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The synthesis of medium-sized ring containing libraries using oxidative fragmentation and rearrangement strategies
Item metadata
dc.contributor.advisor | Westwood, Nicholas James | |
dc.contributor.author | Jones, Alan M. | |
dc.coverage.spatial | 285 | en |
dc.date.accessioned | 2009-04-14T14:50:12Z | |
dc.date.available | 2009-04-14T14:50:12Z | |
dc.date.issued | 2009-06-26 | |
dc.identifier | uk.bl.ethos.552211 | |
dc.identifier.uri | https://hdl.handle.net/10023/663 | |
dc.description.abstract | This 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.extent | 2675 bytes | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | en |
dc.publisher | University of St Andrews | |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.subject | Oxidative fragmentation | en |
dc.subject | Medium-sized rings | en |
dc.subject | Rearrangements | en |
dc.subject | Atropisomers | en |
dc.subject | Heterocycles | en |
dc.title | The synthesis of medium-sized ring containing libraries using oxidative fragmentation and rearrangement strategies | en |
dc.type | Thesis | en |
dc.contributor.sponsor | Biotechnology and Biological Sciences Research Council (BBSRC) | en |
dc.type.qualificationlevel | Doctoral | en |
dc.type.qualificationname | PhD Doctor of Philosophy | en |
dc.publisher.institution | The University of St Andrews | en |
dc.rights.embargodate | 2018-05-30 | en |
dc.rights.embargoreason | Thesis restricted in accordance with University regulations. Print and electronic copy restricted until 30th May 2018 | en |
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