Synthesis of sulfated trisaccharide ligands for the selectins

Article abstract of DOI:10.1016/S0040-4020(97)01024-7

In a directed effort to elucidate the molecular factors responsible for selectin-mediated cell adhesion events as a basis for the generation of potent and specific inhibitors of these processes, we have synthesized a variety of sulfated analogs of the trisaccharide recognition epitopes Lewis a [Le^a: Ga1β1→3(Fucα1→4)GlcNAc] and Lewis x [Le(x): Galβ1→4(Fucαl→3)GlcNAc]. Our divergent synthetic route allows for the synthesis of gram quantities of these sulfated trisaccharides from common intermediates in 10-20% overall yields and in no more than 15 linear steps. In addition, we have anchored the reducing end of the Le^a and Le(x) trisaccharide precursors with a β- allyl aglycone, providing a single anomer of each final product and allowing for further modification into multivalent derivatives.