The 2-Naphthylmethyl (NAP) Group in Carbohydrate Synthesis: First Total Synthesis of the GlyCAM-1 Oligosaccharide Structures

Abstract

Total syntheses of the GlyCAM-1 (glycosylation-dependent cell adhesion molecule-1) oligosaccharide structures: {α-NeuAc-(2→3)-β-Gal-(1→4)-[α-Fuc-(1→3)]-β-(6-O-SO3Na)-GlcNAc-(1→6)}-[α-NeuAc-(2→3)-β-Gal-(1→3)]-α-GalNAc-OMe (1) and {α-NeuAc-(2→3)-β-Gal-(1→4)-[α-Fuc-(1→3)]-β-GlcNAc-(1→6)}-[α-NeuAc-(2→3)-β-Gal-(1→3)]-α-GalNAc-OMe (2) through a novel sialyl Lewisx tetrasaccharide donor are described. Employing sequential glycosylation strategy, the starting trisaccharide was regio- and stereoselectively constructed through coupling of a disaccharide imidate with the monosaccharide acceptor phenyl-6-O-naphthylmethyl-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside with TMSOTf as a catalyst without affecting the SPh group. The novel sialyl Lewisx tetrasaccharide donor 3 was then obtained by α-L-fucosylation of trisaccharide acceptor with the 2,3,4-tri-O-benzyl-1-thio-β-L-fucoside donor. The structure of the novel sialyl Lewisx tetrasaccharide was established by a combination of 2D DQF-COSY and 2D ROESY experiments. Target oligosaccharides 1 and 2 were eventually constructed through heptasaccharide which was obtained by regioselective assembly of advanced sialyl Lewisx tetrasaccharide donor 3 and a sialylated trisaccharide acceptor in a predictable and controlled manner. Finally, target heptasaccharides 1 and 2 were fully characterized by 2D DQF-COSY, 2D ROESY, HSQC, HMBC experiments and FAB mass spectroscopy.