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Synthesis, Conformation and Biological Evaluation of the Enantiomers of 3‐Fluoro‐γ‐Aminobutyric Acid (( R )‐ and ( S )‐3F‐GABA): An Analogue of the Neurotransmitter GABA
Author(s) -
Deniau Gildas,
Slawin Alexandra M. Z.,
Lebl Tomas,
Chorki Fatima,
Issberner Jon P.,
van Mourik Tanja,
Heygate Judith M.,
Lambert Jeremy J.,
Etherington LoriAn,
Sillar Keith T.,
O'Hagan David
Publication year - 2007
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700371
Subject(s) - enantiomer , aminobutyric acid , chemistry , gamma aminobutyric acid , stereochemistry , amino acid , conformational isomerism , gaba receptor , gabaa receptor , receptor , molecule , biochemistry , organic chemistry
γ‐Aminobutyric acid or GABA ( 1 ) is one of the major inhibitory amino acid neurotransmitters of the central nervous system. This article describes the first synthesis of both the ( R )‐ and ( S )‐ enantiomers of 3‐fluoro‐GABA ( 2 , 3F‐GABA). DFT calculations were carried out in a continuum solvent model (PCM–B3LYP) to estimate the preferred conformations of 3F‐GABA in aqueous solution. NMR coupling constants were calculated for each conformer and were then used to simulate the NMR spectra to evaluate the solution conformation of 3F‐GABA. A preliminary evaluation of the 3F‐GABA enantiomers shows that they act similarly as agonists of cloned GABA A receptors; however, they behave quite differently in a whole animal ( Xenopus laevis tadpole model).