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

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.