Process for the enantioselective enzymatic reduction of hydroxy keto compounds

摘要

In a process for the enantioselective enzymatic reduction of a hydroxy ketone of general formula I;
wherein R1=C1-C6 alkyl and R2=—Cl, —CN, —OH, —H or C1-C6 alkyl, into a chiral diol of general formula II
;
wherein R1 and R2 have the same meaning as in formula I, the hydroxy ketone is reduced with an oxidoreductase in the presence of NADH or NADPH as a cofactor, wherein

a) the hydroxy ketone is provided in the reaction at a concentration of ≧50 g/l,

b) the oxidized cofactor NAD or NADP having formed is regenerated continuously by oxidation of a secondary alcohol of general formula RXRYCHOH, wherein RX, RY independently represent hydrogen, branched or unbranched C1-C8-alkyl and Ctotal≧3, and

c) the reduction of the hydroxy ketone and the oxidation of the secondary alcohol are catalyzed by the same oxidoreductase.

主权项

1. A process for the enantioselective enzymatic reduction of a hydroxy ketone of general formula I wherein R1=C1-C6 alkyl and R2=—Cl, —CN, —OH, —H or C1-C6 alkyl, to a chiral diol of general formula II wherein R1 and R2 have the same meaning as in formula I, wherein the hydroxy ketone is reduced with an oxidoreductase in the presence of a cofactor, wherein the oxidoreductase a) comprises the amino acid sequence of SEQ ID NO:1, b) is encoded by the nucleic acid sequence SEQ ID NO:2 or SEQ ID NO:3, or c) is encoded by a nucleic acid sequence which hybridizes to SEQ ID NO:2 or SEQ ID NO:3 under stringent conditions comprising washing with 0.1-2.0×SSC solution at 65° C.