A universal O-glycosylation platform enabled by pyridinium catalysis using gas-releasing oxazolidinone-based carbamates donors

Abstract

Abstract Chemical glycosylation facilitates the scalable synthesis of structurally well-defined carbohydrates for functional studies and therapeutic development, with progress being driven by donors and strategies. Herein, we present an efficient and versatile O -glycosylation method utilizing newly designed, bench-stable and readily accessible oxazolidinone-based glycosyl carbamates as donors. This reaction is catalyzed by 2-pentafluorophenyl pyridinium salts under mild conditions and demonstrates elegant performance compared to conventional promoters. This robust protocol facilitates orthogonal, iterative and latent-active glycosylations for streamlined synthesis of oligosaccharides. Mechanistic studies, including NMR, deuteration and kinetic isotope effect experiments, establish that the pyridinium catalyst initiates glycosylation by first binding glycosyl acceptors. It then activates carbamate donors via CO₂ release to generate the oxocarbenium ion, which is identified as the rate-determining step of the glycosylation process.