Protected Trisaccharide Research Articles

Synthesis of p-nitrophenyl 2-acetamido-2-deoxy-4- O-β- d-galactopyranosyl- β- d-glucopyranoside, and p-nitrophenyl 6- O-(2-acetamido-2-deoxy-3- O- and -4- O-β- d-galactopyranosyl- β- d-glucopyranosyl)-α- d-mannopyranoside

A facile synthesis of p-nitrophenyl 2-acetamido-2-deoxy-4- O-β- d-galactopyranosyl- β- d-glucopyranoside was accomplished by saponification of the product obtained by reaction of 2-acetamido-3,6-di- O-acetyl-2-deoxy-4- O-(2,3,4,6-tetra- O-acetyl- β- d-galactopyranosyl)-α- d-glucopyranosyl chloride and Amberlyst A-26 p-nitrophenoxide. The reaction of p-nitrophenyl 2,3- O-isopropylidene-α- d-mannopyranoside ( 7) with the easily accessible 2-methyl-[4,6-di- O-acetyl-2-deoxy-3- O-(2,3,4,6-tetra- O- acetyl-β- d-galactopyranosyl)-α- d-glucopyrano]-[2,1- d]-2-oxazoline proceeded readily, to give the protected trisaccharide derivative which, on deacetonation, followed by O-deacetylation, produced one of the title trisaccharides, namely, p-nitrophenyl 6- O-(2-acetamido-2-deoxy-3- O-β- d-galactopyranosyl-β- d-glucopyranosyl)-α- d-mannopyranoside. Synthesis of the other trisaccharide, p-nitrophenyl 6- O-(2-acetamido- 2-deoxy-4- O-β- d-galactopyranosyl-β- d-glucopyranosyl)-α- d-mannopyranoside was accomplished by a similar reaction-sequence when the corresponding 2-methyl-[3,6- di- O-acetyl-2-deoxy-4- O-(2,3,4,6-tetra- O-acetyl-β- d-galactopyranosyl)-α- d-glucopyrano]- [2,1- d]-2-oxazoline ( 19) reacted with 7. Preparation of oxazoline 19 was achieved via acetolysis of methyl 2-acetamido-2-deoxy-4- O-β- d-galactopyranosyl-α- d-glucopyranoside. The structures assigned to the final saccharides were supported by 1H- and 13C-n.m.r.-spectral data.

Synthesis of O-β-D-galactopyranosyl-(1→4)-O-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→3)-D-mannose, a postulated trisaccharide of human erythrocyte membrane sialoglycoprotein

Monoallylation of tributylstannylated benzyl 6-O-trityl-α-D-mannopyranoside (3) was efficiently catalysed by tetrabutylammonium bromide to give the 3-O-(4) and 2-O-(5) allyl ethers in 62 and 15% yields, respectively. Compound (4) was converted into crystalline benzyl 3-O-allyl-2,4-di-O-benzyl-α-D-mannopyranoside (10), which was then isomerized, allylated, and hydrolysed to give benzyl 6-O-allyl-2,4-di-O-benzyl-α-D-mannopyranoside (11). This compound was condensed with the oxazoline (12), derived from D-lactosamine, to give the protected trisaccharide (13) in 9% yield. Removal of the protecting groups gave the free trisaccharide β-D-Gal-(1→4)-β-D-GlcNAc-(1→3)-D-Man (15). The carbohydrate sequence of this trisaccharide has been postulated in some membrane glycoproteins and will be tested for its li blood group activity.

Studies in oligosaccharide chemistry. Part 8. Synthesis of lacto-N-triose I, a core chain trisaccharide of human blood-group substances

Condensation of 4,6-di-O-acetyl-1,2-dideoxy-2′-methyl-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-glucopyranoso[2,1-d]-Δ2′-oxazoline (4) with benzyl 6-O-allyl-2,4-di-O-benzyl-α-D-galactopyranoside (5) in the presence of toluene-p-sulphonic acid gave a protected trisaccharide (6) in 84% yield. Removal of the protecting groups gave the free trisaccharide β-D-Gal-(1 → 3)-β-D-GlcNAc-(1 → 3)-D-Gal (10), identical in properties with ‘Lacto-N-triose-I,’ a product of acidic hydrolysis of carbohydrates from human milk and blood-group substances. The carbohydrate sequence of the trisaccharide (10) is representative of the ‘core’ portion of blood-group substances.