Chemical and Enzymatic Synthesis of Modified Sialyl Lewis X Tetrasaccharides with High Affinity for E and P‐Selectin

A series of sialyl-Lewis X tetrasaccharide analogs 1a—d was prepared using a combined chemical and enzymatic approach. Sialic acid analogs 5b,c were obtained from 2-azido mannose 4c or 2-deoxy mannose 4b and pyruvate by an aldolase reaction and converted to the protected thioglycosides 3b,c that served as sialyl donors for the Lewis X acceptor trisaccharide 2. The resulting sialyl-Lewis X tetrasaccharides 8a—c were deprotected by deacylation and saponification of the methyl ester. Debenzylation was achieved by careful transfer hydrogenation in the presence of formic acid or ammonium formate as a hydrogen source. Three sialyl-Lewis X derivatives 1a—c were thus obtained and the parent compound 1a was further modified by alkaline hydrolysis of the two acetamides to give the lyso sialyl-Lewis X derivative 1d. The four sialyl-Lewis X tetrasaccharides 1a—d were tested for their binding affinity to E and P-selectin with the lyso sialyl-Lewis X derivative 1d showing the highest inhibitory potency for both lectins.