Synthesis of the spacer-containing β-d-GalpNAc-(1→4)-β-d-GlcpNAc-(1→3)-α-d-Galp moiety, representing the non-fucosylated backbone trisaccharide of the glycocalyx glycan of the parasite Schistosoma mansoni

The chemical synthesis of β-d-GalpNAc-(1→4)-β-d-GlcpNAc-(1→3)-α-d-Galp-(1→O)(CH2)5NH2 is described. This structure represents the nonfucosylated backbone trisaccharide of the glycocalyx glycan of the cercarial stage of the parasite Schistosoma mansoni. Synthesis of the trisaccharide was achieved via a stepwise coupling approach. 5-Azidopentyl 4-O-acetyl-2,6-di-O-benzyl-α-d-galactopyranoside was condensed with ethyl 6-O-benzyl-2-deoxy-3,4-di-O-dimethylisopropylsilyl-2-phthalimido-1-thio-β-d-glucopyranoside, using N-iodosuccinimide and silver trifluoromethanesulfonate as a catalyst system, followed by the removal of the silyl ether groups to afford a disaccharide acceptor. Coupling of ethyl 4,6-di-O-acetyl-3-O-allyloxycarbonyl-2-deoxy-2-phthalimido-1-thio-β-d-galactopyranoside to the disaccharide acceptor, using methylsulfenyl bromide and silver trifluoromethanesulfonate as a catalyst system, gave a protected trisaccharide. Deprotection of this compound yielded the target structure.