Synthesis of Aminoethyl Glycosides of the Ganglioside GM₁ and Asialo-GM₁ Oligosaccharide Chains

Abstract

4′-O-Glycosylation of 2-azidoethyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O-benzyl-6-O-benzoyl-β-D-galactopyranosyl)-β-D-glucopyranoside with a disaccharide donor, 4-trichloroacetamidophenyl 4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-1-thio-2-trichloroacetamido-β-D-galactopyranoside, in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid resulted in a tetrasaccharide, 2-azidoethyl (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-(1 → 3)-(4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-β-D-galactopyranosyl)-(1 → 4)-(2,3-di-O-benzyl-6-O-benzoyl-β-D-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside, in 69% yield. The complete removal of O-protecting groups in the tetrasaccharide, the replacement of N-trichloroacetyl by N-acetyl group, and the reduction of the aglycone azide group to amine led to the target aminoethyl glycoside of β-D-Gal-(1 → 3)-β-D-GalNAc-(1 → 4)-β-D-Gal-(1 → 4)-β-D-Glc-OCH₂CH₂NH₂ containing the oligosaccharide chain of asialo-GM₁ ganglioside in 72% overall yield. Selective 3′-O-glycosylation of 2-azidoethyl 2,3,6-tri-O-benzyl-4-O-(2,6-di-O-benzyl-β-D-galactopyranosyl)-β-D-glucopyranoside with thioglycoside methyl (ethyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid afforded 2-azidoethyl [methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosyl)oate]-(2 → 3)-(2,6-di-O-benzyl-β-D-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside, the selectively protected derivative of the oligosaccharide chain of GM₃ ganglioside, in 79% yield. Its 4′-O-glycosylation with a disaccharide glycosyl donor, (4-trichloroacetophenyl-4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) 1-thio-2-trichloroacetamido-β-D-galactopyranoside in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid gave 2-azidoethyl (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-(1 → 3)-(4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-β-D-galactopyranosyl)-(1 → 4)-{[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosyl)onate]-(2 → 3)}-(2,6-di-O-benzyl-β-D-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside in 85% yield. The resulting pentasaccharide was O-deprotected, its N-trichloroacetyl group was replaced by N-acetyl group, and the aglycone azide group was reduced to afford in 85% overall yield aminoethyl glycoside of β-D-Gal-(1 → 3)-β-D-GalNAc-(1 → 4)-[α-D-Neu5Ac-(2 → 3)]-β-D-Gal-(1 → 4)-β-D-Glc-OCH₂CH₂NH₂ containing the oligosaccharide chain of GM₁ ganglioside.