Multivalent 1,2,3-Triazole-Linked Carbohydrate Mimetics by Huisgen-Meldal-Sharpless Cycloadditions of an Azidopyran

Starting from an enantiopure 3-azido-substituted pyran derivative and various oligo-alkynes a series of multivalent 1,2,3-triazole-linked carbohydrate mimetics was synthesized. The copper-catalyzed Huisgen-Meldal-Sharpless cycloaddition (CuAAC) served as key coupling reaction. Cu/C in the presence of triethylamine proved to be a good catalytic system in most cases. Tri-, tetra-, hexa-, and octavalent compounds with typical rigid or flexible core units were prepared. The most complex compound contains a C-60-fullerene center leading to a dodecavalent carbohydrate mimetic. Only a few of the multivalent target compounds could be converted into pure O-sulfated derivatives that are required for their evaluation as L- and P-selectin ligands. Nevertheless, preliminary experiments suggest that the dodecavalent C-60-derived compound may be a promising ligand of these biologically important proteins with IC50 values in the low nanomolar range.