Bufadienolides. 7. Synthesis of 3β-acetoxy-5α,14α-bufa-20,22-dienolide

George Pettit, Dyral C. Fessler, Kenneth D. Paull, Peter Hofer, John C. Knight

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

A new synthetic route to 5-substituted 2-pyrones is described. Alkylation of enamine 1 with methyl acrylate, cyclization of carboxylic acid 2b employing p-toluenesulfonic acid in benzene, and dehydrogenation of enol lactone 3 with a palladium catalyst or by a N-bromosuccinimide sequence comprised the key steps to α-pyrone 5. Other methods (utilizing derivatives of acetic acid) investigated for the enol lactonization reaction gave mainly lactone 4. Application to bufadienolide chemistry was studied by transformation of dehydroepiandrosterone via intermediates 6-8 to 3β-acetoxy-14α-bufa-5,20(21)-dienolide (9). Similar conversion of epiandrosterone acetate (10) led to bufenolide 16, which was dehydrogenated to bufadienolide 17 using sulfur. Other dehydrogenation methods, including those quite useful with enol lactone 3, were unsatisfactory.

Original languageEnglish (US)
Pages (from-to)1398-1404
Number of pages7
JournalJournal of Organic Chemistry
Volume35
Issue number5
StatePublished - 1970

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Bufanolides
Lactones
Dehydrogenation
Bromosuccinimide
Androsterone
Pyrones
Dehydroepiandrosterone
Cyclization
Alkylation
Palladium
Carboxylic Acids
Benzene
Sulfur
Acetic Acid
Acetates
Derivatives
Catalysts
bufadienolide

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Pettit, G., Fessler, D. C., Paull, K. D., Hofer, P., & Knight, J. C. (1970). Bufadienolides. 7. Synthesis of 3β-acetoxy-5α,14α-bufa-20,22-dienolide. Journal of Organic Chemistry, 35(5), 1398-1404.

Bufadienolides. 7. Synthesis of 3β-acetoxy-5α,14α-bufa-20,22-dienolide. / Pettit, George; Fessler, Dyral C.; Paull, Kenneth D.; Hofer, Peter; Knight, John C.

In: Journal of Organic Chemistry, Vol. 35, No. 5, 1970, p. 1398-1404.

Research output: Contribution to journalArticle

Pettit, G, Fessler, DC, Paull, KD, Hofer, P & Knight, JC 1970, 'Bufadienolides. 7. Synthesis of 3β-acetoxy-5α,14α-bufa-20,22-dienolide', Journal of Organic Chemistry, vol. 35, no. 5, pp. 1398-1404.
Pettit, George ; Fessler, Dyral C. ; Paull, Kenneth D. ; Hofer, Peter ; Knight, John C. / Bufadienolides. 7. Synthesis of 3β-acetoxy-5α,14α-bufa-20,22-dienolide. In: Journal of Organic Chemistry. 1970 ; Vol. 35, No. 5. pp. 1398-1404.
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