An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine containing SRC SH2 ligand

Bioorg Med Chem Lett. 1999 Nov 1;9(21):3109-12. doi: 10.1016/s0960-894x(99)00545-4.

Abstract

A CuBr-mediated, regioselective cross-coupling between methyl 2,5-diiodobenzoate (4) and [(diethoxyphosphinyl)difluoromethyl]zinc bromide is reported. Palladium-catalyzed incorporation of an amino acid side chain, followed by subsequent modifications resulted in the rapid construction of 2. Compound 2 was designed to engage Cys188 of the Src SH2 domain, however, this was not observed spectroscopically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cysteine / chemistry
  • Fluorine Compounds / chemical synthesis*
  • Fluorine Compounds / pharmacology
  • Ligands
  • Molecular Structure
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / pharmacology
  • Phenylalanine / analogs & derivatives*
  • Protein Binding
  • Protein-Tyrosine Kinases / chemistry
  • src Homology Domains*

Substances

  • Fluorine Compounds
  • Ligands
  • Organophosphonates
  • Phenylalanine
  • Protein-Tyrosine Kinases
  • Cysteine