Synthesis of Thiohydantoin-Castanospermine Glycomimetics as Glycosidase Inhibitors

被引：23

作者：

Aguilar-Moncayo, Matilde ^{[1
]}

Ortiz Mellet, Carmen ^{[1
]}

Garcia Fernandez, Jose M. ^{[2
]}

Isabel Garcia-Moreno, M. ^{[1
]}

机构：

[1] Univ Seville, Dept Quim Organ, Fac Quim, E-41012 Seville, Spain

[2] Univ Seville, Inst Invest Quim, CSIC, E-41092 Seville, Spain

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2009年 / 74卷 / 09期

关键词：

SUGAR AMINO-ACIDS; GLYCOGEN PHOSPHORYLASES; INDOLIZIDINE; NUCLEOSIDES; METABOLITE; BINDING;

D O I：

10.1021/jo900231b

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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 (x-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.

引用

页码：3595 / 3598

页数：4

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