title: Synthesis of thiohydantoin-castanospermine glycomimetics as glycosidase inhibitors.
abstract: 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.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, E-41012 Sevilla, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Aguilar-Moncayo
authors.forename: Carmen Ortiz
authors.initials: CO
authors.lastname: Mellet
authors.forename: José M
authors.initials: JM
authors.lastname: García Fernández
authors.forename: M Isabel
authors.initials: MI
authors.lastname: García-Moreno