Synfacts 2008(7): 0667-0667  
DOI: 10.1055/s-2008-1077856
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (+)-Vigulariol

Rezensent(en):Philip Kocienski, Indu Dager
J. Becker, K. Bergander, R. Fröhlich, D. Hoppe*
Westfälische Wilhelms-Universität, Münster, Germany
Asymmetric Total Synthesis and X-Ray Crystal Structure of the Cytotoxic Marine Diterpene (+)-Vigulariol
Angew. Chem. Int. Ed.  2008,  47:  1654-1657  
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Publikationsverlauf

Publikationsdatum:
20. Juni 2008 (online)


Significance

(+)-Vigulariol is a cytotoxic marine diterpene isolated from the sea pen Vigularia juncea and shows cytotoxicity against A549 (human lung adenocarcinoma) cell culture. The key step in the short synthesis involved (1) asymmetric homoaldol reaction of chiral carbamate A with enal B and (2) ring-closing metathesis to form the tricyclic skeleton in H. This type of cyclization was reported unsuccessful earlier.

Comment

A substrate-controlled deprotonation of A and then treatment with aldehyde B gave an inseparable mixture of diastereoisomeric homo­aldol adducts C and D. This mixture was then subjected to a Lewis acid mediated condensation with acetal E to afford tetrahydrofuran G as a major isomer. RCM of G gave the tricylic framework in 45% yield.