Asymmetric Synthesis of Both Antipodes of β-Hydroxy Nitriles and β-Hydroxy Carboxylic Acids via Enzymatic Reduction or Sequential Reduction/Hydrolysis

Abstract

Use of isolated carbonyl reductases in the reduction of aromatic beta-ketonitriles have completely eliminated the competing alpha-ethylation, which is often observed with whole cell biocatalysts. By choosing suitable recombinant carbonyl reductase, the reduction of beta-ketonitriles afforded (R)- or (S)-beta-hydroxy nitriles with excellent optical purity and yield. Subsequently, nitrilase-catalyzed hydrolysis of the obtained optically pure beta-hydroxy nitriles led to the corresponding beta-hydroxy carboxylic acids in high yields. More importantly, the sequential enzymatic reduction and hydrolysis could be carried out in "two-step-one-pot" fashion without the isolation of intermediates beta-hydroxy nitriles, lowering the cost and minimizing the environmental impact. This allows ready access to both antipodes of chiral beta-hydroxy nitriles and beta-hydroxy carboxylic acids of pharmaceutical importance with excellent optical purity.