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.

David Goyard, Marc Baron, Paraskevi V Skourti, Aikaterini S Chajistamatiou, Tibor Docsa, Pál Gergely, Evangelia D Chrysina, Jean-Pierre Praly, Sébastien Vidal

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.

Carbohydrate research 2012 Dec 15

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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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

David Goyard, Marc Baron, Paraskevi V Skourti, Aikaterini S Chajistamatiou, Tibor Docsa, Pál Gergely, Evangelia D Chrysina, Jean-Pierre Praly, Sébastien Vidal. 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. Carbohydrate research. 2012 Dec 15;364:28-40