Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid

  • J Med Chem. 2008 Apr 10;51(7):2311-5. doi: 10.1021/jm701394a.
Andrea Pinto  1 ,  Paola Conti ,  Marco De Amici ,  Lucia Tamborini ,  Ulf Madsen ,  Birgitte Nielsen ,  Thomas Christesen ,  Hans Bräuner-Osborne ,  Carlo De Micheli
Affiliations
  • 1. Istituto di Chimica Farmaceutica e Tossicologica P. Pratesi, Università degli Studi di Milano, Via Mangiagalli 25, Milan, Italy.
PMID: 18338843 DOI: 10.1021/jm701394a
Abstract

The two enantiomeric pairs of erythro- and threo-amino-(3'-hydroxy-4',5'-dihydro-isoxazol-5'-yl)-acetic acids were synthesized via the 1,3-dipolar cycloaddition of bromonitrile oxide to ( R)- or ( S)-3-( tert-butoxycarbonyl)-2,2-dimethyl-4-vinyloxazolidine. The pharmacological profiles of the studied Amino acids reflect the relationship between the activity/selectivity and the stereochemistry of the two stereogenic centers: while the (2 S,5' S) stereoisomer is an agonist at the AMPA and KA receptors, its (2 R,5' R) enantiomer interacts selectively with the NMDA receptors; the (2 S,5' R) stereoisomer is the only one capable to activate the mGluRs.