5228 in Mycobacterium smegmatis is knocked out, and the recombinant Mycobacterium smegmatis single Water-phase fermentation transforms phytosterols to produce dehydroepiandrosterone, which improves the conversion rate and solves the environmental impact of waste oil produced in microbial fermentation. However, knocking out genes and constructing recombinant strains involves the field of genetic engineering and requires a large investment. High requirements and cumbersome process