Synthesis of a neoglycoprotein containing the Lewis X analogous trisaccharide β- d-Gal pNAc-( [formula omitted]4)[ α- l-Fuc p-( [formula omitted]3)]- β- d-Glc pNAc

Abstract

The trisaccharide allyl glycoside 36 and related disaccharide part structures have been prepared using the 2-trichloroacetamido-2-deoxy- α- d-galactopyranosyl trichloroacetimidate derivative 9 as glycosyl donor under promotion with TMSOTf or Sn(OTf) 2, respectively, to produce the β-( 1 → 4) linkage to suitably protected glucosamine derivatives in fair yields. Fucosylation was effected employing the ethyl 1-thio glycosyl donor 20 in the presence of IDCP. Deprotection of the intermediates afforded the disaccharide allyl glycosides β- d-Gal pNAc-( 1 → 4)- β- d-Glc pNAc 13, β- d-Gal pNClAc-( 1 → 4)- β- d-Glc pNAc 14, α- l-Fuc p-( 1 → 3)- β- d-Glc pNAc 24, α- l-Fuc p-( 1 → 4)- β- d-Glc pNAc 31 and the branched trisaccharide allyl glycoside β- d-Gal pNAc-( 1 → 4)[ α- l-Fuc p-( 1 → 3)]- β- d-Glc pNAc 36. The trisaccharide which corresponds to a structural motif occurring in N-glycoprotein glycans from human urokinase, human recombinant protein C, phospholipase A 2 as well as O-glycans, was converted into a neoglycoprotein following introduction of a cysteamine-derived spacer group and subsequent activation with thiophosgene.