Synthetic Studies on Sialoglycoconjugates. CXXIV. Total Synthesis of O-Glycan on the L-Selectin Ligand GlyCAM-1

Abstract

The total synthesis of O-glycans containing the sulfated sialyl Le^x (sLe^x) determinant on GlyCAM-1 (1), the counter-receptor glycoprotein for L-selectin, was accomplished by a simultaneous glycosylation procedure. The glycosylation of the lactoside acceptor (4) with the 2-azidogalactopyranosyl trichloroacetimidate donor (3) resulted in the desired trisaccharide (5). This trisaccharide, after transformation to the glycosyl acceptor, was successfully coupled with the phenylthioglycoside of glucosamine (13) to give the core 6 structure (14). Following proper manipulation of the protecting groups for the hydroxyl, as well as the amino function, the resulting free hydroxyl of the tetrasaccharide at C3 of the GlcNAc was then fucosylated to give the desired pentasaccharide (19). This pentasaccharide was converted into the key glycosyl acceptor (21), which was then simultaneously glycosylated with the sialyl α (2→3)-galactosyl trichloroacetimidate (22), forming the desired nonasaccharide (23). Finally, sulfation of the 6-OH of the GlcNAc residue and removal of all the protecting groups furnished the spacer-armed O-glycans on GlyCAM-1 (1).