Biological preparation method of (3R, 5R)-6-cyano-3,5-dyhydroxytert-butylhexanoate

Abstract

The embodiment of the invention provides a biological preparation method of (3R, 5R)-6-cyano-3,5-dyhydroxytert-butylhexanoate and belongs to the field of biological pharmacy. The preparation method comprises the following steps: by taking (5R)-6-chloro-5-hydroxy-3-tert-butyloxohexanoate as a raw material in a triethanolamine hydrochloride buffer solution, maintaining the pH value to be 6-8 under the actions of a complex enzyme of recombinant ketoreductase and glucose dehydrogenase, dehalogenase, a cofactor and glucose by using a cyaniding reagent, and reacting to obtain the (3R, 5R)-6-cyano-3,5-dyhydroxytert-butylhexanoate at room temperature. According to the preparation method provided in the invention, the (5R)-6-chloro-5-hydroxy-3-tert-butyloxohexanoate is taken as the raw material, a reduction reaction and a cyano substitution reaction are finished to obtain the product through a one-pot method under the catalysis of the complex enzyme of recombinant ketoreductase and glucose dehydrogenase and the dehalogenase, and the method is simple in process and low in production cost.

Description

technical field

[0001] The invention belongs to the field of biopharmaceuticals, and in particular relates to a biological preparation method of atorvastatin intermediate (3R,5R)-6-cyano-3,5-dihydroxyhexanoic acid tert-butyl ester. Background technique

[0002] Statins reduce low-density lipoprotein cholesterol (LDL-C) levels by inhibiting HMG-CoA reductase in the cholesterol synthesis pathway, and have a good effect on hyperlipidemia mainly caused by elevated cholesterol. Widely used lipid-regulating drugs. Atorvastatin (Atorvastatin) has become a new third-generation, fully synthetic, highly purified, and highly selective HMG-CoA reductase inhibitor due to its advantages of rapid onset of action, strong lipid-lowering effect, and long action time. The most promising statin drugs in the market. And (3R,5R)-6-cyano-3,5-dihydroxyhexanoic acid tert-butyl ester is the most important intermediate of atorvastatin, therefore, the development of (3R,5R)-6-cyano-3 , The synthetic...

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