Fructose-1,6-Bisphosphate Aldolase-Mediated Synthesis of Aminocyclitols (Analogues of Valiolamine) and their Evaluation as Glycosidase Inhibitors

Authors

  • Lahssen El Blidi Dr.,

    1. Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, 24 av des Landais, F-63177 Aubière cedex (France), Fax: (+33) 4-73-40-77-17
    2. CNRS, UMR 6504, 24 av des Landais, F-63177 Aubière cedex (France)
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  • Zeinab Assaf,

    1. Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, 24 av des Landais, F-63177 Aubière cedex (France), Fax: (+33) 4-73-40-77-17
    2. CNRS, UMR 6504, 24 av des Landais, F-63177 Aubière cedex (France)
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  • Flora Camps Bres,

    1. Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, 24 av des Landais, F-63177 Aubière cedex (France), Fax: (+33) 4-73-40-77-17
    2. CNRS, UMR 6504, 24 av des Landais, F-63177 Aubière cedex (France)
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  • Henri Veschambre Dr.,

    1. Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, 24 av des Landais, F-63177 Aubière cedex (France), Fax: (+33) 4-73-40-77-17
    2. CNRS, UMR 6504, 24 av des Landais, F-63177 Aubière cedex (France)
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  • Vincent Théry Dr.,

    1. Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, 24 av des Landais, F-63177 Aubière cedex (France), Fax: (+33) 4-73-40-77-17
    2. CNRS, UMR 6504, 24 av des Landais, F-63177 Aubière cedex (France)
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  • Jean Bolte Prof.,

    1. Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, 24 av des Landais, F-63177 Aubière cedex (France), Fax: (+33) 4-73-40-77-17
    2. CNRS, UMR 6504, 24 av des Landais, F-63177 Aubière cedex (France)
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  • Marielle Lemaire Prof.

    1. Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, 24 av des Landais, F-63177 Aubière cedex (France), Fax: (+33) 4-73-40-77-17
    2. CNRS, UMR 6504, 24 av des Landais, F-63177 Aubière cedex (France)
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Abstract

A highly stereoselective method for the preparation of nitro- and aminocyclitols, using fructose-1,6-bisphosphate aldolase, which catalyzes the aldol reaction of dihydroxyacetone phosphate (DHAP) on hydroxynitrobutanals, is reported. The key part of the synthesis is based on a one-pot /two-enzyme process whereby three reactions take place; rabbit muscle aldolase (RAMA) catalyzed aldolization, phytase-catalyzed phosphate hydrolysis, and intramolecular spontaneous nitroaldolization. Two families of nitrocyclitols were obtained depending on the carbon configuration in the β position to the nitro group. Reduction of the latter afforded the aminocyclitols. Evaluation of the inhibition properties of the amines towards five commercially available glycosidases has shown selectivity for β-glucosidase and β-galactosidase.

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