Nitrene-mediated glycosylation with thioglycoside donors under metal catalysis

• DOI: 10.1126/sciadv.adu7747
• Publication Date: 2025-02-21T19:00:26Z
• Authors: Ziqian Bai; Zenghui Wei; Shiyang Zhu; Gang He; Hao Wang; Gong Chen
• Keywords: Nitrene

Glycosylation chemistry plays a pivotal role in glycoscience. Recent substantial developments have poised the field to address emerging challenges related sustainability, cost efficiency, and robust applicability complex substrate settings. The transition from stoichiometric activation metal-catalyzed methods promises enhanced chemoselectivity greater precision controlling glycosidic bond breakage formation, key overcoming existing obstacles. Here, we report nitrene-mediated glycosylation strategy using regular aryl sulfide glycosyl donors easily accessible 3-methyl dioxazolone as an activator under catalysis of iron or ruthenium. iron-catalyzed system demonstrates exceptional catalytic reactivity, requiring little 0.1 mole % catalyst at room temperature, works well for peptide substrates. ruthenium-catalyzed can accommodate acid-sensitive functional groups challenging low-reactivity acceptors. Mechanistic investigations unveiled unusual multistep pathways involving sulfur imidation via nitrene transfer sulfur-to-oxygen rearrangement N-acyl sulfilimines donors.