Total synthesis, structure revision, and absolute configuration of (-)-brevenal

Haruhiko Fuwa, Makoto Ebine, Andrea J. Bourdelais, Daniel G. Baden, Makoto Sasaki

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Total synthesis of structure 1 originally proposed for brevenal, a nontoxic polycyclic ether natural product isolated from the Florida red tide dinoflagellate, Karenia brevis, was accomplished. The key features of the synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton based on our developed Suzuki-Miyaura coupling chemistry and (ii) stereoselective construction of the multi-substituted (E,E)-dienal side chain by using copper(l) thiophen-2-carboxylate (CuTC)-promoted modified Stille coupling. The disparity of NMR spectra between the synthetic material and the natural product required a revision of the proposed structure. Detailed spectroscopic comparison of synthetic 1 with natural brevenal, coupled with the postulated biosynthetic pathway for marine polyether natural products, suggested that the natural product was most likely represented by 2, the C26 epimer of the proposed structure 1. The revised structure was finally validated by completing the first total synthesis of (-)-2, which also unambiguously established the absolute configuration of the natural product.

Original languageEnglish
Pages (from-to)16989-16999
Number of pages11
JournalJournal of the American Chemical Society
Volume128
Issue number51
DOIs
Publication statusPublished - Dec 27 2006

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Biological Products
Polyethers
Tides
Harmful Algal Bloom
Ethers
Dinoflagellida
Nuclear magnetic resonance
Biosynthetic Pathways
Copper
Skeleton
Ether

All Science Journal Classification (ASJC) codes

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

Cite this

Total synthesis, structure revision, and absolute configuration of (-)-brevenal. / Fuwa, Haruhiko; Ebine, Makoto; Bourdelais, Andrea J.; Baden, Daniel G.; Sasaki, Makoto.

In: Journal of the American Chemical Society, Vol. 128, No. 51, 27.12.2006, p. 16989-16999.

Research output: Contribution to journalArticle

Fuwa, H, Ebine, M, Bourdelais, AJ, Baden, DG & Sasaki, M 2006, 'Total synthesis, structure revision, and absolute configuration of (-)-brevenal', Journal of the American Chemical Society, vol. 128, no. 51, pp. 16989-16999. https://doi.org/10.1021/ja066772y
Fuwa, Haruhiko ; Ebine, Makoto ; Bourdelais, Andrea J. ; Baden, Daniel G. ; Sasaki, Makoto. / Total synthesis, structure revision, and absolute configuration of (-)-brevenal. In: Journal of the American Chemical Society. 2006 ; Vol. 128, No. 51. pp. 16989-16999.
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