Synthesis of a neoglycoprotein containing the Lewis X analogous trisaccharide β-d-GalpNAc-(1→4)[α-l-Fucp-(1→3)]-β-d-GlcpNAc

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-GalpNAc-(1→4)-β-d-GlcpNAc 13, β-d-GalpNClAc-(1→4)-β-d-GlcpNAc 14, α-l-Fucp-(1→3)-β-d-GlcpNAc 24, α-l-Fucp-(1→4)-β-d-GlcpNAc 31 and the branched trisaccharide allyl glycoside β-d-GalpNAc-(1→4)[α-l-Fucp-(1→3)]-β-d-GlcpNAc 36. The trisaccharide which corresponds to a structural motif occurring in N-glycoprotein glycans from human urokinase, human recombinant protein C, phospholipase A2 as well as O-glycans, was converted into a neoglycoprotein following introduction of a cysteamine-derived spacer group and subsequent activation with thiophosgene.