Synthesis of O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-D- glucopyranose and two related trisaccharides containing the “lacto-N-biose II” unit

Abstract

Condensation of 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-acetyl-α-D-galactopyranosyl bromide (1) with benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside in boiling benzene and in the presence of mercuric cyanide afforded a trisaccharide that was O-deacetylated to give benzyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-β-D-galactopyranosyl-(1→4)-3,6-di-O-benzyl-2-deoxy -α-D-glucopyranoside, the benzyl groups of which were cleaved by catalytic hydrogenolysis to furnish the title trisaccharide. Alternatively, bromide 1 was allowed to react with 2-acetamido-1,6-anhydro-3-O-benzyl-2-deoxy-β-D-glucopyranose in 1:1 benzene-nitromethane in the presence of mercuric cyanide, followed by O-deacetylation, column chromatography, and reacetylation to give O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-acetyl-β-D- galactopyranosyl)-(1→4)-2-acetamido-1,6-anhydro-3-O-benzyl-2-deoxy-β-D-glucopyranose. Acetolysis, followed by catalytic hydrogenation and subsequent O-deacetylation furnished the title trisaccharide. A similar condensation of bromide 1 with 4-nitrophenyl 2-acetamido-2-deoxy-4,6-O-(4-methoxybenzylidene)-β-D-glucopyranoside and 2-nitrophenyl 2-acetamido-2-deoxy-4,6-O-(4-methoxybenzylidene)-α-D-galactopyranoside produced two trisaccharide derivatives, the acetal groups of which were cleaved in hot, 60% aqueous acetic acid, and the resulting diol intermediates O-deacetylated to furnish the desired trisaccharides 4-nitrophenyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-β-D-galactopyranosyl)-(1→3)-2- acetamido-2-deoxy-β-D-glucopyranoside and 2-nitrophenyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→3)-O-β-D-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D- galactopyranoside.