Synthesis of C- and S-Glycosides

Substitution with a carbon or a sulfur atom of the oxygen that in saccharides links one sugar unit to another sugar or to an aglycon generates compounds defined as C-glycosides and S-glycosides, respectively. The interest in these classes of compounds lies in the metabolic stability of the glycosidic linkage, as useful characteristic for potential drugs (inhibitors, agonists, antagonists) of glycosidic nature. After a brief introduction on the biological relevance of C-glycosides and S-glycosides, the chapter describes the different approaches for the synthesis of both classes of compounds, defining the general strategies and the recent applications. C-glycosides have been synthesized not only taking advantage of the electrophilic character of the anomeric center of the sugar, but also converting it into an electrophile or a radical. Not only carbon nucleophiles, such as organometallic reagents, carbanions, silyl enolethers, or allylsilanes, but also electrophilic carbons such as aldehydes, or carbon radical scavengers such as acrylates, can be used. The synthesis of S-glycosides is much simpler and well defined, due to the strong nucleophilic character of thiols that well combines with the electrophilic character of the anomeric center.