Double dearomatization of bis(diphenylphosphinamides) through anionic cyclization. A facile route of accessing multifunctional systems with antitumor properties

J Org Chem. 2007 May 11;72(10):3790-9. doi: 10.1021/jo070276q. Epub 2007 Apr 18.

Abstract

The sequential one-pot double dearomatization of bis(N-benzyl-P,P-diphenylphosphinamides) via anionic cyclization is described for the first time. Protonation and alkylation of the dearomatized dianions provide bis(tetrahydro-2,1-benzazaphospholes) in good yield and with very high regio- and stereocontrol. Acid-catalyzed methanolysis of the bisheterocycles affords bis(methyl gamma-aminophosphinates) stereospecifically. The doubly phosphorylated systems proved to be active against a series of cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / toxicity*
  • Anions / chemistry*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity*
  • Aza Compounds / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclization
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Phosphines / chemistry*
  • Structure-Activity Relationship

Substances

  • Amides
  • Anions
  • Antineoplastic Agents
  • Aza Compounds
  • Phosphines