The Cephalostatins. 22. Synthesis of bis-steroidal pyrazine pyrones

George Pettit, Bryan R. Moser, Ricardo F. Mendonça, John C. Knight, Fiona Hogan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cephalostatin 1 (1), a remarkably strong cancer cell growth inhibitory trisdecacyclic, bis-steroidal pyrazine isolated from the marine tube worm Cephalodiscus gilchristi, continues to be an important target for practical total syntheses and a model for the discovery of less complex structural modifications with promising antineoplastic activity. In the present study, the cephalostatin E and F rings were greatly simplified by replacement at C-17 with an α-pyrone (in 12), typical of the steroidal bufodienolides, and by a dihydro-γ- pyrone (in 16). The synthesis of pyrazine 12 from 5α- dihydrotestosterone (nine steps, 8% overall yield) provided the first route to a bis-bufadienolide pyrazine. Dihydro-γ-pyrone 16 was synthesized in eight steps from ketone 13. While only insignificant cancer cell growth inhibitory activity was found for pyrones 12 and 16, the results provided further support for the necessity of more closely approximating the natural D-F ring system of cephalostatin 1 in order to obtain potent antineoplastic activity.

Original languageEnglish (US)
Pages (from-to)1063-1069
Number of pages7
JournalJournal of Natural Products
Volume75
Issue number6
DOIs
StatePublished - Jun 22 2012

Fingerprint

Pyrones
Pyrazines
Cell growth
Antineoplastic Agents
Dihydrotestosterone
Growth
Ketones
Neoplasms
cephalostatin I

ASJC Scopus subject areas

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

Cite this

The Cephalostatins. 22. Synthesis of bis-steroidal pyrazine pyrones. / Pettit, George; Moser, Bryan R.; Mendonça, Ricardo F.; Knight, John C.; Hogan, Fiona.

In: Journal of Natural Products, Vol. 75, No. 6, 22.06.2012, p. 1063-1069.

Research output: Contribution to journalArticle

Pettit, G, Moser, BR, Mendonça, RF, Knight, JC & Hogan, F 2012, 'The Cephalostatins. 22. Synthesis of bis-steroidal pyrazine pyrones', Journal of Natural Products, vol. 75, no. 6, pp. 1063-1069. https://doi.org/10.1021/np300069z
Pettit, George ; Moser, Bryan R. ; Mendonça, Ricardo F. ; Knight, John C. ; Hogan, Fiona. / The Cephalostatins. 22. Synthesis of bis-steroidal pyrazine pyrones. In: Journal of Natural Products. 2012 ; Vol. 75, No. 6. pp. 1063-1069.
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