Spiranic d-gluco-configured N-substituted thiohydantoins as potential enzymatic inhibitors

We have explored the preparation of conformationally-restricted pseudonucleosides bearing a spiranic thiohydantoin scaffold on C-3 of the sugar moiety by coupling partially protected 3-amino-3-methoxycarbonyl and 3-isothiocyanato-3-methoxycarbonyl glucofuranose derivatives with alkyl(aryl)isothiocyanates or with alkyl(aryl)amines; the key step is a spontaneous or thermal-induced intramolecular nucleophilic substitution of transient thioureas. Upon deprotection, final spiranic thiohydantoins were evaluated as glycosidase and glycogen phosphorylase inhibitors.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide