The synthesis and biological evaluation of desepoxyisotedanolide and a comparison with desepoxytedanolide

Angew Chem Int Ed Engl. 2015 Jun 1;54(23):6935-9. doi: 10.1002/anie.201501526. Epub 2015 Apr 27.

Abstract

The tedanolides are biologically active polyketides that exhibit a macrolactone constructed from a primary alcohol. Since polyketidal transformations only generate secondary alcohols, it has been hypothesized by Taylor that this unique lactone could arise from a postketidal transesterification. In order to probe this hypothesis and to investigate the biological profile of the putative precursor of all members of the tedanolide family, we embarked on the synthesis of desepoxyisotedanolide and its biological evaluation in comparison to desepoxytedanolide. The biological experiments unraveled a second target for desepoxytedanolide and provided evidence that the proposed transesterification indeed provides a survival advantage for the producing microorganism.

Keywords: antitumor agents; macrolactones; natural products; polyketides; tedanolide.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Eukaryotic Cells / drug effects
  • Eukaryotic Cells / metabolism
  • Fibroblasts / drug effects
  • Humans
  • Macrolides / chemical synthesis*
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Mice
  • Molecular Conformation
  • Porifera / chemistry
  • Rabbits
  • Structure-Activity Relationship

Substances

  • Macrolides
  • tedanolide