Maitotoxin: An Inspiration for Synthesis

Authors

  • K. C. Nicolaou,

    Corresponding author
    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA phone: (+1) (0)858 784-2400 fax: (+1) (0)858 784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    • Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA phone: (+1) (0)858 784-2400 fax: (+1) (0)858 784-2469
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  • Robert J. Aversa

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA phone: (+1) (0)858 784-2400 fax: (+1) (0)858 784-2469
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Abstract

Maitotoxin holds a special place in the annals of natural products chemistry as the largest and most toxic secondary metabolite known to date. Its fascinating, ladder-like, polyether molecular structure and diverse spectrum of biological activities elicited keen interest from chemists and biologists, who recognized its uniqueness and potential as a probe and inspiration for research in chemistry and biology. Synthetic studies in the area benefited from methodologies and strategies that were developed as part of chemical synthesis programs directed toward the total synthesis of some of the less complex members of the polyether marine biotoxin class, of which maitotoxin is the flagship. This account focuses on progress made in the authors’ laboratories in the synthesis of large maitotoxin domains with emphasis on methodology development, strategy design, and structural comparisons of the synthesized molecules with the corresponding regions of the natural product. The article concludes with an overview of maitotoxin’s biological profile and future perspectives.

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