Synthesis and NMD A Antagonistic Properties of the Enantiomers of 4-(3-phosphonopropyl)piperazine-2-carboxylic acid (CPP) and of the unsaturated analogue (E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CPP-ene)

The (R)‐ and (s)‐enantiomers of 4‐(3‐phosphonopropyl)piperazine‐2‐carboxylic acid (D‐ and L‐CPP, resp.; 15 and 16, resp.), and of its unsaturated analogue (E)‐4‐(3‐phosphonoprop‐2‐enyl)piperazine‐2‐carboxylic acid (D‐ and L‐CPP‐ene, resp.; 13 and 14, resp.) were prepared. The absolute configuration of the enantiomers was determined by a chemical correlation of the menthyl ester 7 with D‐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, competitive NMDA antagonist known to date.