Both enantiomers of 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a potent and selective inhibitor of glutamate carboxypeptidase II (GCP II), were successfully prepared through the resolution of racemic 2-(hydroxyphosphinoylmethyl)pentanedioic acid dibenzyl ester with yohimbine and (S)-α-methylbenzylamine. The enantiomeric purity of the resolved phosphinic acid was measured by coupling it to (-)-menthol and analyzing the resulting ester by 31P NMR. The absolute configuration of the 2-carbon atom in the resolved phosphinic acid was determined by X-ray crystallographic studies. Optically pure 2-PMPA was obtained by oxidation of the resolved phophinic acid to the phosphonic acid followed by catalytic hydrogenolysis. The biological activity of each enantiomer of 2-PMPA will also be described.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry