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A Diverted Total Synthesis of Mycolactone Analogues: An Insight into Buruli Ulcer Toxins

Authors

  • Anne-Caroline Chany,

    1. Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue A. Werner, 68093 Mulhouse Cedex (France), Fax: (+33) 389-33-68-60
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  • Dr. Virginie Casarotto,

    1. Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue A. Werner, 68093 Mulhouse Cedex (France), Fax: (+33) 389-33-68-60
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  • Dr. Marjorie Schmitt,

    1. Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue A. Werner, 68093 Mulhouse Cedex (France), Fax: (+33) 389-33-68-60
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  • Prof. Dr. Céline Tarnus,

    1. Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue A. Werner, 68093 Mulhouse Cedex (France), Fax: (+33) 389-33-68-60
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  • Dr. Laure Guenin-Macé,

    1. Institut Pasteur, Immunobiologie de l'Infection, 25 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
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  • Dr. Caroline Demangel,

    1. Institut Pasteur, Immunobiologie de l'Infection, 25 rue du Dr. Roux, 75724 Paris Cedex 15 (France)
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  • Dr. Olivier Mirguet,

    1. Lipid Metabolism DPU, GlaxoSmithkline, 25 av. du Québec, 91951 Les Ulis Cedex (France)
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  • Prof. Dr. Jacques Eustache,

    1. Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue A. Werner, 68093 Mulhouse Cedex (France), Fax: (+33) 389-33-68-60
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  • Dr. Nicolas Blanchard

    Corresponding author
    1. Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue A. Werner, 68093 Mulhouse Cedex (France), Fax: (+33) 389-33-68-60
    • Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique EA4566, 3 rue A. Werner, 68093 Mulhouse Cedex (France), Fax: (+33) 389-33-68-60
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Abstract

Mycolactones are complex macrolides responsible for a severe necrotizing skin disease called Buruli ulcer. Deciphering their functional interactions is of fundamental importance for the understanding, and ultimately, the control of this devastating mycobacterial infection. We report herein a diverted total synthesis approach of mycolactones analogues and provide the first insights into their structure–activity relationship based on cytopathic assays on L929 fibroblasts. The lowest concentration inducing a cytopathic effect was determined for selected analogues, allowing a clear picture to emerge by comparison with the natural toxins.

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