Asymmetric Synthesis of a Potent HIV-1 Integrase Inhibitor

J Org Chem. 2016 Nov 4;81(21):10256-10265. doi: 10.1021/acs.joc.6b01229. Epub 2016 Aug 10.

Abstract

The development of a practical asymmetric total synthesis of the potent HIV-1 integrase inhibitor 5 is described. Key transformations include construction of the naphthridine core in a highly efficient manner followed by cyclization of the 8-membered ring. Control of the atropisomers of intermediates and final compound 5 is also described.

MeSH terms

  • Carbon-13 Magnetic Resonance Spectroscopy
  • Cyclization
  • HIV Integrase / drug effects*
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • Naphthyridines / chemistry
  • Proton Magnetic Resonance Spectroscopy

Substances

  • HIV Integrase Inhibitors
  • Naphthyridines
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1