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Synthesis and Biological Evaluation of ABCD Ring Fragments of the Kibdelones

Authors

  • David L. Sloman,

    1. Department of Chemistry, Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, MA 02215 (USA), Fax: (+1) 617-358-2847
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  • Branko Mitasev,

    1. Department of Chemistry, Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, MA 02215 (USA), Fax: (+1) 617-358-2847
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  • Stephen S. Scully,

    1. Department of Chemistry, Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, MA 02215 (USA), Fax: (+1) 617-358-2847
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  • Dr. John A. Beutler,

    1. Molecular Targets Laboratory, NCI, Frederick, MD 21702 (USA)
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  • Prof. John A. Porco Jr.

    Corresponding author
    1. Department of Chemistry, Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, MA 02215 (USA), Fax: (+1) 617-358-2847
    • Department of Chemistry, Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, MA 02215 (USA), Fax: (+1) 617-358-2847
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  • Financial support from the National Institutes of Health (R01 CA137270) and Merck Research Laboratories is gratefully acknowledged. We thank Andrew Little and Dr. Stéphane Roche for extremely helpful and stimulating discussions, and Drs. Richard Ball and Jeff Bacon for X-ray crystallographic data.

Abstract

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Arylation goes platinum: The synthesis of the ABCD ring fragments of the kibdelones has been achieved through a novel PtIV-catalyzed arylation of a quinone monoketal followed by photocyclization (see scheme). Biological evaluation in the NCI 60-cell screen revealed that the kibdelone ABCD ring analogues were about 2000 times less active than kibdelones B and C, suggesting that the tetrahydroxanthone structure of the kibdelones is crucial for cytotoxicity.

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