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

Abstract

Abstract 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 [ 3 H]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.