Synthesis and glycosidase inhibitory activity of aminocyclitols with a C6- or a C7-ring |
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| Authors: | Christine Gravier-PelletierWilliam Maton Thierry DintingerCharles Tellier Yves Le Merrer |
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| Affiliation: | a Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université René Descartes, UMR 8601 CNRS, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France
b Faculté des Sciences et des Techniques, Unité de Recherches en Biocatalyse, FRE 2230 CNRS, 2 rue de la Houssinière, BP 92208, 44322 Nantes, France |
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| Abstract: | The synthesis of carbasugars and various aminocyclitols, related to voglibose and acarbose used in the treatment of non-insulino-dependant diabetes, is described from C2-symmetrical bis-epoxides derived from d-mannitol. The methodology involves two key steps: a domino alkylation-cyclization with 2-lithio-1,3-dithiane derivatives, and reduction or reductive amination with a primary amine. These compounds have been evaluated as inhibitors of several glycosidases, and this study indicates notably that the l-ido or d-manno 1-aminocycloheptane-3,4,5,6-tetrol are inhibitors of α-d-glucosidase with Ki in the micromolar range. |
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| Keywords: | aza-disaccharide aminocyclitol bis-epoxide carbasugar cyclization glycosidases reductive amination |
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