Total synthesis of (-)-heptemerone B and (-)-guanacastepene E

Aubry K. Miller, Chambers C. Hughes, Joshua J. Kennedy-Smith, Stefan N. Gradl, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

A concise, stereoselective, and convergent total synthesis of the unnatural enantiomer of the neodolastane diterpenoid heptemerone B has been completed. Saponification of (-)-heptemerone afforded (-)-guanacastepene E. The absolute stereochemistry of (-)-heptemerone B was thus established as 5-(S), the same as (-)-guanacastepene E. The longest linear sequence of the synthesis comprises 17 (18) steps from simple known starting materials. Our general synthetic approach integrates a diverse set of reactions, including an intramolecular Heck reaction to create one quaternary stereocenter and a cuprate conjugate addition for the establishment of the other. The central seven-membered ring was closed with an uncommon electrochemical oxidation, whereas the five-membered ring was formed through ring-closing metathesis. The absolute configuration of the two key building blocks was established through an asymmetric reduction and an asymmetric ene reaction.

Original languageEnglish (US)
Pages (from-to)17057-17062
Number of pages6
JournalJournal of the American Chemical Society
Volume128
Issue number51
DOIs
StatePublished - Dec 27 2006

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Saponification
Stereochemistry
Enantiomers
Diterpenes
Electrochemical oxidation
heptemerone B
guanacastepene E
ent-7beta,14-dihydroxy-11alpha-methoxy-18-aldehyde-11beta-20-epoxy-kaur-16-en-15-one

ASJC Scopus subject areas

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

Cite this

Miller, A. K., Hughes, C. C., Kennedy-Smith, J. J., Gradl, S. N., & Trauner, D. (2006). Total synthesis of (-)-heptemerone B and (-)-guanacastepene E. Journal of the American Chemical Society, 128(51), 17057-17062. https://doi.org/10.1021/ja0660507

Total synthesis of (-)-heptemerone B and (-)-guanacastepene E. / Miller, Aubry K.; Hughes, Chambers C.; Kennedy-Smith, Joshua J.; Gradl, Stefan N.; Trauner, Dirk.

In: Journal of the American Chemical Society, Vol. 128, No. 51, 27.12.2006, p. 17057-17062.

Research output: Contribution to journalArticle

Miller, AK, Hughes, CC, Kennedy-Smith, JJ, Gradl, SN & Trauner, D 2006, 'Total synthesis of (-)-heptemerone B and (-)-guanacastepene E', Journal of the American Chemical Society, vol. 128, no. 51, pp. 17057-17062. https://doi.org/10.1021/ja0660507
Miller AK, Hughes CC, Kennedy-Smith JJ, Gradl SN, Trauner D. Total synthesis of (-)-heptemerone B and (-)-guanacastepene E. Journal of the American Chemical Society. 2006 Dec 27;128(51):17057-17062. https://doi.org/10.1021/ja0660507
Miller, Aubry K. ; Hughes, Chambers C. ; Kennedy-Smith, Joshua J. ; Gradl, Stefan N. ; Trauner, Dirk. / Total synthesis of (-)-heptemerone B and (-)-guanacastepene E. In: Journal of the American Chemical Society. 2006 ; Vol. 128, No. 51. pp. 17057-17062.
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