Regioselective one-pot protection, protection–glycosylation and protection–glycosylation–glycosylation of carbohydrates: a case study with d-glucose

Abstract

Well-defined oligosaccharides are important requirements in evaluating structure–activity relationships to decipher the roles of carbohydrates in various physiological processes. These oligosaccharides are accessed mainly through chemical synthesis, which nonetheless remains a huge undertaking despite the many advances in recent years. A combinatorial and regioselective one-pot protection strategy was previously disclosed by us to reduce the effort and wastes associated with carbohydrate synthesis. With the tetra-trimethylsilylated 4-methylphenyl thioglucoside as the starting material, we herein show the one-pot preparations of diols, triols and fully protected derivatives of thioglucosides, and, more importantly, we generated building blocks in situ that effectively acted as glycosyl donors and glycosyl acceptors for further coupling with other monosaccharide building blocks. Our one-pot protection–glycosylation and protection–glycosylation–glycosylation approaches made use of the perceived reactivity differences between thioglycoside donors to conveniently supply disaccharide and trisaccharide skeletons as well as the backbone of a recently discovered compatible solute from two thermophilic bacteria of the Petrotoga species. The demonstrated protocol is another step in reducing the enormous work in carbohydrate synthesis and efficiently delivering sugar constructs for application in other areas of glycobiology.