Total Synthesis of the Unusual Marine Alkaloid (—)-Papuamine Utilizing a Novel Imino Ene Reaction

Robert M. Borzilleri, Steven M. Weinreb, Masood Parvez

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

A concise enantioselective total synthesis of the recently isolated antibacterial and antifungal marine alkaloid (—)-papuamine (1) is described. The key feature of the synthesis includes the development and subsequent implementation of a novel pericyclic imino ene reaction. Starting from readily available enantiomerically pure acid ester 11, allenyl silane N-benzyl imines 24 and 27 were generated in situ from aldehydes 23a/b. These imines undergo concerted stereospecific imino ene reactions to afford silyl acetylenes 25 and 28, respectively, in high yields. The ene reactions were found to be promoted both thermally in refluxing toluene and at lower temperatures using the Lewis acid stannic chloride as a catalyst. Desilylation of compounds 25 and 28 afforded terminal alkynes 26 and 29, respectively, whose structures and stereochemistry were unambiguously established by single crystal X-ray structure analysis of the corresponding HC1 salts. In a more highly convergent approach to the alkaloid 1, aldehyde allenyl silane 23a was treated with 0.5 equiv of 1,3-diaminopropane in refluxing toluene to afford homopropargylic diamine 40 as one stereoisomer via a double imino ene reaction, which effectively established the remaining four of the eight stereogenic centers of papuamine in one simple operation. To complete the route to the natural enantiomer of papuamine, a Pd(II) catalyzed macrocyclization of bis-E-vinyl stannane 42b was effected in moderate yield.

Original languageEnglish (US)
Pages (from-to)10905-10913
Number of pages9
JournalJournal of the American Chemical Society
Volume117
Issue number44
DOIs
StatePublished - Jan 1 1995

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Alkaloids
Aldehydes
Silanes
Toluene
Imines
Alkynes
Stereochemistry
Acids
Enantiomers
Acetylene
Lewis Acids
Esters
Stereoisomerism
Diamines
Single crystals
Salts
X rays
Catalysts
X-Rays
Temperature

All Science Journal Classification (ASJC) codes

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

Cite this

Borzilleri, Robert M. ; Weinreb, Steven M. ; Parvez, Masood. / Total Synthesis of the Unusual Marine Alkaloid (—)-Papuamine Utilizing a Novel Imino Ene Reaction. In: Journal of the American Chemical Society. 1995 ; Vol. 117, No. 44. pp. 10905-10913.
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Total Synthesis of the Unusual Marine Alkaloid (—)-Papuamine Utilizing a Novel Imino Ene Reaction. / Borzilleri, Robert M.; Weinreb, Steven M.; Parvez, Masood.

In: Journal of the American Chemical Society, Vol. 117, No. 44, 01.01.1995, p. 10905-10913.

Research output: Contribution to journalArticle

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