Synthesis of (±)-actinophyllic acid and analogs: Applications of cascade reactions and diverted total synthesis

Brett A. Granger, Ivan T. Jewett, Jeffrey D. Butler, Bruce Hua, Claire E. Knezevic, Elizabeth I. Parkinson, Paul J. Hergenrother, Stephen F. Martin

Research output: Contribution to journalArticle

Abstract

Actinophyllic acid is a biologically active indole alkaloid with a unique structural framework that incorporates five contiguous stereocenters. A total synthesis of (±)-actinophyllic acid has been completed that proceeds in only 10 steps from readily available, known compounds and with the isolation of nine intermediates. The synthesis features a novel cascade of reactions of N-stabilized carbocations with π-nucleophiles to create the tetracyclic core of actinophyllic acid in a single chemical operation. This pivotal cascade sequence generates substructures of the actinophyllic acid core that are not otherwise accessible, and one key intermediate was modified to furnish several novel compounds having potentially promising anticancer activity, one of which induces cell death in a wide range of cancer cell lines.

Original languageEnglish (US)
Pages (from-to)12984-12986
Number of pages3
JournalJournal of the American Chemical Society
Volume135
Issue number35
DOIs
StatePublished - Sep 4 2013

Fingerprint

Acids
acid
Chemical operations
Indole Alkaloids
Alkaloids
Nucleophiles
alkaloid
Cell death
cancer
Cell Death
Cells
Cell Line
actinophyllic acid
Neoplasms
chemical

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Granger, B. A., Jewett, I. T., Butler, J. D., Hua, B., Knezevic, C. E., Parkinson, E. I., ... Martin, S. F. (2013). Synthesis of (±)-actinophyllic acid and analogs: Applications of cascade reactions and diverted total synthesis. Journal of the American Chemical Society, 135(35), 12984-12986. https://doi.org/10.1021/ja4070206

Synthesis of (±)-actinophyllic acid and analogs : Applications of cascade reactions and diverted total synthesis. / Granger, Brett A.; Jewett, Ivan T.; Butler, Jeffrey D.; Hua, Bruce; Knezevic, Claire E.; Parkinson, Elizabeth I.; Hergenrother, Paul J.; Martin, Stephen F.

In: Journal of the American Chemical Society, Vol. 135, No. 35, 04.09.2013, p. 12984-12986.

Research output: Contribution to journalArticle

Granger, Brett A. ; Jewett, Ivan T. ; Butler, Jeffrey D. ; Hua, Bruce ; Knezevic, Claire E. ; Parkinson, Elizabeth I. ; Hergenrother, Paul J. ; Martin, Stephen F. / Synthesis of (±)-actinophyllic acid and analogs : Applications of cascade reactions and diverted total synthesis. In: Journal of the American Chemical Society. 2013 ; Vol. 135, No. 35. pp. 12984-12986.
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