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dc.contributor.advisorWestwood, Nicholas James
dc.contributor.authorJones, Alan M.
dc.coverage.spatial285en
dc.date.accessioned2009-04-14T14:50:12Z
dc.date.available2009-04-14T14:50:12Z
dc.date.issued2009-06-26
dc.identifieruk.bl.ethos.552211 
dc.identifier.urihttps://hdl.handle.net/10023/663
dc.description.abstractThis thesis describes the development of a synthetic route that encodes a library of compounds containing medium-sized ring systems, with particular emphasis on the use of oxidative fragmentation and rearrangement strategies. Chapter 1 introduces diversity oriented synthesis (DOS) with particular emphasis on medium-sized ring synthesis and fragmentation/rearrangement protocols to achieve diversity. A more detailed discussion of oxidative fragmentation and rearrangement methods is also presented. Chapter 2 describes strategies for the synthesis of a collection of heterocyclic compounds known as diazabenz[e]aceanthrylenes. The scope of the reaction was explored as a function of a range of substituents and of the ring size of the N-aryl lactam that was used. Spectroscopic observations associated with this set of compounds are also discussed. Chapter 3 describes the development of an m-CPBA-mediated oxidative fragmentation of the diazabenz[e]aceanthrylenes. Analysis of the products from these reactions revealed the presence of atropisomerism due to restricted rotation about the N sp²-C(aryl) sp² bond. Chapter 4 focuses on a related example of oxidative fragmentation from the literature. A previously overlooked stereogenic axis is explored in this system using X-ray crystallographic analysis and variable temperature ¹H NMR spectroscopy. Reinterpretation of the reported mechanism-probing experiment led to the isolation of an alternative isomeric product and an improved interpretation for the reaction outcome is presented. Variable temperature ¹H NMR spectroscopic experiments revealed the energy barrier to racemisation in the medium-sized ring-containing analogues and based on this data the mode of ring inversion is discussed. Chapter 5 describes three rearrangements of the medium-sized ring system created in Chapter 3 including the formation of an azepinoindole ring structure, a Favorskii reaction and spiro-oxindole synthesis. A rationalisation for these reaction outcomes is included along with experimental support of mechanistic proposals. The generality and scope of the reactions are demonstrated including a nucleophile screen. Chapter 6 describes the synthesis of a library of 69 compounds consisting of examples of the core structures described in Chapters 2, 3 and 5. A discussion of the selection process and adaption of the protocol to parallel synthesis is presented. This chapter concludes with preliminary screening of the library against a variety of strains of yeasts and bacteria.en
dc.format.extent2675 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherUniversity of St Andrews
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subjectOxidative fragmentationen
dc.subjectMedium-sized ringsen
dc.subjectRearrangementsen
dc.subjectAtropisomersen
dc.subjectHeterocyclesen
dc.titleThe synthesis of medium-sized ring containing libraries using oxidative fragmentation and rearrangement strategiesen
dc.typeThesisen
dc.contributor.sponsorBiotechnology and Biological Sciences Research Council (BBSRC)en
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen
dc.publisher.institutionThe University of St Andrewsen
dc.rights.embargodate2018-05-30en
dc.rights.embargoreasonThesis restricted in accordance with University regulations. Print and electronic copy restricted until 30th May 2018en


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