Strategies towards the synthesis of prostaglandin analogues

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dc.contributor.authorHaupt, Hayley Claireen_ZA
dc.date.accessioned2014-08-13T14:26:29Z
dc.date.available2014-08-13T14:26:29Z
dc.date.issued2006en_ZA
dc.descriptionIncludes bibliographical references (leaves 173-179).en_ZA
dc.description.abstractDifferent strategies for the synthesis of cyclopentenone prostaglandins and their analogues have been explored. The key transformation critical to the success of each of the described routes involves a Lewis-acid mediated retro Diels-Alder (rDA) reaction as the final step in liberating a 4, 5 disubstituted cyclopent-2-ene-1- one under extremely mild conditions. The first approach involves installation of the a-chain followed by base-mediated methodology to affect regiospecific enolate generation. Effective trapping of the enolate generates the requisite target. Within the context of this strategy both 2- and 3-component coupling protocols have been elaborated. Having demonstrated that the a- and p- sidechains could be installed, the key rDA reaction has been used to generate target analogues. The second approach utilizes a Diels-Alder cycloaddition reaction as the key step. The thermal and Lewis-acid catalysed Diels-Alder reactions between tricyclo[5.2.1.0 2,6]dec-8-en-3-one and 3-hydroxytricyclo[5.2.1.0 2,6]dec-8-ene with butadiene and butadiene sulfone have been investigated. While reaction between the enone and the dienophiles proved to be low yielding, the reaction between the allylic alcohol and butadiene sulfone proceeded readily and in high yield. The derived cycloadduct represents a late-stage intermediate for the synthesis of isoprostanes. Methodologies to perform cis-hydroxylation followed by oxidative cleavage of the cyclohexene moiety have been successfully implemented. Finally, a synthesis was designed for generating oxygen analogues of the prostaglandin targets.en_ZA
dc.identifier.apacitationHaupt, H. C. (2006). <i>Strategies towards the synthesis of prostaglandin analogues</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/6312en_ZA
dc.identifier.chicagocitationHaupt, Hayley Claire. <i>"Strategies towards the synthesis of prostaglandin analogues."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2006. http://hdl.handle.net/11427/6312en_ZA
dc.identifier.citationHaupt, H. 2006. Strategies towards the synthesis of prostaglandin analogues. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Haupt, Hayley Claire AB - Different strategies for the synthesis of cyclopentenone prostaglandins and their analogues have been explored. The key transformation critical to the success of each of the described routes involves a Lewis-acid mediated retro Diels-Alder (rDA) reaction as the final step in liberating a 4, 5 disubstituted cyclopent-2-ene-1- one under extremely mild conditions. The first approach involves installation of the a-chain followed by base-mediated methodology to affect regiospecific enolate generation. Effective trapping of the enolate generates the requisite target. Within the context of this strategy both 2- and 3-component coupling protocols have been elaborated. Having demonstrated that the a- and p- sidechains could be installed, the key rDA reaction has been used to generate target analogues. The second approach utilizes a Diels-Alder cycloaddition reaction as the key step. The thermal and Lewis-acid catalysed Diels-Alder reactions between tricyclo[5.2.1.0 2,6]dec-8-en-3-one and 3-hydroxytricyclo[5.2.1.0 2,6]dec-8-ene with butadiene and butadiene sulfone have been investigated. While reaction between the enone and the dienophiles proved to be low yielding, the reaction between the allylic alcohol and butadiene sulfone proceeded readily and in high yield. The derived cycloadduct represents a late-stage intermediate for the synthesis of isoprostanes. Methodologies to perform cis-hydroxylation followed by oxidative cleavage of the cyclohexene moiety have been successfully implemented. Finally, a synthesis was designed for generating oxygen analogues of the prostaglandin targets. DA - 2006 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 T1 - Strategies towards the synthesis of prostaglandin analogues TI - Strategies towards the synthesis of prostaglandin analogues UR - http://hdl.handle.net/11427/6312 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/6312
dc.identifier.vancouvercitationHaupt HC. Strategies towards the synthesis of prostaglandin analogues. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2006 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/6312en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherChemistryen_ZA
dc.titleStrategies towards the synthesis of prostaglandin analoguesen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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