Modular Total Synthesis of Protein Kinase C Activator (-)-Indolactam V

Org Lett. 2016 May 6;18(9):2008-11. doi: 10.1021/acs.orglett.6b00614. Epub 2016 Apr 13.

Abstract

A concise, eight-step total synthesis of (-)-indolactam V, a nanomolar agonist of protein kinase C, is reported. The synthesis relies upon an efficient copper-catalyzed amino acid arylation to establish the indole C4-nitrogen bond. This cross-coupling method is applicable to a range of hydrophobic amino acids, providing a platform for further diversification of indolactam alkaloid scaffolds and studies on their potent biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Lactams / pharmacology
  • Molecular Structure
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Stereoisomerism

Substances

  • Indoles
  • Lactams
  • Protein Kinase Inhibitors
  • indolactam V
  • Protein Kinase C