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⇱ Synthesis of epothilones A and B in solid and solution phase | Nature

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A Corrigendum to this article was published on 06 November 1997

Abstract

Epothilones A and B, two compounds that have been recently isolated1 from myxobacterium Sorangium cellulosum strain 90, have generated intense interest2–16 among chemists, biologists and clinicians owing to the structural complexity, unusual mechanism of interaction with micro tubules and anticancer potential of these molecules. Like taxol* (refs 17, 18), they exhibit cytotoxicity against tumour cells by inducing microtubule assembly and stabilization3,4, even in taxol-resistant cell lines. Following the structural elucidation of these molecules by X-ray crystallography in 19961, several syntheses of epothilones A (refs 12–16) and B (ref. 19) have been reported, indicative of the potential importance of these molecules in the cancer field. Here we report the first solid-phase synthesis of epothilone A, the total synthesis of epothilone B, and the generation of a small epothilone library. The solid-phase synthesis applied here to epothilone A could open up new possibilities in natural-product synthesis and, together with solution-phase synthesis of other epothilones, paves the way for the generation of large combinatorial libraries of these important molecules for biological screening.

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Author information

Authors and Affiliations

  1. Department of Chemsitry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA

    K. C. Nicolaou, N. Winssinger, J. Pastor, S. Ninkovic, F. Sarabia, Y. He, D. Vourloumis & Z. Yang

  2. Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA

    K. C. Nicolaou, N. Winssinger, J. Pastor, S. Ninkovic, F. Sarabia, Y. He, D. Vourloumis & Z. Yang

  3. Medicine Branch, DCS, NCI, National Institutes of Health, Bethesda, Maryland, 20892, USA

    P. Giannakakou

  4. Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, DCTDC, NCI, Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    E. Hamel

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Nicolaou, K., Winssinger, N., Pastor, J. et al. Synthesis of epothilones A and B in solid and solution phase. Nature 387, 268–272 (1997). https://doi.org/10.1038/387268a0

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  • DOI: https://doi.org/10.1038/387268a0

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