Process for enantioselective enzymatic reduction of keto compounds
AssigneeDr. Reddy's Laboratories, Inc.
InventorsShahed HUSSAIN, Matthew BYCROFT
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Abstract
The present application relates to enantioselective enzymatic reduction of keto compounds to the corresponding chiral hydroxy compounds. Specifically the present application describes enantioselective enzymatic reduction of ethyl-4-chloroacetoacetate (compound of formula I) into (R)-ethyl-4-chloro-3-hydroxybutyrate (compound of formula II). The present application also covers use of (R)-ethyl-4-chloro-3-hydroxybutyrate prepared by the enantioselective enzymatic reduction process in the preparation of SGLT2 inhibitor empaglifiozin.
Claims10
A process for enantioselective enzymatic reduction of keto compound of formula I
- in which R represents a hydrogen atom or a C1-5 alkyl group, comprising,
- treating a mixture comprising:
- (a) an (R)-specific oxidoreductase obtained from Candida parapsilosis in the range of about 5 mg to about 50 mg per gram of compound of formula I,
- (b) a buffer having pH in the range of 6 to 7, and
- (c) 2-propanol,
- with the compound of formula I in the presence of a cofactor and zinc to form a chiral hydroxy compound of formula II
A process for isolation of CpADH enzyme, comprising:
- (d) lysing the cells expressing the enzyme CpADH by high pressure homogenization at a pH of 6 to 7 to obtain a crude extract,
- (e) adding zinc sulphate or zinc chloride to the crude extract,
- (f) optionally the material is clarified by the addition of polyethyleneimine, and
- (g) drying the solution using a lyophilizer to obtain the CpADH enzyme.
Dependencies are inferred from the claim text.