Synthesis of hyaluronic acid-related di-, tri-, and tetra-saccharides having an N-acetylglucosamine residue at the reducing end

Ted M. Slaghek*, Yoshiaki Nakahara, Tomoya Ogawa, Johannis P. Kamerling, Johannes F.G. Vliegenthart

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Scopus)

Abstract

The synthesis is reported of 4-methoxyphenyl O-(β-d-glucopyranosyluronic acid)-(1 → 3)-2-acetamido-2-deoxy-β-d-glucopyranoside (1), 4-methoxyphenyl O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-O-(β-d-glucopyranosyluronic acid)-(1 → 3)-2-acetamido-2-deoxy-β-d-glucopyranoside (5), and 4-methoxyphenyl O-(β-d-glucopyranosyluronic acid)-(1 → 3)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-O-(β-d-glucopyranosyluronic acid)-(1 → 3)-2-acetamido-2-deoxy-β-d-glucopyranoside (10), which are structural elements of the extracellular polysaccharide hyaluronic acid. 6-O-Levulinoyl-2,3,4-tri-O-p-toluoyl-α-d-glucopyranosyl trichloroacetimidate (3) was condensed with 4-methoxyphenyl 2-deoxy-4,6-O-isopropylidene-2-phthalimido-β-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-β-d-glucopyranosyl)-(1 → 3)-4,6-di-O-acetyl-2-deoxy-2-phthalimido-β-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-α-d-glucopy ranosyl trichloroacetimidate 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-β-d-glucopyranosyl trichloroacetimidate with 8 afforded trisaccharide derivative 4-methoxyphenyl O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1 → 4)-O-(6-O-levulinoyl-2,3-di-O-p-toluoyl-β-d-glucopyranosyl)-(1 → 3)-4,6-di-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranoside, and subsequent delevulinoylation, oxidation, complete deprotection, and N-acetylation gave 5. 3-O-Allyloxycarbonyl-2-deoxy-4,6-O-isopropylidene-2-phthalimido-β-d -glucopyranosyl tricholoroacetimidate 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-β-d-glucopyranosyl)-(1 → 3)-O-(4,6-di-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1 → 4)-O-(6-O-levulinoyl-2,3-di-O-p-toluoyl-β-d-glucopyranosyl)-(1 → 3)-4,6-di-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranoside, and delevulinoylation, oxidation, complete deprotection, and N-acetylation yielded 10.

Original languageEnglish
Pages (from-to)61-85
Number of pages25
JournalCarbohydrate Research
Volume255
Issue numberC
DOIs
Publication statusPublished - 4 Mar 1994
Externally publishedYes

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