Process for the enantioselective enzymatic reduction of intermediates

摘要

A process for the enantioselective enzymatic reduction of a keto compound of general formula I;
wherein R may represent any protective group for amino functions (tert. butyloxycarbonyl group (BOC), benzyloxycarbonyl group, 9-fluorenylmethoxycarbonyl group) and X═—Cl, —CN, —OH, Br, F.

主权项

1. A process for the enantioselective enzymatic reduction of a keto compound of general formula I:wherein R is any protective group for amino functions and X═Cl, CN, OH, Br, or F, to the hydroxy compound of general formula II (R,S-compound): wherein R and X have the same meaning as in formula I, with the keto compound being reduced with an isolated oxidoreductase in the presence of a cofactor NADH or NADPH, wherein the oxidoreductase a) comprises an amino acid sequence according to SEQ ID No: 1, or b) is a polypeptide having greater than 75% amino acid sequence identity to SEQ ID No: 1 and enantiomeric selectivity of greater than 80% toward the hydroxyl compound of general formula II, or c) is encoded by the nucleic acid sequence SEQ ID NO:16, or d) is encoded by a nucleic acid sequence which hybridizes to a full length sequence of SEQ ID NO:16 when hybridization is carried out in a 0.7-1 M NaCl solution at 60° C. and washing is carried out with a 0.1 to 0.5-fold SSC solution at 65° C. and enantiomeric selectivity of at least 80% toward the hydroxyl compound of general formula II.