Synthesis of Thiohydantoin-Castanospermine Glycomimetics as Glycosidase Inhibitors

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• 作者：Matilde Aguilar-Moncayo ; Carmen Ortiz Mellet ; Jos M. Garca Fernndez ; M. Isabel Garca-Moreno
• 刊名：Journal of Organic Chemistry
• 出版年：2009
• 出版时间：May 1, 2009
• 年：2009
• 卷：74
• 期：9
• 页码：3595-3598
• 全文大小：166K
• 年卷期：v.74,no.9(May 1, 2009)
• ISSN：1520-6904

文摘

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 α-azidoesters, built at the C-5/C-6 segment in gluco- or galactofuranose scaffolds, as the key precursors. Reduction to the corresponding α-amino ester and in situ coupling with isothiocyanates afford thioureidoester intermediates that undergo spontaneous cyclization to the corresponding hydantoins, β-elimination, and furanose → indolizidine rearrangement in a tandem manner. Biological evaluation of the new sp²-iminosugar-type glycomimetics evidenced a strong influence of the nature of the substituents at the nitrogen or oxygen atoms on the glycosidase inhibitory properties.