Asymmetric Conjugate Hydrocyanation of α,β-Unsaturated Aldehydes Catalyzed by Engineered 2-Deoxy-D-ribose-5-phosphate Aldolase.

ABSTRACT: The enantioselective conjugate hydrocyanation of α,β-unsaturated aldehydes remains a long-standing challenge in synthetic chemistry. Here, we report the redesign of 2-deoxy-D-ribose-5-phosphate aldolase (DERA) into an efficient biocatalyst capable of promoting the asymmetric conjugate addition of hydrogen cyanide (generated in situ from trimethylsilyl cyanide) to aromatic enals via an iminium activation pathway. The evolved variant DERA-CN enables the efficient formation of various C4-nitriles with high conversions (up to 99%) and good enantioselectivity (up to 98% e.e.). Control experiments revealed a stepwise process involving enzyme-catalyzed conjugate hydrocyanation followed by spontaneous 1,2-addition of cyanide. Substrates with various electron-donating and electron-withdrawing group

SUBMITTER: Zhou H 

PROVIDER: S-EPMC12790325 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature