Communication

Synthesis and Conformational Analysis of (E)-9,10-Dehydroepothilone B: A Suggestive Link between the Chemistry and Biology of Epothilones†

  1. Fumihiko Yoshimura Dr.1,2,
  2. Alexey Rivkin Dr.1,2,
  3. Ana E. Gabarda Dr.1,2,
  4. Ting-Chao Chou Dr.3,
  5. Huajin Dong Dr.3,
  6. George Sukenick Dr.4,
  7. Florence F. Morel5,
  8. Richard E. Taylor Prof.5,
  9. Samuel J. Danishefsky Prof.1,2

Article first published online: 5 JUN 2003

DOI: 10.1002/anie.200351407

Issue

Angewandte Chemie International Edition

Angewandte Chemie International Edition

Volume 42, Issue 22, pages 2518–2521, June 6, 2003

Additional Information

How to Cite

Yoshimura, F., Rivkin, A., Gabarda, A. E., Chou, T.-C., Dong, H., Sukenick, G., Morel, F. F., Taylor, R. E. and Danishefsky, S. J. (2003), Synthesis and Conformational Analysis of (E)-9,10-Dehydroepothilone B: A Suggestive Link between the Chemistry and Biology of Epothilones. Angew. Chem. Int. Ed., 42: 2518–2521. doi: 10.1002/anie.200351407

Author Information

  1. 1

    Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021, USA, Fax: (+1) 212-772-8691

  2. 2

    Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, NY 10027, USA

  3. 3

    Preclinical Pharmacology Core Facility, Sloan-Kettering Institute for Cancer Research

  4. 4

    NMR Analytical Core Facility, Sloan-Kettering Institute for Cancer Research

  5. 5

    Department of Chemistry and Biochemistry, Walther Cancer Research Center, University of Notre Dame, Notre Dame, IN 46556-5670, USA

  1. †

    This work was supported by the National Institutes of Health (CA-28824). F.Y. is a Uehara Memorial Foundation Fellow. A.R. is a NIH Cancer Pharmacology Fellow (T32-CA62948). A.E.G. is a MSKCC Experimental Therapeutics Center Fellow. We thank Ms. Sylvi Rusli (NMR Core Facility, CA-02848) and Mrs. Anna Dudkina for mass spectral analyses.

Publication History

  1. Issue published online: 5 JUN 2003
  2. Article first published online: 5 JUN 2003
  3. Manuscript Received: 14 MAR 2003

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Keywords:

  • antitumor agents;
  • conformational analysis;
  • natural products;
  • structure–activity relationships
Thumbnail image of graphical abstract

The most potent epothilone analogue reported to date was obtained by incorporation of an E double bond at C9[BOND]C10 in the epothilone B series (see picture). Molecular modeling, NMR spectroscopic analysis, and chemical observations were used to rationalize the remarkable potency-enhancing effect of the double bond.

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