Carbon–Carbon Bond Formation at the Reducing End of Unprotected Oligosaccharides

Glycoconjugates refer to carbohydrates covalently linked to an aglycon (lipid or protein etc.) through an O-glycosidic bond; they play pivotal roles in diverse biological processes. Although they show potential as molecular probes and drug seeds, the applications of these bioactive compounds are otherwise limited due to their metabolic instability, since O-glycosidic linkages are easily cleaved by glycosidases. Therefore, several attempts have been taken to replace the oxygen atom in the O-glycosidic bond by carbon, nitrogen, or sulfur atom for improving its metabolic stability. Especially, C-glycosides are extremely stable against both chemical and enzymatic hydrolysis, and thus, are promising candidates for the development of carbohydrate-based drugs. Direct C-glycosidation reaction of unprotected sugars, which is highly atom- and step-economical, has been widely investigated in the last decade. The C-glycosidation is still challenging, since unprotected aldoses exist mainly in a thermodynamically stable cyclic hemiacetal form. Improving efficiency of nucleophilic attack on an open aldehyde form of the aldoses, which is otherwise a weak reaction in situ, is the key to accelerate the C-glycosidation reaction.