Catalytic Promiscuity of Fatty Acid Photodecarboxylase Enables Stereoselective Synthesis of Chiral α‐Tetralones
Weihua Xu, Kaihao Mou, Zhenyu Lu, Xiu‐Wen Kang, Yue Guo, Bei Ding, Zhirong Chen, Zhiguo Wang, Qi Wu
Abstract
Abstract In the field of biocatalysis, discovering novel reactivity from known enzymes has been a longstanding challenge. Fatty acid photo‐decarboxylase from Chlorella variabilis ( Cv FAP) has drawn considerable attention as a promising photoenzyme with potential green chemistry applications; however, its non‐natural reactivity has rarely been exploited to date. Herein we report a non‐natural reductive dehalogenation (deacetoxylation) reactivity of Cv FAP inspired by its natural oxidative decarboxylation process, enabling the stereoselective synthesis of a series of chiral α‐substituted tetralones with high yields (up to 99 %) and e.r. values (up to 99 : 1). Mechanistic studies demonstrated that the native photoenzyme catalyzed the reductive dehalogenation via a novel mechanism involving oxidized state (FAD ox )/semiquinone state (FAD sq ) redox pair and an electron transfer (ET)/proton transfer (PT) process of radical termination, distinct from the previous reports. To our knowledge, this study represents a new example of Cv FAP promiscuity, and thus expands the reactivity repertoire of Cv FAP and highlights the versatility of Cv FAP in asymmetric synthesis.