The 2-naphthylmethyl (NAP) group in carbohydrate synthesis: First total synthesis of the GlyCAM-1 oligosaccharide structures

Total syntheses of the Gly-CAM-1 (glycosylation-dependent cell adhesion mol ecule-1) oligosaccharide structures: {alpha -NeuAc-(2 --> 3)-beta -Gal-(1 - -> 4)-[alpha -Fuc-(1 --> 3)]-beta-(6-O-SO3Na)-GlcNac-(1 --> 6)}-[alpha -Neu Ac-(2 --> 3)-beta -Gal-(1 --> 3)]-alpha -GalNAc-OMe (1) and {alpha -NeuAc-( 2 --> 3)-beta -Gal-(1 --> 4)-[alpha -Fuc-(1 --> 3)]-beta -GlcNAc-(1 --> 6)} -[alpha -NeuAc-(2 --> 3)-beta -Gal-(1 --> 3)]-alpha -GalNAc-OMe (2) through a novel sialyl Lewis' tetrasaccharide donor are described. Employing seque ntial glycosylation strategy, the starting trisaccharide was regio- and ste reoselectively constructed through coupling of a disaccharide imidate with the monosaccharide acceptor phenyl-6-O-naphthylmethyl-2-deoxy-2-phthalimido -1-thio-beta -D-glucopyranoside with TMSOTf as a catalyst without affecting the SPh group. The novel sialyl Lewis(x) tetrasaccharide donor 3 was then obtained by alpha -L-fucosylation of trisaccharide acceptor with the 2,3,4- tri-O-benzyl-1-thio-beta -L-fucoside donor. The structure of the novel sial yl Lewis(x) 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 as sembly of advanced sialyl Lewis(x) tetrasaccharide donor 3 and a sialylated trisaccharide acceptor in a predictable and controlled manner. Finally, ta rget heptasaccharides 1 and 2 were fully characterized by 2D DQF-COSY: 2D R OESY, HSQC, HMBC experiments and FAB mass spectroscopy.