Biocatalytic Enantioselective Synthesis of Chiral β-Hydroxy Nitriles Using Cyanohydrins as Cyano Sources

Abstract

The development of catalytic enantioselective cyanation methods for preparing valuable chiral nitriles is of great interest in the areas of pharmaceutical synthesis and organic chemistry. In this study, we presented an enzymatic enantioselective cyanation strategy for the synthesis of chiral β-hydroxy nitriles using cyanohydrins as cyano sources. By combining enzyme screening and protein engineering of halohydrin dehalogenases, biocatalytic enantioselective cyanation of various aryl, alkyl, and spiro epoxides was achieved to afford the corresponding chiral β-hydroxy nitriles in good yields (up to 47%) and excellent optical purities (up to >99% ee). Additionally, we also demonstrated that the biocatalytic cyanation method can be used for the enantiocomplementary and large-scale synthesis of chiral β-hydroxy nitriles.