Odorless synthesis of thioglycosides using isothiouronium salts

Abstract

A practical and efficient method for the synthesis of thioglycosides has been developed using readily available isothiouronium salts as masked S-glycosylation reagents. Under optimized conditions, per-acetylated glycoside bromides were robustly converted into thioglycosides in moderate to good yields with exclusive stereoselectivity. By employing an increased dosage of TMG(1,1,3,3-tetramethylguanidine), a one-pot S-glycosylation–deacetylation process was achieved, affording deprotected thioglycosides in high yields. The methodology was successfully applied to a variety of monosaccharide substrates and demonstrated scalability to gram-scale reactions while maintaining efficiency. This approach represents an environmentally friendly alternative to conventional thioglycoside synthesis methods, overcoming the challenges of unpleasant odor and the limited availability of traditional thiol reagents.