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dc.contributor.advisorO'Hagan, David
dc.contributor.authorMoraux, Thomas
dc.description.abstractChapter 1 gives an overview of the fluorine chemistry field, from its early developments to recent applications in medicinal chemistry. The development of asymmetric electrophilic or nucleophilic installation of fluorine in organic molecules is highlighten. Chapter 2 of this thesis discusses the enantioselective synthesis of α-fluoroamides. The study is applied to the synthesis of fluoroenantiomers of the bioactive molecule capsaicin and short-chain analogues. The biological activity of these compounds is assayed with the TRPV1 receptor. Results show that enantioselective α-fluoroamides (R)-97, (R)-99 and (S)-99 can generate differentiated biological responses, from TRPV1 agonists to TRPV1 antagonists. Chapter 3 focuses on the optimisation and development of 2-(aminomethyl)piperidine (R)-251 dihydrochloride. The development of 2-(aminomethyl)piperidine (R)-251 as its ditetrafluoroborate salt proved to offer excellent reactivity and solubility for the preparation of derivatives. This tetrafluoroborate salt was used to improve the syntheses of organocatalysts 2,2,2-trifluoro-N-(piperidin-2-ylmethyl)acetamide 363 and 4-methyl-N-(piperidin-2-ylmethyl)benzenesulfonamide 364.The catalytic properties of these latter two molecules for asymmetric Mannich reaction is demonstrated. Both (R)-363 and (R)-364 show up to 86% ee, in a typical 20 mol% loading, but loading of (R)-363 as low as 5 mol% still induces the catalysis.en_US
dc.publisherUniversity of St Andrews
dc.subjectAsymmetric fluooroorganic chemistryen_US
dc.subjectMedicinal chemistryen_US
dc.subjectTRPV1 receptoren_US
dc.subject2-(aminomethyl)piperidine ditetrafluoroborateen_US
dc.subject.lcshOrganofluorine compoundsen_US
dc.subject.lcshOrganofluorine compounds--Synthesisen_US
dc.subject.lcshPharmaceutical chemistryen_US
dc.subject.lcshAsymmetry (Chemistry)en_US
dc.titleSynthesis and evaluation of α-fluoro analogues of capsaicin and 2-(aminomethyl)piperidine derivativesen_US
dc.contributor.sponsorEngineering and Physical Sciences Research Council (EPSRC)en_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US

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