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

doi:10.1016/S0957-4166(02)00412-3

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 journal › Article › peer-review

26 Scopus citations

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 language	English (US)
Pages (from-to)	1609-1614
Number of pages	6
Journal	Tetrahedron Asymmetry
Volume	13
Issue number	15
DOIs	https://doi.org/10.1016/S0957-4166(02)00412-3
State	Published - Aug 14 2002
Externally published	Yes

ASJC Scopus subject areas

Catalysis
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.1016/S0957-4166(02)00412-3

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

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.",

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AU - Vitharana, Dilrukshi

AU - France, Jessica E.

AU - Scarpetti, David

AU - Bonneville, George W.

AU - Majer, Pavel

AU - Tsukamoto, Takashi

PY - 2002/8/14

Y1 - 2002/8/14

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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