Synthesis and biological evaluation of potent glycosidase inhibitors: 4-deoxy-4,4-difluoroisofagomine and analogues |
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| Authors: | Rui-jie Li Cyril Rousseau Ruo-wen Wang |
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| Institution: | a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, China
b Department of Chemistry, University of Copenhagen, Universitetsparken 5, Denmark |
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| Abstract: | A series of 4,4-difluoroisofagomine analogues were synthesized. These compounds were tested for inhibition of eight glycosidases. The 3R,5R isomer 1 is a new and potent inhibitor against β-glucosidase from almonds with Ki value of 1.2 μM. The influence of the gem-difluoromethylene group (CF2) on binding to glycosidases is discussed. It is concluded that only non-essential hydroxyl groups can be replaced by the gem-difluoro group and that in such a case (β-glycosidase) the change in inhibition is, interestingly, a result of the change in base strength. |
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| Keywords: | Iminosugar Glycosidases inhibitors Fluorinated compounds |
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