Remove to improve. Removal of the hydroxymethyl groups in 1 to give 2 significantly enhances inhibitory potency towards glucosylceramide β‐glucosidase (GCase) and abolishes inhibition towards α‐glucosidases. Xylitol 2 doubles the residual activity of GCase in fibroblasts from Gaucher patients at subinhibitory concentration (10 nM). This compound is therefore a promising candidate for the development of small‐molecule drugs for the treatment of Gaucher's disease without the side effects associated with α‐glucosidase inhibition.

In contrast to most lectins, glycosidases may appear to be unpromising targets for multivalent binding because they display only a single active site. To explore the potential of multivalency on glycosidase inhibition, unprecedented cyclodextrin-based iminosugar conjugates have been designed and prepared. The synthesis was performed by way of Cu(I) -catalyzed azide-alkyne cycloaddition reaction under microwave activation between propargylated multivalent β-cyclodextrins and an azide-armed N-alkyl 1-deoxynojirimycin derivative. Evaluation with a panel of glycosidases of this new class of glycomimetic clusters revealed the strongest affinity enhancement observed to date for a multivalent glycosidase inhibitor, with binding enhancement up to four orders of magnitude over the corresponding monovalent ligand for α-mannosidase. These results demonstrate that the multivalency concept extends beyond carbohydrate-lectin recognition processes to glycomimetic-enzyme inhibition.