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Published on: July 10, 2018
Determination of the absolute configuration of phosphinic analogues of glutamate
Bruno Commare1, Delphine Rigault, Isabelle A Lemasson
1Laboratoire de Chimie & Biochimie Pharmacologiques et Toxicologiques, UMR CNRS 8601, Université Paris Descartes, Sorbonne Paris Cité, 45, rue des Saints-Pères 75270, Paris cedex 06, France. francine.acher@parisdescartes.fr.
Abstract:
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.
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