Studies in asymmetric and heterocyclic synthesis: I. chiral ketones II. Quinolones III. Trifluoromethylated pyrones

Simple item page
dc.check.embargoformatNot applicableen
dc.check.infoNo embargo requireden
dc.check.opt-outNot applicableen
dc.check.reasonNo embargo requireden
dc.check.typeNo Embargo Required
dc.contributor.advisorMcglacken, Gerard P.en
dc.contributor.authorClarke, Sarah L.
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.contributor.funderPfizer Irelanden
dc.date.accessioned2016-09-16T08:17:40Z
dc.date.available2016-09-16T08:17:40Z
dc.date.issued2015
dc.date.submitted2015
dc.description.abstractThis thesis is split into three sections based on three different areas of research. In the first section, investigations into the α-alkylation of ketones using a novel chiral auxiliary is reported. This chiral auxiliary was synthesised containing a pyrrolidine ring in the chiral arm and was applied in the preparation of α-alkylated ketones which were obtained in up to 92% ee and up to 63% yield over two steps. Both 3-pentanone and propiophenone based ketones were used in the investigation with a variety of both alkyl and benzyl based electrophiles. The novel chiral auxiliary was also successful when applied to Michael and aldol reactions. A diamine precursor en route to the chiral auxiliary was also applied as an organocatalyst in a Michael reaction, with the product obtained in excellent enantioselectivity. In the second section, investigations into potential anti-quorum sensing molecules are reported. The bacteria Pseudomonas aeruginosa is an antibiotic-resistant pathogen that demonstrates cooperative behaviours and communicates using small chemical molecules in a process termed quorum sensing. A variety of C-3 analogues of the quorum sensing molecules used by P. aeruginosa were synthesised. Expanding upon previous research within the group, investigations were carried out into alternative protecting group strategies of 2-heptyl-4-(1H)- quinolone with the aim of improving the yields of products of cross-coupling reactions. In the third section, investigations into fluorination and trifluoromethylation of 2-pyrones, pyridones and quinolones is reported. The incorporation of a fluorine atom or a trifluoromethyl group into a molecule is important in pharmaceutical drug discovery programmes as it can lead to increased lipophilicity and bioavailability, however late-stage incorporation is rarely reported. Both direct fluorination and trifluoromethylation were attempted. Eight trifluoromethylated 2-pyrones, five trifluoromethylated 2-pyridones and a trifluoromethylated 2-quinolone were obtained in a late-stage synthesis from their respective iodinated precursors using methyl fluorosulfonyldifluoroacetate as a trifluoromethylating reagent.en
dc.description.sponsorshipPfizer Ireland (Pfizer Process Development Centre Cork under the Enterprise Partnership Scheme)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationClarke, S. L. 2015. Studies in asymmetric and heterocyclic synthesis: I. chiral ketones II. Quinolones III. Trifluoromethylated pyrones. PhD Thesis, University College Cork.en
dc.identifier.endpage394en
dc.identifier.urihttps://hdl.handle.net/10468/3091
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2015, Sarah L. Clarke.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectAsymmetric synthesisen
dc.subjectTrifluoromethylationen
dc.subjectQuinolonesen
dc.subjectChiral auxiliaryen
dc.subjectPyroneen
dc.subjectPyridoneen
dc.subjectAlpha alkylated ketoneen
dc.thesis.opt-outfalse
dc.titleStudies in asymmetric and heterocyclic synthesis: I. chiral ketones II. Quinolones III. Trifluoromethylated pyronesen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorg.mcglacken@ucc.ie
Files
Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
Abstract.pdf
Size:
100.59 KB
Format:
Adobe Portable Document Format
Description:
Abstract
Thumbnail Image
Name:
ClarkeSL_PhD2015.pdf
Size:
16.19 MB
Format:
Adobe Portable Document Format
Description:
Full Text E-thesis
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
5.62 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Doctoral Theses
Chemistry - Doctoral Theses
College of Science, Engineering and Food Science - Doctoral Theses