SYNTHESIS OF SULFATED TRISACCHARIDE LIGANDS FOR THE SELECTINS

In a directed effort to elucidate the molecular factors responsible fo r selectin-mediated cell adhesion events as a basis for the generation of potent and specific inhibitors of these processes, we have synthes ized a variety of sulfated analogs of the trisaccharide recognition ep itopes Lewis a [Le(a): Gal beta 1-->3(Fuc alpha 1-->4)GlcNAc] and Lewi s x [Le(x): Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc]. Our divergent synt hetic route allows for the synthesis of gram quantities of these sulfa ted 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 b eta-allyl aglycone, providing a single anomer of each final product an d allowing for further modification into multivalent derivatives. (C) 1997 Elsevier Science Ltd.