Synthesis of a Mannose-Bearing Disaccharide with a Thiol Spacer at the Reducing End

Abstract

The synthesis of a mannose-bearing disaccharide containing a thiol spacer at the reducing end was carried out to provide a tethered sugar suitable for attaching to gold nanoparticles. An array of such sugars is designed to mimic carbohydrates involved in cell-surface interactions. The molecule was constructed via Schmidt glycosylation of an appropriately protected glycosyl donor and an acceptor, followed by removal of protective groups and reductive amination to introduce a protected thiol spacer at the reducing end of the glycan. A new finding that the anomeric reductive amination is capable of concomitantly removing a neighboring N-acetyl group was also observed. Subsequent removal of the thiol protective group and purification of the product gave the target disaccharide in a satisfactory yield. Keywords: Carbohydrate, oligosaccharide, glycosylation, mannose, nanoparticle, thiol, biomineralization, cytotoxicity, globular