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)

✍ Scribed by Bernard Aebischer; Peter Frey; Hans-Peter Haerter; Paul L. Herrling; Werner Mueller; Henry J. Olverman; Jeffrey C. Watkins

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: German
• Weight: 552 KB
• Volume: 72
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19890720522

✦ Synopsis

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 o-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), o-CPP-ene appears to be the most potent, enantiomerically pure, competitive NMDA antagonist known to date. ') CPP is the abbreviation of the name 3-(2-carboxypiperazin-4-yl)propyl-1 -phosphonic acid that is currently used in the literature. We prefer the nomenclature employed by Chemical Abstracts that considers the carboxylic-acid moiety as the principal group.