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dc.contributor.authorWadoux, Rudy
dc.coverage.spatial103en_US
dc.date.accessioned2015-03-26T10:23:55Z
dc.date.available2015-03-26T10:23:55Z
dc.date.issued2014-06-25
dc.identifier.urihttp://hdl.handle.net/10023/6339
dc.description.abstractThis thesis explores the synthesis and use of biologically active fluorinated organic compounds. Muscimol is the neuroactive species of the psychoactive mushroom Amanita muscaria. It binds at the same site as GABA on GABA[sub]A receptors, and fluorination of muscimol is therefore of particular interest, as it could allow the imaging of GABA binding sites by positron emission tomography using the fluorine-18 isotope. Chapter 1 describes research towards the synthesis of fluoromuscimol 33. Two approaches were taken. The first involved cyclisation of a fluorinated precursor, while the second aimed at the introduction of fluorine using a pre-existing synthesis of muscimol. ¹H and ¹⁹F NMR evidence of the formation of a fully protected fluoromuscimol was observed after a key lithium-halogen exchange step, followed by in situ fluorination. Previous work in the group allowed the synthesis of chiral [7-²H₁]-benzyl fluoride with high enantiopurity. In Chapter 2, (S)- and (R)-[7-²H₁]-benzyl fluorides (S)-78 and (R)-78 were resynthesized from benzaldehyde in two steps. They were used in competition experiments to explore the cryptic stereochemistry of the unspecific peroxygenase of Agrocybe aegerita, showing a weak preference for a pro-(S) proton abstraction in the first stage of the mechanism of benzyl fluoride oxidation. Moreover, an oxidation reaction of these benzyl fluorides to obtain enantiomers (S)-82 and (R)-82 of chiral [2-²H₁]-fluoroacetate was improved to remove acetate pollution in the product. Finally, chiral analysis of the hexyl ester of these enantiomeric fluoroacetates by a specific ²H NMR technique established their enantiopurity.en_US
dc.language.isoenen_US
dc.publisherUniversity of St Andrews
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectFluoromuscimolen_US
dc.subjectMuscimolen_US
dc.subjectGABA agonisten_US
dc.subjectStereoselectiveen_US
dc.subjectDeoxofluorinationen_US
dc.subjectBenzyl fluorideen_US
dc.subjectIsoxazoleen_US
dc.subjectPositron emission tomographyen_US
dc.subject.lccQD412.F1W2
dc.subject.lccQD412.F1W2
dc.subject.lcshOrganofluorine compoundsen_US
dc.subject.lcshOrganofluorine compounds--Synthesisen_US
dc.subject.lcshFluorinationen_US
dc.subject.lcshChiralityen_US
dc.subject.lcshOxidoreductasesen_US
dc.titleApproaches to the synthesis of fluoromuscimol and applications of the enantiomers of [7-²H₁]-benzyl fluoride as chiral probes for enzyme reactionsen_US
dc.typeThesisen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnameMPhil Master of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.rights.embargodateElectronic copy restricted until 7th May 2016en_US
dc.rights.embargoreasonThesis restricted in accordance with University regulationsen_US


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