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Synthesis of Azaphilones and Related Molecules by Employing Cycloisomerization of o-Alkynylbenzaldehydes

Authors

  • Jianglong Zhu,

    1. Department of Chemistry, Center for Chemical Methodology and Library Development, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA, Fax: (+1) 617-353-6466
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  • Andrew R. Germain,

    1. Department of Chemistry, Center for Chemical Methodology and Library Development, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA, Fax: (+1) 617-353-6466
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  • John A. Porco Jr. Prof. Dr.

    1. Department of Chemistry, Center for Chemical Methodology and Library Development, Boston University, 590 Commonwealth Avenue, Boston, MA 02215, USA, Fax: (+1) 617-353-6466
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  • We thank Dr. Takafumi Kohama (Sankyo Co. LTD.) for providing 1H and 13C NMR spectra of S-15183a and Dr. Emil Lobkovsky (Cornell University) for X-ray crystal structure analysis. We thank CEM Corporation (Matthews, NC) for providing the Explorer microwave system, Bristol-Myers Squibb for an unrestricted Grant in Synthetic Organic Chemistry (J.A.P, Jr.), and Novartis Pharma AG for research support.

Abstract

original image

Right to the core: Gold(III)-catalyzed cycloisomerization of o-alkynylbenzaldehydes to 2-benzopyrylium salts and subsequent in situ oxidation have been employed to prepare the core structure of azaphilone natural products, such as the sphingosine kinase inhibitor S-15183 (see scheme, DCE=1,2-dichloroethane, TFA=trifluoroacetic acid)), and several unnatural azaphilones.

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