β-Thioglycosylation from Unactivated Carbohydrates

Area of Science:

• Carbohydrate Chemistry
• Organic Synthesis
• Medicinal Chemistry

Background:

• Thioglycosides are crucial in biology and drug discovery due to their unique properties.
• Stereoselective synthesis of thioglycosides from unactivated carbohydrates presents a significant challenge.

Purpose of the Study:

• To develop a novel S_N2 strategy for β-stereoselective thioglycosylation.
• To enable the synthesis of diverse thioglycosides using non-prefunctionalized glycosyl donors.

Main Methods:

• Employed an S_N2 strategy with anomeric non-prefunctionalized glycosyl donors.
• Utilized a designed thioglycosylating reagent with an iminium motif for in situ activation and acceptor integration.
• Facilitated reversible anomerization for stereospecific S_N2 coupling via an intimate ion pair.

Main Results:

• Achieved β-stereoconvergent thioglycosylation with high β-selectivity.
• Synthesized a library of 130 β-thioglycosides with diverse sp³-, sp²-, and sp-type sulfur acceptors.
• Demonstrated broad functional group compatibility and successful click linkage formation.

Conclusions:

• The developed S_N2 strategy offers an efficient route to β-thioglycosides.
• This method advances the synthesis of complex thioglycosides for drug discovery and bioconjugation.
• The strategy provides a versatile platform for creating novel carbohydrate-based molecules.