Sglycosidic

S‑glycosidic compounds, commonly referred to as thioglycosides, are carbohydrates in which the anomeric oxygen of a glycosidic bond is replaced by a sulfur atom. This substitution results in an S‑glycosidic linkage, which is more resistant to enzymatic hydrolysis than the typical O‑glycosidic bond found in most natural polysaccharides. Thioglycosides can be synthesized chemically by reacting a protected sugar hemiacetal with a thiol nucleophile under acidic or catalytic conditions, often employing Lewis acids such as BF₃·OEt₂ or promoters like N‑iodosuccinimide.

The structural features of S‑glycosidic bonds affect the conformation and stability of the resulting molecules. The larger atomic radius of sulfur compared with oxygen lengthens the bond and reduces the electronegativity, influencing the anomeric effect and the preferred stereochemistry at the anomeric centre. These factors can be exploited in the design of glycosidase inhibitors, as the sulfur atom mimics the transition state of glycosidic bond cleavage, leading to potent, often irreversible inhibition.

Thioglycosides are employed in a range of applications. In medicinal chemistry, they serve as building blocks for synthetic vaccines, antiviral agents, and as tools for probing carbohydrate‑protein interactions. In glycochemistry, S‑glycosidic linkages act as protective groups that can be selectively removed under mild conditions, facilitating iterative oligosaccharide synthesis. Additionally, natural thioglycosides have been isolated from certain plants and microbes, where they may function as defensive metabolites.

Research continues to explore the physicochemical properties of S‑glycosidic bonds, their biological roles, and their utility in constructing stable carbohydrate analogues for therapeutic and analytical purposes.