title: Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: evaluation of the xylose scaffold for the design of potential glycogen phosphorylase inhibitors.
abstract: Various acetylenic derivatives and acetylated β-D-xylopyranosyl azide or the 5-thio-β-d-xylopyranosyl analogue were coupled by Cu(I)-catalyzed azide alkyne 1,3-dipolar cycloaddition (CuAAC) to afford a series of 1-xylosyl-4-substituted 1,2,3-triazoles. Controlled oxidation of the endocyclic sulfur atom of the 5-thioxylose moiety led to the corresponding sulfoxides and sulfones. Deacetylation afforded 19 hydroxylated xylose and 5-thioxylose derivatives, found to be only sparingly water-soluble. Compared to glucose-based analogues, they appeared to be much weaker inhibitors of glycogen phosphorylase, as the absence of a hydroxymethyl group weakens their binding at the enzyme active site. However, such new xylose derivatives might be useful glycomimetics.
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2, Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France.
authors.forename: David
authors.initials: D
authors.lastname: Goyard
authors.forename: Marc
authors.initials: M
authors.lastname: Baron
authors.forename: Paraskevi V
authors.initials: PV
authors.lastname: Skourti
authors.forename: Aikaterini S
authors.initials: AS
authors.lastname: Chajistamatiou
authors.forename: Tibor
authors.initials: T
authors.lastname: Docsa
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
authors.forename: Evangelia D
authors.initials: ED
authors.lastname: Chrysina
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Praly
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vidal
mesh_terms: D000107:Acetylation; D000480:Alkynes / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry; D020134:Catalytic Domain; D061565:Cycloaddition Reaction / Q000379:methods; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D005947:Glucose / Q000031:analogs & derivatives / Q000737:chemistry; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006006:Glycogen Synthase / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D011485:Protein Binding; D012995:Solubility; D013237:Stereoisomerism; D013454:Sulfoxides / Q000737:chemistry; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry; D014867:Water / Q000737:chemistry; D014994:Xylose / Q000737:chemistry*
chemical_list: D000480:Alkynes; D004791:Enzyme Inhibitors; D013454:Sulfoxides; D014230:Triazoles; D014867:Water; C003002:5-thio-D-glucose; C098108:N-acetylglucopyranosylamine; D014994:Xylose; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase; D005947:Glucose; D005944:Glucosamine