Enantioselective synthesis of (S)-α-cyano-3-phenoxybenzyl alcohol by lipase-catalyzed alcoholysis of racemic ester in organic medium

Enantioselective synthesis of (S)-α-cyano-3-phenoxybenzyl alcohol [(S)-CPBA] was successfully achieved by lipase-catalyzed alcoholysis of (R,S)-CPBA acetate [(R,S)-CPBAc] in organic medium after systematic optimization of catalysts, water activity, organic solvents and acyl acceptors. A commercially available Pseudomonas fluorescens lipase, Lipase AK (Amano), showed excellent enantioselectivity (eep > 99%, E = 568) and high alcoholysis activity (1.88 μmol min−1 mg enzyme−1) towards the (S)-ester. The lipase exhibited higher activities in organic solvents with higher hydrophobicity and lower water activity controlled by anhydrous sodium sulfate. The initial rate of alcoholysis was nearly the same for alcohols of short chains (C2-C5) and the optimal concentration for n-butanol was 200-500 mM. A celite-adsorbed preparation of Lipase AK was used repeatedly for eight times, without significant loss of enzyme activity.