Antineoplastic agents. 278. Isolation and Structure of Axinastatins 2 and 3 from a Western Caroline Island Marine Sponge

George Pettit, Feng Gao, Ronald L. Cerny, Dennis L. Doubek, Larry P. Tackett, Jean M. Schmidt, Jean Chapuis

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

The Republic of Palau marine sponge Axinella sp. was found to be an exceptionally productive source of cell growth inhibitory substances. The strongly antineoplastic polyether macrocyclic lactones halichondrin B (1) and homohalichondrin B (2) were isolated in 1.2 × 10−6% and 5.4 × 10−7% yields, respectively. In addition to axinastatin 1 (3), two new and cytostatic (GI50 values of 0.35 to 0.0072 µg/mL against six human cancer cell lines) cycloheptapeptides designated axinastatins 2 (4) and 3 (5) were discovered in 1.4 × 10−6% and 1.25 × 10−6% yields. Structures were elucidated by high-resolution FABMS and tandem MS/MS techniques augmented by high-field (400 and 500 MHz) 2D-NMR spectral analyses. The absolute configurations were established by a combination of hydrolysis, derivatization, and chiral gas chromatographic methods.

Original languageEnglish (US)
Pages (from-to)1165-1168
Number of pages4
JournalJournal of Medicinal Chemistry
Volume37
Issue number8
DOIs
StatePublished - Apr 1 1994

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Pettit, G., Gao, F., Cerny, R. L., Doubek, D. L., Tackett, L. P., Schmidt, J. M., & Chapuis, J. (1994). Antineoplastic agents. 278. Isolation and Structure of Axinastatins 2 and 3 from a Western Caroline Island Marine Sponge. Journal of Medicinal Chemistry, 37(8), 1165-1168. https://doi.org/10.1021/jm00034a014