Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

Abstract

We describe the first one-pot orthogonal strategy to prepare well-defined cyclopeptide-based heteroglycoclusters (hGCs) from glycosyl thiols. Both thiol–chloroactetyl coupling (TCC) and thiol–ene coupling (TEC) have been used to decorate cyclopeptides regioselectively with diverse combination of sugars. We demonstrate that the reaction sequence starting with TCC can be performed one-pot whereas the reverse sequence requires a purification step after the TEC reaction. The versatility of this orthogonal strategy has been demonstrated through the synthesis of diverse hGCs displaying alternating binary combinations of α-D-Man or β-D-GlcNAc, thus providing rapid access to attractive heteroglycosylated platforms for diverse biological applications.

Keywords

• chemoselective ligation
• heteroglycocluster
• multivalency
• multivalent glycosystems
• one-pot synthesis