The first total synthesis of (+/-)-ingenol

J Am Chem Soc. 2002 Aug 21;124(33):9726-8. doi: 10.1021/ja026600a.


The first total synthesis of (+/-)-ingenol has been achieved. The key features of the synthesis include the use of a highly diastereoselective Michael reaction to fix the C-11 methyl stereochemistry and the incorporation of the dimethylcyclopropane via diastereoselective carbene addition to the Delta13,14 olefin. The intramolecular dioxenone photoaddition-fragmentation sequence leads to the establishment of the critical C-8/C-10 trans intrabridgehead stereochemistry, a central challenge in the synthesis of ingenanes. The completion of the synthesis proceeds using the C-6alpha hydroxymethyl group as the sole handle for oxidation of seven contiguous carbon centers.

Publication types

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

MeSH terms

  • Diterpenes / chemical synthesis*
  • Diterpenes / chemistry
  • Molecular Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Stereoisomerism


  • Diterpenes
  • ingenol