Control of enantioselectivity in the enzymatic reduction of halogenated acetophenone analogs by substituent positions and sizes

Abstract

We utilized acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD), wild type and Trp288Ala mutant, to reduce halogenated acetophenone analogs to their corresponding (S)- and (R)-alcohols beneficial as pharmaceutical intermediates. Reduction by wild type resulted in excellent (S)-enantioselectivity for all of the substrates tested. Meanwhile, reduction by Trp288Ala resulted in high (R)-enantioselectivity for the reduction of 4′ substituted acetophenone and 2′-trifluoromethylacetophenone. In addition to that, we were able to control the enantioselectivity of Trp288Ala by the positions and sizes of the halogen substituents.