Excitatory amino acid receptor ligands: Asymmetric synthesis, absolute stereochemistry and pharmacology of ( R)- and ( S)-homoibotenic acid
The ( R)- and ( S)-forms of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) were synthesized, using ( S)-BOC-phenylalanine as a chiral auxiliary and their absolute stereochemistry correlated with that of ( R)-BrHIBO. The enantiomeric excesses for ( R)-HIBO ( 1) (> 99.5%...
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Published in | Bioorganic & medicinal chemistry Vol. 3; no. 5; pp. 553 - 558 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.05.1995
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Subjects | |
Online Access | Get full text |
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Summary: | The (
R)- and (
S)-forms of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) were synthesized, using (
S)-BOC-phenylalanine as a chiral auxiliary and their absolute stereochemistry correlated with that of (
R)-BrHIBO. The enantiomeric excesses for (
R)-HIBO (
1) (> 99.5%) and (
S)-HIBO (
2) (99.5%) were determined using chiral HPLC. Whereas compounds
1 and
2 were equipotent inhibitors of the binding of [
3H]glutamic acid in the presence of calcium chloride, 2 showed AMPA agonist activity and 1 very weak NMDA agonist activity.
The enantiomers of homoibotenic acid (HIBO) were synthesized through diastereomeric intermediates. The absolute stereochemistry was determined chemically, the enantiomeric excess by chiral HPLC and pharmacology studied by receptor binding and electrophysiological experiments. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/0968-0896(95)00044-H |