Synthesis and biological evaluation of (R)- and (S)-2-(phosphonomethyl)pentanedioic acids as inhibitors of glutamate carboxypeptidase II

Dilrukshi Vitharana, Jessica E. France, David Scarpetti, George W. Bonneville, Pavel Majer, Takashi Tsukamoto

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1609-1614
Number of pages6
JournalTetrahedron Asymmetry
Volume13
Issue number15
DOIs
StatePublished - Aug 14 2002

ASJC Scopus subject areas

  • Catalysis
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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