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

作者：Xue-E Guan, Run‐Ping Miao, Xia Hua, Xiao Jin, Guozhong Deng, Bao‐Dong Cui, Wen‐Yong Han, Nan‐Wei Wan, Yong‐Zheng Chen · 发表于：ACS Catalysis · 年份：2023 · DOI：10.1021/acscatal.3c03173 · 被引用次数：18 · 研究领域：Enzyme Catalysis and Immobilization、Asymmetric Hydrogenation and Catalysis、Pharmacogenetics and Drug Metabolism

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.