Synthesis, conformation and biological evaluation of the enantiomers of 3-fluoro-gamma-aminobutyric acid ((R)- and (S)-3F-GABA): an analogue of the neurotransmitter GABA.
Gamma-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).
Deniau
Gildas
G
School of Chemistry and Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews, Fife, KY16 9ST, Scotland, UK.
Slawin
Alexandra M Z
AM
Lebl
Tomas
T
Chorki
Fatima
F
Issberner
Jon P
JP
van Mourik
Tanja
T
Heygate
Judith M
JM
Lambert
Jeremy J
JJ
Etherington
Lori-An
LA
Sillar
Keith T
KT
O'Hagan
David
D
D000818:Animals; D001681:Biological Assay; D004341:Drug Evaluation; D018682:GABA Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D013237:Stereoisomerism; D014982:Xenopus laevis / Q000196:embryology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C526258:3-fluoro-gamma-aminobutryic acid; D018682:GABA Agents; D005680:gamma-Aminobutyric Acid