thioglycoside

A thioglycoside is a type of glycoside in which the glycosidic linkage at the anomeric carbon (C1) is formed with sulfur instead of oxygen. In a thioglycoside, the anomeric carbon is connected to a sulfur-containing substituent, typically an aryl or alkyl thio group such as S-phenyl, S-phenyl, S-alkyl, or thioaryl derivatives. These compounds are widely used as glycosyl donors in carbohydrate chemistry and can serve as protective groups for the anomeric position during multistep syntheses.

Thioglycosides are generally more chemically robust than their O-glycoside counterparts, especially toward acidic hydrolysis, which makes them convenient for selective deprotection steps in complex syntheses. Their reactivity is governed by the ability to generate an oxocarbenium-like intermediate upon activation. Activation is achieved with electrophilic promoters that convert the C1–S bond into a better leaving group, enabling glycosylation with various acceptors.

Common activation methods involve electrophilic halogen donors such as N-iodosuccinimide (NIS) in combination with a Lewis acid like TfOH (triflic acid) or with AgOTf, as well as other promoters like TMSOTf. These conditions facilitate formation of the glycosyl donor intermediate and subsequent coupling to form new glycosidic bonds under controlled stereochemical outcomes.

Preparation of thioglycosides typically starts from a reducing sugar and a thiol (for example, thiophenol or other thiols) or via conversion of a hemiacetal to a thioglycoside using appropriate thio reagents. They include S-phenyl, S-benzyl, and other aryl or alkyl thioglycosides derived from common hexoses and pentoses.

In summary, thioglycosides are key versatile intermediates for assembling complex carbohydrates, offering stability and tunable reactivity that support selective, stereocontrolled glycosylation.