Dearomatizing anionic cyclization of phosphonamides. A route to phosphonic acid derivatives with antitumor properties

Org Lett. 2008 Sep 18;10(18):3981-4. doi: 10.1021/ol801463g. Epub 2008 Aug 20.

Abstract

Deprotonation of bis(N-benzyl-N-methyl)-P-arylphosphonic diamides with s-BuLi in THF at -90 degrees C takes place selectively at the benzylic position. The anions undergo intramolecular attack to the P-aryl ring leading to dearomatized species that were trapped with a series of electrophiles (MeOH, ArOH, BnBr, aliphatic and aromatic aldehydes, and benzophenone) in very high yield, and with high regio- and stereocontrol. The dearomatized products were smoothly transformed into gamma-aminophosphonic acids under acidic conditions. Preliminary screening for antitumor activity showed promising levels of activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclization
  • Humans
  • Lithium / chemistry
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry*
  • Organophosphonates / pharmacology*

Substances

  • Amides
  • Antineoplastic Agents
  • Organophosphonates
  • Lithium