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Enantioselective Synthesis of the Complex Rocaglate (−)-Silvestrol

Authors

  • Baudouin Gerard,

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

    1. McGill University, Department of Biochemistry, Room 810, 3655 Drummond St., Montreal, QC, H3G 1Y6, Canada
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  • Jerry Pelletier Prof. Dr.,

    1. McGill University, Department of Biochemistry, Room 810, 3655 Drummond St., Montreal, QC, H3G 1Y6, Canada
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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) 617-358-2847
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  • Financial support from the National Institutes of Health (J.A.P.,Jr., GM-073855) and from the NCI Canada (J.P., 017099), Bristol-Myers Squibb, and Merck Research Laboratories is gratefully acknowledged. We thank Dr. R. Murray Tait for providing natural silvestrol and Dr. Siva Dandapani, Dr. Jean-Charles Marié, Dr. Aaron Beeler, and Mr. Suwei Dong (Boston University) for helpful discussions.

Abstract

original image

The total synthesis of the natural product (−)-silvestrol (1) has been accomplished and features enantioselective [3+2] photocycloaddition of a substituted 3-hydroxyflavone and methyl cinnamate promoted by a chiral Brønsted acid. Initial biological studies indicate a 5–10-fold greater activity of silvestrol as an inhibitor of protein synthesis in HeLa cells than its 1′′′′ diastereomer.

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