The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15

George Pettit, Timothy J. Thornton, Jeffrey T. Mullaney, Michael R. Boyd, Delbert L. Herald, Sheo Bux Singh, Erik J. Flahive

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c → 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.

Original languageEnglish (US)
Pages (from-to)12097-12108
Number of pages12
JournalTetrahedron
Volume50
Issue number42
DOIs
StatePublished - 1994

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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    Pettit, G., Thornton, T. J., Mullaney, J. T., Boyd, M. R., Herald, D. L., Singh, S. B., & Flahive, E. J. (1994). The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15. Tetrahedron, 50(42), 12097-12108. https://doi.org/10.1016/S0040-4020(01)89562-4