Synthesis of thiohydantoin-castanospermine glycomimetics as glycosidase inhibitors.
The preparation of bicyclic carbohydrate mimics related to (+)-castanospermine incorporating a thiohydantoin moiety is reported. The synthetic approach is compatible with molecular diversity-oriented strategies and involves alpha-azidoesters, built at the C-5/C-6 segment in gluco- or galactofuranose scaffolds, as the key precursors. Reduction to the corresponding alpha-amino ester and in situ coupling with isothiocyanates afford thioureidoester intermediates that undergo spontaneous cyclization to the corresponding hydantoins, beta-elimination, and furanose --> indolizidine rearrangement in a tandem manner. Biological evaluation of the new sp(2)-iminosugar-type glycomimetics evidenced a strong influence of the nature of the substituents at the nitrogen or oxygen atoms on the glycosidase inhibitory properties.
Aguilar-Moncayo
Matilde
M
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, E-41012 Sevilla, Spain.
Mellet
Carmen Ortiz
CO
García Fernández
José M
JM
García-Moreno
M Isabel
MI