Process for enzymatic synthesis of (R)-4-cyano-3-hydroxybutyrate from sodium alginate immobilized halogenohydrin dehalogenase

Abstract

The invention relates to a process for enzymatic synthesis of (R)-4-cyano-3-hydroxybutyrate from sodium alginate immobilized halogenohydrin dehalogenase. The process comprises the following steps: firstly, mixing sodium alginate with HHDH, cross-linking with glutaraldehyde, embedding by using calcium chloride, immobilizing for 1 hour, after the immobilization rate of HHDH is greater than 46%, enabling immobilized enzyme and a substrate (S)-4-chlorine-3-hydroxybutyrate (ATS-4) to react for 4 hours till the generation rate of ATS-5 is not less than 70%, recycling HHDH, and performing secondary catalytic reaction, wherein the generation rate of ATS-5 is not less than 35%. By adopting the method of sodium alginate immobilized halogenohydrin dehalogenase, the immobilization velocity of sodium alginate to halogenohydrin dehalogenase is rapid, the immobilization rate is high, and after the sodium alginate immobilized halogenohydrin dehalogenase is recycled after first enzymatic synthesis of (R)-4-cyano-3-hydroxybutyrate, relatively high catalytic efficiency can be stilled maintained, and the immobilization effect is good.

Description

technical field [0001] The invention relates to a preparation method of an atorvastatin intermediate, in particular to a process for catalyzing the synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester by immobilizing halohydrin dehalogenase with sodium alginate, which belongs to medicine chemical industry. Background technique [0002] Scientists have discovered that statins not only have a powerful lipid-lowering effect, but also have multiple effects. They can improve intravascular cardiomyocyte remodeling and inhibit cardiac electrophysiological remodeling, prevent cardiomyocyte apoptosis and regulate cardiac autonomic function, etc. . The emergence of statins is an important milestone in the history of cardiovascular disease treatment, and it has become an assistant blood lipid regulating drug that is currently clinically used for all kinds of hyperlipidemia, prevention and treatment of atherosclerosis and coronary heart disease, and is also a well-known drug in t...

AI Technical Summary

Problems solved by technology

[0007] The microbial conversion method is to use the biological system or its multi-enzyme or single-enzyme system to catalyze the target substrate to convert one substance into another substance. The principle is to use enzymes to catalyze a special reaction; Various microorganisms, these microorganisms are rich in active enzymes and have strong vitality. Therefore, for the preparation of chiral substances, microbial transformation methods are widely used; microbial transformation methods have mild reaction conditions, high selectivity, fast reaction speed, and low cost. , high product yield, but there are many influencing factors and difficult to control, such as some substrates are insoluble and need to be added after treatment, and the microorganism itself is a multi-enzyme system, and side reactions will occur during the conversion process

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