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 ß-D-GlcNAc, thus providing rapid access to attractive heteroglycosylated platforms for diverse biological applications.