Synthesis of 2-acetamido-2-deoxy-4-O-(2-O-methyl-β-D-galactopyranosyl)-d-glucopyranose (N-acetyl-2′-O-methyllactosamine)

1,3,4,6-Tetra-O-acetyl-2-O-methyl-d-galactopyranose, prepared from known methyl 6-O-acetyl-3,4-O-isopropylidene-β-d-galactopyranoside, was treated with hydrogen bromide in dichloromethane to afford 3,4,6-tri-O-acetyl-2-O-methyl-α-d-galactopyranosyl bromide. Condensation with benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-d-glucopyranoside in acetonitrile in the presence of mercuric cyanide gave an approximately 1:1 mixture of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(3,4,6-tri-O-acetyl-2-O-methyl-β- (8) and -α-d-galactopyranosyl)-α-d-glucopyranoside. O-Deacetylation and catalytic hydrogenolysis of the benzyl group furnished 2-acetamido-2-deoxy-4-O-(2-O-methyl-β- and α-d-galactopyranosyl)-d-glucopyranose. Alternatively, benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-d-galactopyranosyl-α-d-glucopyranoside was treated with tert-butyldiphenyl-chlorosilane in N,N-dimethylformamide, in the presence of imidazole, to give a 6′-O-tert-butyldiphenylsilyl intermediate that was in turn converted into its 3′,4′-O-isopropylidene acetal. Methylation with methyl iodide-silver oxide in N,N-dimethylformamide, followed by removal of the silyl and isopropylidene groups gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(2-O-methyl-β-d-galactopyranosyl)-α-d-glucopyranoside, which was further characterized as its triacetate 8.