ISSN:
0899-0042
Schlagwort(e):
diastereomeric salt resolution
;
chiral HPLC
;
enantiomeric purity
;
absolute stereochemistry
;
X-ray crystallography
;
NMDA receptor antagonist
;
AMPA receptor antagonist
;
Chemistry
;
Organic Chemistry
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Chemie und Pharmazie
Notizen:
We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation using N-BOC protected ATAA and (R)- and (S)-phenylethylamine. Enantiomeric purities (ee 〉 98%) of (R)- and (S)-ATAA were determined using the Crownpak CR(-) and CR(+) columns, respectively. The absolute configuration of (R)-ATAA was established by an X-ray crystallographic analysis of the (R)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 〉 100 μM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 ± 5 μM and 57 ± 1 μM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation (Ki 〉 1,000 μM). Chirality 9:529-536, 1997. © 1997 Wiley-Liss, Inc.
Zusätzliches Material:
8 Ill.
Materialart:
Digitale Medien
