Synthesis of the Tetracyclic Cores of the Integrastatins, Epicoccolide A and Epicocconigrone A

J Org Chem. 2019 Sep 20;84(18):11935-11944. doi: 10.1021/acs.joc.9b01796. Epub 2019 Aug 28.

Abstract

The integrastatins, epicoccolide A and epicoccongirone A, are natural products containing a unique [6.6.6.6]-tetracyclic core framework that exhibit a broad spectrum of biological activities. A synthesis of the common core of epicoccolide A and epicocconigrone A has been achieved using an umpolung alkylation-lactonization to assemble an isochromanone from which the bridged 1,3-dioxane was readily assembled. A different strategy was required to access the core on the integrastatins; an initial aryllithium addition to an aldehyde, followed by oxidation and treatment of the masked dihydroxyketone with acid gave the desired core structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Chemistry Techniques, Synthetic / methods*
  • Cyclization
  • Heterocyclic Compounds, Bridged-Ring / chemical synthesis*
  • Heterocyclic Compounds, Bridged-Ring / chemistry
  • Molecular Structure

Substances

  • Heterocyclic Compounds, Bridged-Ring
  • epicoccolide A
  • epicocconigrone A