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

J Am Chem Soc. 2006 Dec 27;128(51):17057-62. doi: 10.1021/ja0660507.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cyclization
  • Diterpenes / chemical synthesis*
  • Diterpenes / chemistry
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Stereoisomerism


  • Diterpenes
  • guanacastepene
  • heptemerone B