An efficient synthesis of an exo-enone analogue of LL-Z1640-2 and evaluation of its protein kinase inhibitory activities

Org Biomol Chem. 2016 Jan 14;14(2):639-645. doi: 10.1039/c5ob01948f.

Abstract

An efficient synthesis of an exo-enone analogue (5) of resorcylic acid lactone (RAL), natural product LL-Z1640-2 (1), has been achieved using a Ni-catalysed regioselective reductive coupling macrocyclisation of an alkyne-aldehyde as a key step. The synthetic route is significantly shorter than those for the natural product and avoids the isomerisation problem of the cis-double bond in the molecule. The preliminary biological evaluation showed that the exo-enone analogue is a potent inhibitor of several important kinases relevant to cancer drug development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Ketones / chemical synthesis
  • Ketones / chemistry
  • Ketones / pharmacology*
  • Lactones / chemical synthesis
  • Lactones / chemistry
  • Lactones / pharmacology*
  • Molecular Structure
  • Phosphotransferases / antagonists & inhibitors*
  • Phosphotransferases / metabolism
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Ketones
  • LL Z1640-2
  • Lactones
  • Protein Kinase Inhibitors
  • Phosphotransferases