Organo-Cation Catalyzed Enantioselective α-Hydroxylation of Pyridinone-Fused Lactones: Asymmetric Synthesis of SN-38 and Irinotecan

Abstract

A catalytic asymmetric α-hydroxylation of pyridinone-fused lactones, containing the core structure of camptothecin, is described. Development of a novel spiropyrrolidine amide (SPA) derived triazolium bromide organo-cation catalyst is crucial for a highly enantioselective oxidation, which also accommodates a wide array of lactones with various substituents. The resulting tricyclic tertiary alcohol with an oxa-quaternary carbon center can be further applied in the synthesis of SN-38 and irinotecan, two anti-cancer drugs derived from camptothecin.