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 (sLe(x)) pentasaccharide, NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-3GalβOEt (1), as a potential blocker for E-selectin has been described. The glycosylation of a trisaccharide acceptor, Fucα(1-3)GlcNAcβ(1-3)GalβOEt, with a disaccharide donor, NeuAcα(2-3)GalβSMe, did not yield the desired sLe(x) pentasaccharide 1 at all. However, the glycosylation of a disaccharide acceptor, GlcNAcβ(1-3)GalβOEt, with a disaccharide donor, NeuAcα(2-3)GalβSMe, quantitatively yielded the tetrasaccharide NeuAcα(2-3)Galβ(1-4) GlcNAcβ(1-3)GalβOEt. 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 (sLe(x)) with the E-, P-, and L-selectins were stronger than those of the sLe(x) tetrasaccharide.