Lyngbyastatin 1 and Ibu-epilyngbyastatin 1: Synthesis, stereochemistry, and NMR line broadening

Ruoli Bai, Robert B. Bates, Ernest Hamel, Richard E. Moore, Pichaya Nakkiew, George Pettit, Bilal A. Sufi

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The synthesis of a lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture combined with NMR and molecular modeling studies proved that natural lyngbyastatin 1 was only one Ibu epimer rather than a mixture of both and that the configuration of this epimer in the Ibu unit was R. The substance isolated with lyngbyastatin 1 was Ibu-epidolastatin 12. The extreme broadness in the proton NMR spectra of lyngbyastatin 1 and Ibu-epidolastatin 12 was exchange broadening due to rotation about the Ibu-Ala amide bond. It was a consequence of (1) a small energy difference between the cis and trans forms of this bond, (2) a substantial difference in conformation between these forms, and (3) a lowered barrier between them compared to most amide bonds (due to steric hindrance). The synthetic lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture had significant activities against cancer cells and in stimulating actin polymerization, but was less active than dolastatin 11 in all assays.

Original languageEnglish (US)
Pages (from-to)1824-1829
Number of pages6
JournalJournal of Natural Products
Volume65
Issue number12
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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    Bai, R., Bates, R. B., Hamel, E., Moore, R. E., Nakkiew, P., Pettit, G., & Sufi, B. A. (2002). Lyngbyastatin 1 and Ibu-epilyngbyastatin 1: Synthesis, stereochemistry, and NMR line broadening. Journal of Natural Products, 65(12), 1824-1829. https://doi.org/10.1021/np020117w