Jan Arnarp

Synthesis of a tri-, a penta-, and a hepta-saccharide containing terminal N-acetyl-β-D-lactosaminyl residues, part of the ‘complex-type’ carbohydrate moiety of glycoproteins

Silver trifluoromethanesulphonate-promoted condensation of 3,6-di-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-2-deoxy-2-phthalimido-β-D-glucopyranosyl bromide with benzyl 3-O-benzyl-4,6-O-benzyl-idene-α-D-mannopyranoside, benzyl 3,6-di-O-benzyl-α-D-mannopyranoside, and benzyl 3,6-di-O-(3,4,6-tri-O-benzyl-α-D-mannopyranosyl)-2,4-di-O-benzyl-α-D-mannopyranoside gave the protected tri-, penta-, and heptasaccharide derivatives in 66, 72, and 56% yields, respectively. The free oligosaccharides were obtained after exchanging of the 2-deoxy-2-phthalimido-groups for 2-acetamido-2-deoxy-groups and deblocking.

Synthesis of three oligosaccharides that form part of the complex type of carbohydrate moiety of glycoproteins

Silver trifluoromethanesulfonate-promoted condensation of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl bromide with benzyl 3,6-di-O-benzyl-alpha-D-mannopyranoside and benzyl 3,4-di-O-benzyl-alpha-D-mannopyranoside gave the protected 2,4- and 2,6-linked trisaccharides in yields of 54 and 32%, respectively. After exchanging the 2-deoxy-2-phthalimido groups for 2-acetamido-2-deoxy groups and de-blocking, the trisaccharides 2,4-di-O-(2-deoxy-beta-D-glucopyranosyl)-D-mannose and 2,6-di-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-D-mannose were obtained. Similar condensation of 3,6-di-O-acetyl-2-deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-beta-D-glucopyranosyl bromide with benzyl 3,4-di-O-benzyl-alpha-D-mannopyranoside gave a pentasaccharide derivative in 52% yield. After transformations analogous to those applied to the trisaccharides, 2,6-di-O-[beta-D-galactopyranosyl-(1 leads to 4)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)]-D-mannose was obtained.

Synthesis of hepta- and penta-saccharides, part of the complex-type carbohydrate portion of glycoproteins

Silver trifluoromethanesulphonate-promoted condensation of 3,6-di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-2-deoxy-2-phthalimido-β-D-mannopyranoside and benzyl 2,4-di-O-benzyl-3,6-di-O-(3,4,6,-tri-O-benzyl-α-D-mannopyranosyl)-α-D-mannopyranoside gave a protected pentasaccharide and a protected heptasaccharide in 56% and 43% yield, respectively; after deblocking the free penta- and heptasaccharides were obtained.

Synthesis of a nonasaccharide containing terminal N-acetyl-β-D-lactosaminyl residues, part of the ‘complex-type’ carbohydrate moiety of glycoproteins

Silver trifluoromethanesulphonate-promoted condensation of 3,6-di-O-acetyl-2-deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-β-D-glucopyranosyl bromide with benzyl O-(3,6-di-O-benzyl-α-D-mannopyranosyl)-(1 → 3)-O-[3,4,6-tri-O-benzyl-α-D-mannopyranosyl-(1 → 6)]-2,4-di-O-benzyl-α-D-mannopyranoside gave a protected nonasaccharide derivative in 19% yield. The free oligosaccharide was obtained after exchanging the 2-phthalimido-groups for 2-acetamido-groups and deblocking.

Synthesis of three oligosaccharides that form part of the complex type of carbohydrate moeity of glycoproteins containing intersecting N-acetylglucosamine

The oligosaccharides (1)–(3) have been synthesized by conventional methods. 4-O-(2-Acetamido-2-deoxy-β-D-glucopyranosyl)-3,6-di-O-(α-D-mannopyranosyl)-D-mannose (1), 4-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-3,6-bis-O-[2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-D-mannopyranosyl]-D-mannose (2), and 3,6-bis-O-{2-O-[2-acetamido-2-deoxy-4-O-(β-D-galacto-pyranosyl)-β-D-glucopyranosyl]-α-D-mannopyranosyl}-4-O-(2-acetamido-2-deoxy-β-D-glucopy-ranosyl)-D-mannose (3) represent partial structures of the carbohydrate moiety in those glycoproteins of the complex type in which a 2-acetamido-2-deoxy-β-D-glucopyranosyl group is linked to O-4 of the β-D-mannopyranosyl residue of the invariant core (4). p-Methoxybenzyl groups were used for temporary protection of hydroxy groups