Solution- and solid-phase synthesis of inhibitors of H. pylori attachment and E-selectin-mediated leukocyte adhesion

Article abstract of DOI:10.1021/ja00104a011

Chemical and enzymatic methods have been developed for the synthesis of the oligosaccharides NeuAcα2 → 3Galβ1 → 4GlcNAcβ1 → 3Gal and NeuAcα2 → 3Galβ1 → 4(Fucα1 → 3)GlcNAcβ1 → 3Gal as inhibitors for H. pylori and E-selectin, respectively. Gal, NeuAc, and Fuc were incorporated sequentially into the synthetic primer GlcNAcβ1 → 3GalβOEt by the corresponding glycosyltransferases to give both the tetrasaccharide and the pentasaccharide. This solution-phase strategy was then extended to the solid-phase synthesis of the tetrasaccharide. A disaccharide primer was first attached to controlled pore glass via a spacer group containing an ester bond, followed by enzymatic incorporation of Gal and NeuAc. Two to three equivalents of sugar nucleotides were used in the enzymatic glycosylation, and the conversion for each step was found to be >98% as indicated in the analysis of products released by treatment with hydrazine.