Synthesis of Thiohydantoin-Castanospermine Glycomimetics as Glycosidase Inhibitors

摘要

The preparation of bicyclic carbohydrate mimics related to(+)-castanospermine incorporating a thiohydantoin moietyis reported. The synthetic approach is compatible withmolecular diversity-oriented strategies and involves a-azi-doesters, built at the C-5/C-6 segment in gluco- or galacto-furanose scaffolds, as the key precursors. Reduction to thecorresponding a-amino ester and in situ coupling withisothiocyanates afford thioureidoester intermediates thatundergo spontaneous cyclization to the corresponding hy-dantoins, β-elimination, and furanose →indolizidine rear-rangement in a tandem manner. Biological evaluation of thenew sp~2-iminosugar-type glycomimetics evidenced a stronginfluence of the nature of the substituents at the nitrogen oroxygen atoms on the glycosidase inhibitory properties.