From meiogynin A to the synthesis of dual inhibitors of Bcl-xL and Mcl-1 anti-apoptotic proteins

Chem Commun (Camb). 2014 Aug 11;50(62):8593-6. doi: 10.1039/c4cc01830c.

Abstract

The synthesis of one of the most potent dual inhibitors of the anti-apoptotic proteins Bcl-xL and Mcl-1 is reported. This analogue of a natural sesquiterpenoid dimer meiogynin A was elaborated by a convergent asymmetric synthesis with 36% yield in ten steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cycloaddition Reaction / methods*
  • Models, Molecular
  • Molecular Docking Simulation
  • Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / pharmacology
  • bcl-X Protein / antagonists & inhibitors
  • bcl-X Protein / metabolism*

Substances

  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Sesquiterpenes
  • bcl-X Protein
  • meiogynin A