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

Abstract

A practical synthesis of the sialyl Lewis X (sLex) pentasaccharide, NeuAcα2–3Galβ1–4(Fucα-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 sLex 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 (sLex) with the E-, P-, and L-selectins were stronger than those of the sLex tetrasaccharide.