Synthetic Studies toward C-Glucosidic Ellagitannins: A Biomimetic Total Synthesis of 5-O-Desgalloylepipunicacortein A

Authors

  • Dr. Gaëlle Malik,

    1. Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex (France)
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  • Dr. Anna Natangelo,

    1. Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex (France)
    2. Università di Ferrara, Dipartimento di Scienze Farmaceutiche, Via Fossato di Mortara, 17-19, I-44100 Ferrara (Italy)
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  • Prof. Jaime Charris,

    1. Universidad Central de Venezuela, Facultad de Farmacia, Laboratorio de Síntesis Orgánica, Caracas 1051 (Venezuela)
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  • Dr. Laurent Pouységu,

    1. Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex (France)
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  • Prof. Stefano Manfredini,

    1. Università di Ferrara, Dipartimento di Scienze Farmaceutiche, Via Fossato di Mortara, 17-19, I-44100 Ferrara (Italy)
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  • Dr. Dominique Cavagnat,

    1. Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), 351 cours de la Libération, 33405 Talence Cedex (France)
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  • Dr. Thierry Buffeteau,

    1. Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), 351 cours de la Libération, 33405 Talence Cedex (France)
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  • Dr. Denis Deffieux,

    Corresponding author
    1. Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex (France)
    • Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex (France)
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  • Prof. Stéphane Quideau

    Corresponding author
    1. Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex (France)
    • Université de Bordeaux, Institut des Sciences Moléculaires (CNRS-UMR 5255), Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex (France)
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Abstract

C-glucosidic ellagitannins constitute a subclass of bioactive polyphenolic natural products with strong antioxidant properties, as well as promising antitumoral and antiviral activities that are related to their capacity to interact with both functional and structural proteins. To date, most synthetic efforts toward ellagitannins have concerned glucopyranosic species. The development of a synthetic strategy to access C-glucosidic ellagitannins, whose characteristic structural feature includes an atropoisomeric hexahydroxydiphenoyl (HHDP) or a nonahydroxyterphenoyl (NHTP) unit that is linked to an open-chain glucose core by a C-aryl glucosidic bond, is described herein. The total synthesis of the biarylic HHDP-containing 5-O-desgalloylepipunicacortein A (1 β) was achieved by either using the natural ellagic acid bis-lactone as a precursor of the requested HHDP unit or by implementing an atroposelective intramolecular oxidative biarylic coupling to forge this HHDP unit. Both routes converged in the penultimate step of this synthesis to enable a biomimetic formation of the key C-aryl glucosidic bond in the title compound.

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