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 Citations (Scopus)

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

Fingerprint

Stereochemistry
stereochemistry
Nuclear magnetic resonance
amides
synthesis
Amides
polymerization
protons
actin
Molecular modeling
Polymerization
energy
assays
Conformations
Protons
Actins
Assays
Cells
Ibu-epilyngbyastatin 1
lyngbyastatin 1

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Lyngbyastatin 1 and Ibu-epilyngbyastatin 1 : Synthesis, stereochemistry, and NMR line broadening. / Bai, Ruoli; Bates, Robert B.; Hamel, Ernest; Moore, Richard E.; Nakkiew, Pichaya; Pettit, George; Sufi, Bilal A.

In: Journal of Natural Products, Vol. 65, No. 12, 01.12.2002, p. 1824-1829.

Research output: Contribution to journalArticle

Bai, Ruoli ; Bates, Robert B. ; Hamel, Ernest ; Moore, Richard E. ; Nakkiew, Pichaya ; Pettit, George ; Sufi, Bilal A. / Lyngbyastatin 1 and Ibu-epilyngbyastatin 1 : Synthesis, stereochemistry, and NMR line broadening. In: Journal of Natural Products. 2002 ; Vol. 65, No. 12. pp. 1824-1829.
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AU - Pettit, George

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