Asymmetric Reduction of N-[4-(2-Bromoacetyl)phenyl]methanesulfonamide by Employing Candida viswanathii MTCC 5158

Abstract

Enantioselective synthesis of chiral drugs by chemoenzymatic processes have attracted attention in which the crucial stereogenic step involves an enzymatic reaction by virtue of chemo-, regio- and enantio-selectivity and eco-friendly nature of biocatalysis, (S)-sotalol a b-blocker, belongs to class-III antiarrhythmic agents. To avoid the side effects of racemic sotalol, efforts have been put forward to synthesize a key intermediate for the synthesis of (S)-enantiomer of sotalol, which is more potent than the (R)-enantiomer. The aryl ketone, N-(4-acetylphenyl) methanesulfonamide was synthesized from the initial substrate 4-aminoacetophenone. Further, the bromination of aryl ketone was carried out to obtain N-[4-(2-bromo-acetyl)-phenyl]-methanesulfonamide. The chemical reduction as well as biological reduction of aryl ketone was carried out to obtain a racemate alcohol N-[4-(2-bromo-1-hydroxy-ethyl) (4-methanesulfonamide)]ethanol and chiral (S)-N-[4-(2-bromo-1-hydroxy-ethyl)(4- methanesulfonamide)]ethanol, respectively. (S)-N-[-4-(2-bromo-1-hydroxy-ethyl)(4- methanesulfonamide)]ethanol is a key intermediate for the synthesis of (S)-sotalol. The biological reduction was carried out by using whole cells and found that 96 % conversion was obtained at 12^th h of reaction after that the percentage conversion decreased.