Synthesis and glycosidase inhibition properties of triazole-linked calixarene–iminosugar clusters

• DOI: 10.1016/j.tet.2014.10.035
• Publication Date: 2014-10-22T16:34:21Z
• Authors: Alberto Marra; Renaud Zelli; Giuseppe D'Orazio; Barbara La Ferla; Alessandro Dondoni
• Keywords: Clusters; 1-Deoxynojirimycin derivatives; Calix[4]arenes, Clusters, 1-Deoxynojirimycin derivatives, Glycosidases inhibitors, Iminosugars; [CHIM] Chemical Sciences; Calix[4]arenes; Glycosidases inhibitors; Calix[4]arenes; Clusters; 1-Deoxynojirimycin derivatives; Glycosidases inhibitors; Iminosugars; Iminosugars; 01 natural sciences; 1-Deoxynojirimycin derivatives; Calix[4]arenas; Clusters; Glycosidases inhibitors; Iminosugars;; 0104 chemical sciences

Calixarene–iminosugar derivatives bearing four 1-deoxynojirimycin units at the upper or lower rim of calix[4]arenes in a fixed cone conformation were synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and their inhibitory activity was evaluated against five glycosidases. Modest but significant affinity enhancements of up to seven per 1-deoxynojirimycin unit over the monovalent iminosugar derivative were observed for the inhibition of Jack bean (Canavalia ensiformis) α-mannosidase. It was also demonstrated that the residual copper ions did not contribute to the inhibitory properties of the newly prepared calixarene-based multivalent iminosugars.