Synthesis of CH₂-Linked Isomaltose via α-Selective Photoredox Vinyl C-Glycosylation

Abstract

C-Glycoside analogs of bioactive glycans and glycoconjugates are resistant to glycosidic hydrolysis and thus represent valuable scaffolds for drug discovery and chemical biology. We previously found that CH₂-linked isomaltose (CH₂-IM) exhibits potent amylase-inducing activity in Aspergillus nidulans compared to its native and linkage-edited counterparts. Here, we report a streamlined synthesis of CH₂-IM via photoredox-catalyzed vinyl-C-glycosylation using N,N-dialkylbenzylamine derivatives as efficient halogen-atom transfer reagents. This approach enables concise access to CH₂-IM and also facilitates the synthesis of 6′-modified analogs, providing a versatile platform for probing structure–activity relationships of IM derivatives. Notably, functionalization at the 6′- and anomeric positions completely abolishes the amylase induction activity.