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

D Goyard (1) , Michel Baron , Pv Skourti , As Chajistamatiou , T Docsa , P Gergely , Ed Chrysina , Jp Praly (1) , S. Vidal (1)

1 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires

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.

Domaines: Chimie organique; Biochimie [q-bio.BM]

D Goyard, Michel Baron, Pv Skourti, As Chajistamatiou, T Docsa, et al.. 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, 364, pp.28-40. ⟨10.1016/j.carres.2012.09.020⟩. ⟨hal-01319089⟩