Method for preparing dehydroepiandrosterone through chemical-enzyme method

Abstract

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.

Description

Technical field [0001] The invention relates to the field of pharmacy, in particular to a method for preparing dehydroepiandrosterone by a chemical-enzymatic method. Background technique [0002] Dehydroepiandrosterone (DHEA) has the structure shown in Formula 1. It is a steroid compound secreted by the adrenal cortex of the human body. It has the effects of delaying aging and resisting diseases. It is also a precursor for the synthesis of other steroid drugs. [0003] [0004] Among the methods for preparing dehydroepiandrosterone that have been published, most of them are fermentation and chemical methods. The fermentation method of adding the precursor to the microbial fermentation broth for biotransformation is reported in the patent CN 201210316197, etc., which takes a long time, the product content is less than 1 g / L, and there are problems such as separation and extraction. Starting with other steroids, such as reported in patents CN102212099, 102603841, 102603839, etc., pr...

AI Technical Summary

Problems solved by technology

[0006] In the reported 4-AD to 5-AD reaction, the purity of 5-AD is the main problem affecting the next step of the reaction, because its impurities are difficult to remove, and there is generally a high amount of potassium tert-butoxide, and the product 5-AD has a high yield. The problem of low yield, such as the amount of potassium tert-butoxide in the patent WO2014188353 is 5 times the equivalent of the substrate, and the product yield is only 83%. Considering that the substrate accounts for about 80% of the cost of the product dehydroepiandrosterone, there is greater difficulty in application

It is also worth noting that the second-step biosynthesis of this patent uses NAD and NADP as coenzymes at the same time, the amount of organic solvent is high, and the yield is 70%, which also has practical problems

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