AbstractThe (R)‐ and (s)‐enantiomers of 4‐(3‐phosphonopropyl)piperazine‐2‐carboxylic acid (D‐ andL‐CPP, resp.;15and16, resp.), and of its unsaturated analogue (E)‐4‐(3‐phosphonoprop‐2‐enyl)piperazine‐2‐carboxylic acid (D‐ andL‐CPP‐ene, resp.;13and14, resp.) were prepared. The absolute configuration of the enantiomers was determined by a chemical correlation of the menthyl ester 7 withD‐asparagine. The affinity of these derivatives for the NMDA receptor was determined by displacement of [3H]CPP in rat cerebral cortical membranes. In two functional tests (the frog hemisected spinal cord preparation and the sodium efflux test from rat brain slices),D‐CPP‐ene appears to be the most potent, enantiomerically pure,