Chemical Modification of Lactose. XIV. Synthesis of O-2-Acetamido-2-deoxy-β-D-glucopyranosyl-(1→3)-O-[2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→6)]-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranose (3', 6'-Di-β-N-acetylglucosaminyl-β-lactose)

Abstract

The title branched tetrasaccharide (18) is the core structure of more complex oligosaccharides of human milk. A synthesis of 18 was achieved. Stirring of the acetylated oxazoline derivative of GlcNAc (6 mol eq.), 1, 6-anhydro-2, 2', 3, 4'-tetra-O-benzyl-β-lactose (7, 1 mol eq.), and p-toluenesulfonic acid in 1, 2-dichloroethane at 60-65°for 48 hr under nitrogen afforded products consisting of the corresponding tetrasaccharide (major) contaminated with by-products and trisaccharide (minor). The former was purified by debenzylation followed by acetylation to isolate the desired tetrasaccharide as the acetylated 1, 6-anhydro-β-derivative (15) in 81.7% yield based on 7. The protecting groups of 15 were removed by acetolysis and de-O-acetylation, and 18 was obtained as hygroscopic fine needles in 69% yield from 15. The latter was isolated in 16% yield by column chromatography and assigned as O-2-acetamido-3, 4, 6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl-(1→6)-O-2, 4-di-O-benzyl-β-D-galactopyranosyl-(1→4)-1, 6-anhydro-2, 3-di-O-benzyl-β-D-glucopyranose.