SOLUTION-PHASE AND SOLID-PHASE SYNTHESIS OF INHIBITORS OF HELICOBACTER-PYLORI ATTACHMENT AND E-SELECTIN-MEDIATED LEUKOCYTE ADHESION

Chemical and enzymatic methods have been developed for the synthesis of the oligosaccharides NeuAc alpha 2-->3Gal beta 1 -->4GlcNAc beta 1-->3Gal and NeuAc alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc beta 1-->3Gal as inhibitors for H. pylori and E-selectin, respectively. Gal, NeuAc, and Fuc were incorporated sequentially into the synthetic primer GlcNAc beta 1-->3Gal beta OEt 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 glycosylationl and the conversion for each step was found to be > 98% as indicated in the analysis of products released by treatment with hydrazine.