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dc.contributor.authorGeddis, Stephen Michael
dc.date.accessioned2018-06-27T11:55:43Z
dc.date.available2018-06-27T11:55:43Z
dc.date.issued2019-04-27
dc.date.submitted2018-04-05
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277551
dc.description.abstractNatural products have long been known for their broad range of useful therapeutic properties, and have been widely utilised in the field of medicine. This dissertation describes work towards the total synthesis of natural products possessing biological activity in two important areas. The first section concerns the total synthesis of six 4-quinolone natural products, four of which had never been synthesised before. These compounds were originally isolated from a soil bacterium of the genus Pseudonocardia, and bear intriguing structural resemblance to the Pseudomonas Quinolone Signal. This signalling molecule is vital to the quorum sensing activity of the human pathogen Pseudomonas aeruginosa, which is a phenomenon by which it regulates many of its virulence factors. These natural products possess the potential to disrupt this system, hence attenuating the pathogenicity of the bacteria. The routes that were developed are highly divergent, efficiently giving access to multiple natural products from mutual late stage intermediates. Key steps included regioselective epoxidation, palladium-catalysed heterocylisation and acid catalysed 1,3-transposition of an allylic alcohol. In the second section, attention turns towards the total synthesis of the complex sesquiterpene lactone 1β-Hydroxyalantolactone. The compound possesses five stereogenic centres, one of which is quaternary, alongside a challenging tricyclic core scaffold. Previous biological studies have revealed a range of intriguing properties, including anti-inflammatory and anti-tumour activity. The chosen route utilises as its key step the catalytic desymmetrisation of a diene which was itself accessed by Birch reduction chemistry. Whilst the synthesis is as yet incomplete, access was granted to a key intermediate encompassing around half of the stereocentres present in the natural product.
dc.description.sponsorshipCHESS Scholarship Department of Chemistry
dc.language.isoen
dc.rightsAll rights reserved
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectTotal Synthesis
dc.subjectAntimicrobial
dc.subjectQuorum Sensing
dc.subjectAnti-inflammatory
dc.subjectAnti-tumour
dc.subjectTerpenes
dc.subject4-quinolones
dc.subjectNatural Products
dc.titleThe Total Synthesis of Pseudonocardia sp. Quinolone Natural Products and Studies Towards the Total Synthesis of 1β-Hydroxyalantolactone
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentChemistry
dc.date.updated2018-06-27T10:28:24Z
dc.rights.generalP. 19, Figure of Bacterial Growth Curves, copyright holder is John Wiley & Sons, Inc.
dc.identifier.doi10.17863/CAM.24866
dc.publisher.collegeCorpus Christi
dc.type.qualificationtitlePhD in Chemistry
cam.supervisorSpring, David
cam.thesis.fundingfalse
rioxxterms.freetoread.startdate2019-06-27


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