Determination of the absolute configuration of phosphinic analogues of glutamate

Org Biomol Chem. 2015 Jan 28;13(4):1106-12. doi: 10.1039/c4ob01960a. Epub 2014 Nov 24.


A series of phosphinic glutamate derivatives (e.g.LSP1-2111) have been proven to be potent agonists of metabotropic glutamate (mGlu) receptors and shown promising in vivo activity. However, so far all were synthesized and tested as a mixture of two diastereomers whose absolute and relative configurations are not known. In this study, the stereomers were separated on a Crownpack CR(+) column and their absolute configuration was assessed by means of a diastereoselective synthesis. Both separated L-stereomers activated the mGlu4 receptor with EC50's of 0.72 and 4.4 μM for (1S,1'S)-and (1S,1'R)-LSP1-2111, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glutamic Acid / chemistry*
  • Glutamic Acid / pharmacology
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Organophosphorus Compounds / chemistry*
  • Receptors, Metabotropic Glutamate / agonists


  • Organophosphorus Compounds
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid