Silver-Assisted Gold-Catalysed Oligosaccharide Synthesis

Abstract

Anomeric azido glycosides serve as crucial intermediates in N-glycoside chemistry, enabling the synthesis of glycosyl amides, glycoconjugates, N- glycosyl heterocycles, and N-glycosyl triazoles, among other bioactive compounds. Glycosyl azides are typically synthesized from per-O- acetylated sugars using trimethylsilyl azide in the presence of various Lewis acids, including SnCl₄, TiCl₄, BF₃·OEt₂, and TMSOTf. We demonstrate the anomeric azidation of per-O-acetylated and per-O-benzoylated sugars using catalytic amounts of oxophilic AuBr₃, achieving good to excellent yields and stereoselectivity. A comprehensive structural investigation of flagellar protein in Methanococcus voltae unveiled a trisaccharide composed of β- ManNAc3NAcA6Thr-4-β-GlcNAc3NAcA-3-β-GlcNAc-Asn. The chemical structure of this trisaccharide glycan was both fascinating and presented a substantial synthetic challenge. We synthesized the challenging GlcNAc3NacA unit and glycosylations were carried out by employing silver- assisted gold-catalyzed glycosylation. The 2,3-diamino-2,3-dideoxy-β-mannuronate derivatives are found in various natural species and play important biological roles. Notably, they are present in Methanococcus maripaludis and Pseudomonas aeruginosa serotype O5. Their biological significance, coupled with the challenge of achieving β- selectivity, motivated us toward their synthesis. To construct this unit, we strategically designed a synthetic route via the altrosazide intermediate. To obtain β-selectivity, we explored the effects of remote participation and steric assistance of the altrosazide unit, and the glycosylations were carried out using cyclohexyl alkynyl carbonate donor activated under gold-silver catalysis.