Synthesis of sulfated trisaccharide ligands for the selectins

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): Gal beta 1-->3(Fuc alpha 1-->4)GlcNAc] and Lewis x [Le(x): Gal beta 1-->4(Fuc alpha 1-->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 beta-allyl aglycone, providing a single anomer of each final product and allowing for further modification into multivalent derivatives. (C) 1997 Elsevier Science Ltd.