title: 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.
abstract: 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).
authors.affiliation: School of Chemistry and Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews, Fife, KY16 9ST, Scotland, UK.
authors.forename: Gildas
authors.initials: G
authors.lastname: Deniau
authors.forename: Alexandra M Z
authors.initials: AM
authors.lastname: Slawin
authors.forename: Tomas
authors.initials: T
authors.lastname: Lebl
authors.forename: Fatima
authors.initials: F
authors.lastname: Chorki
authors.forename: Jon P
authors.initials: JP
authors.lastname: Issberner
authors.forename: Tanja
authors.initials: T
authors.lastname: van Mourik
authors.forename: Judith M
authors.initials: JM
authors.lastname: Heygate
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Lambert
authors.forename: Lori-An
authors.initials: LA
authors.lastname: Etherington
authors.forename: Keith T
authors.initials: KT
authors.lastname: Sillar
authors.forename: David
authors.initials: D
authors.lastname: O'Hagan
mesh_terms: 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
chemical_list: C526258:3-fluoro-gamma-aminobutryic acid; D018682:GABA Agents; D005680:gamma-Aminobutyric Acid