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Synfacts 2006(10): 0987-0987  
DOI: 10.1055/s-2006-949330
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (±)-Haouamine A

Contributor(s):Philip Kocienski, Thomas Snaddon
P. S. Baran*, N. Z. Burns
The Scripps Research Institute, La Jolla, USA
Total Synthesis of (±)-Haouamine A
J. Am. Chem. Soc.  2006,  128:  3908-3909  
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Publication History

Publication Date:
21 September 2006 (online)

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Key words

aziridinium ion - Stille reaction - Diels-Alder reaction

Significance

Isolated from the tunicate Aplidium haouarianum, haouamine A exhibits selective activity against human colon cancer. Haouamine A exists as an inseparable mixture of isomers due to inversion of the nitrogen in the tetrahydropyridine ring. In addition, the highly strained paracyclophane moiety contains a bent aromatic ring.

Comment

Treatment of oxime A with electrophilic bromine source B gave nitrone C after 5-exo-trig cyclization. Reduction of C followed by heating induced ring expansion via aziridinium ion E. Prolonged microwave heating of H induced a pyrone-alkyne Diels-Alder reaction with concomitant loss of CO2. Subsequent deacetylation gave haou­amine A. For an alternative approach based on a 1,3-dipolar cycloaddition strategy, see: J. H. Jeong, S. M. Weinreb Org. Lett. 2006, 8, 2309-2312.

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