The discovery of a novel route to highly substituted α-tropolones enables expedient entry to the core of the gukulenins

Org Lett. 2015 Apr 17;17(8):2030-3. doi: 10.1021/acs.orglett.5b00841. Epub 2015 Apr 3.

Abstract

A simple and general method for the synthesis of highly substituted α-tropolone ethers that allows rapid access to the bis(tropolone) core of the antiproliferative metabolites (-)-gukulenins A and F (3, 4) is described. The reaction proceeds by thermolytic opening of gem-dibromobicyclo[4.1.0]heptane intermediates, which are readily accessed from simple starting materials. Mechanistic studies suggest the reaction proceeds via an autocatalytic process mediated by methyl hypobromite. This synthetic sequence allows access to a broad array of highly substituted α-tropolones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ethers / chemical synthesis
  • Ethers / chemistry
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Molecular Structure
  • Stereoisomerism
  • Terpenes / chemical synthesis*
  • Terpenes / chemistry
  • Tropolone / chemical synthesis*
  • Tropolone / chemistry*

Substances

  • Ethers
  • Heterocyclic Compounds, 4 or More Rings
  • Terpenes
  • gukulenin A
  • Tropolone