Synthesis of hyaluronic acid-related di-, tri-, and tetra-saccharides having an N-acetylglucosamine residue at the reducing end.
The synthesis is reported of 4-methoxyphenyl O-(beta-D-glucopyranosyluronic acid)-(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyranoside (1), 4-methoxyphenyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->4)-O-(beta-D- glucopyranosyluronic acid)-(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyranoside (5), and 4-methoxyphenyl O-(beta-D-glucopyranosyluronic acid)-(1-->3)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->4)-O-(b eta-D- glucopyranosyluronic acid)-(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyranoside (10), which are structural elements of the extracellular polysaccharide hyaluronic acid. 6-O-Levulinoyl-2,3,4-tri-O-p-toluoyl-alpha-D-glucopyranosyl trichloroacetimidate (3) was condensed with 4-methoxyphenyl 2-deoxy-4,6-O-isopropylidene-2-phthalimido-beta-D-glucopyranoside (4). De-isopropylidenation and acetylation of the obtained disaccharide derivative yielded 4-methoxyphenyl O-(6-O-levulinoyl-2,3,4-tri-O-p-toluoyl-beta-D-glucopyranosyl)-(1-->3)-4 ,6-di-O - acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside, and subsequent delevulinoylation, oxidation, complete deprotection, and N-acetylation gave 1. Coupling of 4-O-allyloxycarbonyl-6-O-levulinoyl-2,3-di-O-p-toluoyl-alpha-D-glu copyranosyl trichloroacetamidiate with 4 followed by de-isopropylidenation, acetylation, and deallyloxycarbonylation of the obtained disaccharide derivative gave 8. Condensation of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl trichloroacetimidate with 8 afforded trisaccharide derivative 4-methoxyphenyl O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1--> 4)-O-(6 - O-levulinoyl-2,3-di-O-p-toluoyl-beta-D-glucopyranosyl)-(1-->3)-4,6-di-O- acetyl- 2-deoxy-2-phthalimido-beta-D-glucopyranoside, and subsequent delevulinoylation, oxidation, complete deprotection, and N-acetylation gave 5. 3-O-Allyloxycarbonyl-2-deoxy-4,6-O-isopropylidene-2-phthalimido-be ta-D- glucopyranosyl trichloroacetimidate was coupled with disaccharide acceptor 8, and deallyloxycarbonylation of the obtained trisaccharide derivative yielded 12. Condensation of 3 with 12 followed by de-isopropylidenation and acetylation of the obtained tetrasaccharide derivative gave 4-methoxyphenyl O-(6-O-levulinoyl-2,3,4-tri-O-p-toluoyl-beta-D-glucopyranosyl)-(1-->3)-O -(4,6- di-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1-->4)-O-(6-O- levulinoyl-2,3-di-O-p-toluoyl-beta-D-glucopyranosyl)-(1-->3)-4,6-di-O-ac etyl-2- deoxy-2-phthalimido-beta-D-glucopyranoside, and delevulinoylation, oxidation, complete deprotection, and N-acetylation yielded 10.
Slaghek
T M
TM
Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, Netherlands.
Nakahara
Y
Y
Ogawa
T
T
Kamerling
J P
JP
Vliegenthart
J F
JF
D000117:Acetylglucosamine / Q000737:chemistry*; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis*; D006820:Hyaluronic Acid / Q000737:chemistry*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014312:Trisaccharides / Q000138:chemical synthesis*
D004187:Disaccharides; D009844:Oligosaccharides; D014312:Trisaccharides; D006820:Hyaluronic Acid; D000117:Acetylglucosamine