Synthesis of a fucosylated and a non-fucosylated core structure of xylose-containing carbohydrate chains from N-glycoproteins

The synthesis is reported of methyl 2-acetamido-4-O-[2-acetamido-2-deoxy-4-O-(3,6-di-O-α-D-mannopyranosyl-2-O-β-D -xylopyranosyl-β-D-mannopyranosyl)-β- D-glucopyranosyl]-2-deoxy-β-D-glucopyranoside (4) and methyl 2-acetamido-4-O-[2-acetamido-2-deoxy-4-O-(3,6-di-O-α-D-mannopyranosyl-2-O-β-D -xylopyranosyl-β-mannopyranosyl)-β- D-glucopyranosyl]-2-deoxy-6-O-α-L-fucopyranosyl-β-D- glucopyranoside (5), which represent the invariant hexasaccharide core structure of the xylose-containing glycans of N-glycoproteins and its 6-O-fucosylated derivative. Ethyl 4-O-[3-O-allyl-4-O-benzoyl-6-O-tert-butyldimethylsilyl-2-O-(2,3,4-tri-O-acetyl -β- D-xylopyranosyl)-β-D-mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2-phthalimido-1 -thio-β-D-glucopyranoside (9) was coupled with methyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β- D-glucopyranoside (11). Desilylation of the resulting tetrasaccharide derivative, followed by condensation with 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl trichloroacetimidate (7), gave methyl 4-O-{4-O-[3-O-allyl-4-O-benzoyl-6-O-(2,3,4,6-tetra-O-acetyl-α-D -mannopyranosyl)-2-O-(2,3,4-tri-O-acetyl-β- D-xylopyranosyl)-β-D-mannopyranosyl] -3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl}-3,6-di-O-benzyl-2 -deoxy-2-phthalimido-β-D-glucopyranoside (14). Deallylation of 14, followed by condensation with 7 and deprotection, gave hexasaccharide 4. Ethyl 3,6-di-O-benzyl-2-deoxy-4-O-[4,6-di-O-acetyl-3-O-allyl-2-O-(2,3,4-tri-O-acetyl -β-D-xylopyranosyl)-β-D-mannopyranosyl] -2-phthalimido-1-thio-β-D-glucopyranoside (17) was coupled with methyl 3-O-benzyl-2-deoxy-6-O-(4-methoxybenzyl)-2-phthalimido-β- D-glucopyranoside. Demethoxybenzylation of the tetrasaccharide derivative thus obtained, followed by fucosylation using ethyl 2,3,4-tri-O-benzyl-1-thio-β-L-fucopyranoside, gave methyl 3-O-benzyl-2-deoxy-4-O-{3,6-di-O-benzyl-2-deoxy-4-O-[4,6-di-O-acetyl-3-O-allyl -2-O-(2,3,4-tri-O-acetyl-β-D-xylopyranosyl)-β-D-mannopyranosyl]-2-phthalimido -β- D-glucopyranosyl}-2-phthalimido-6-O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-β - D-glucopyranoside (23). 0-Deacetylation followed by tert-butyldimethylsilylation, benzoylation, and desilylation gave methyl 4-O-{4-O-[3-O-allyl-4-O-benzoyl-2-O-(2,3,4-tri-O-benzoyl-β- D-xylopyranosyl)-β-D-mannopyranosyl] -3,6-di-O-benzyl-2-deoxy-2-phthalimido-β- D-glucopyranosyl}-3-O-benzyl-2-deoxy-2-phthalimido-6-O-(2,3,4-tri-O-benzyl-α -L-fucopyranosyl)-β-D-glucopyranoside (24). Mannosylation of 24 using 7, followed by deallylation, further mannosylation with 7, and deprotection, gave the heptasaccharide 5.