Formal synthesis of berkelic acid: a lesson in α-alkylation chemistry

J Org Chem. 2012 Jan 6;77(1):400-16. doi: 10.1021/jo201988m. Epub 2011 Nov 28.


The full details of our enantioselective formal synthesis of the biologically active natural product berkelic acid are described. The insertion of the C-18 methyl group proved challenging, with three different approaches investigated to install the correct stereochemistry. Our initial Horner-Wadsworth-Emmons/oxa-Michael approach to the berkelic acid core proved unsuccessful upon translation to the natural product itself. However, addition of a silyl enol ether to an oxonium ion, followed by a one-pot debenzylation/spiroketalisation/thermodynamic equilibration procedure, afforded the tetracyclic structure of the berkelic acid core as a single diastereoisomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Catalysis
  • Copper / chemistry
  • Molecular Structure
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Stereoisomerism
  • Thermodynamics


  • Spiro Compounds
  • berkelic acid
  • Copper