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

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 (2S,5′S) stereoisomer is an agonist at the AMPA and KA receptors, its (2R,5′R) enantiomer interacts selectively with the NMDA receptors; the (2S,5′R) stereoisomer is the only one capable to activate the mGluRs.