Imine Reductase-Catalyzed, Radical-Mediated Asymmetric Cyano Group Migration

作者：An Liu, Yang Yang · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c13193 · 被引用次数：10 · 研究领域：Radical Photochemical Reactions、Cyclopropane Reaction Mechanisms、Metalloenzymes and iron-sulfur proteins

Functional group migration (FGM) reactions represent a fundamental class of transformations in organic chemistry, enabling the repositioning of functional moieties in nonobvious ways. However, catalytic asymmetric radical-mediated FGMs remain rare due to the inherent challenges of achieving catalyst-controlled enantioselectivity over free radical intermediates. Herein, we repurpose imine reductases (IREDs), a class of biotechnologically important enzymes known for their substrate promiscuity, to enable the first examples of catalytic asymmetric cyano group migration via a radical mechanism. An orthogonal set of radical enzymes, including Pba IRED Cym and Smi IRED Cym, was engineered, allowing both 1,4- and 1,5-cyano group migration reactions to occur in an enantiodivergent fashion. The use of the nonionic surfactant TPGS-1000 was found to improve both the yield and enantioselectivity of these cyano migration reactions. This biocatalytic process exhibited a broad substrate scope and is readily scalable, affording a rare example of chiral nonamine product assembly with imine reductases. More broadly, stereoselective radical biocatalysis with engineered IREDs and other versatile enzymes provides a potentially general solution to challenging asymmetric FGM reactions.