A highly practical synthesis of the sialyl Lewis X pentasaccharide and an investigation of binding to E-, P-, and L-selectins.

A practical synthesis of the sialyl Lewis X (sLex) pentasaccharide, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta OEt (1), as a potential blocker for E-selectin has been described. The glycosylation of a trisaccharide acceptor, Fuc alpha (1-3)GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, did not yield the desired sLex pentasaccharide 1 at all. However, the glycosylation of a disaccharide acceptor, GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, quantitatively yielded the tetrasaccharide NeuAc alpha (2-3)Gal beta (1-4)GlcNAc beta (1-3)Gal beta OEt. This tetrasaccharide is readily converted to the title compound in a high yield by fucosylation, followed by deprotection. The inhibitory activities of compound 1 toward the binding of the natural ligand (sLex) with the E-, P-, and L-selectins were stronger than those of the sLex tetrasaccharide.