Biocatalysis in organic synthesis

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dc.contributor.advisor Maguire, Anita R. en
dc.contributor.author Foley, Aoife M.
dc.date.accessioned 2019-02-05T09:55:59Z
dc.date.issued 2019
dc.date.submitted 2018
dc.identifier.citation Foley, A. M. 2019. Biocatalysis in organic synthesis. PhD Thesis, University College Cork. en
dc.identifier.endpage 234 en
dc.identifier.uri http://hdl.handle.net/10468/7431
dc.description.abstract The first chapter provides an overview of the use of biocatalysis for the synthesis of pharmaceutical intermediates and natural products. This review focuses, in particular, on the impact of recent developments in technologies which enable the increased use of biocatalysts. These developments include: • the immobilisation of biocatalysts to enhance stability and ease of use, and enabling use in combination with metal and organocatalysts leading to dynamic kinetic resolution, as well as in continuous flow. • discovery and development of novel enzymes using molecular biology for enzyme engineering and metagenomics. The second chapter describes the lipase-mediated kinetic resolution of 2-phenylalkanols by tuning the steric properties of the acyl group to control the efficiency and selectivity of the resolution. In contrast to literature reports, efficient resolution was achieved using short-chain acyl groups through careful process control and substrate modification. The effect of increased steric demand at the stereocentre was also explored. Chapter three describes proof of concept that a hydrolase-catalysed dynamic kinetic resolution of a lactol is possible. By taking advantage of the spontaneous racemisation of the unreacted starting material, the dynamic kinetic resolution was carried out without the need for a separate racemisation catalyst. While the kinetic resolution was effective in a model system, the biotransformation was inhibited by the introduction of a second, remote stereocentre. Chapter four describes a dynamic kinetic resolution of synthetically versatile nitroalcohols by combination of a lipase-mediated resolution and the reversible intramolecular nitroaldol (Henry) reaction. Significant challenges in effecting the combination of the base-mediated racemisation step and the lipase-mediated resolution step were encountered. Reaction engineering allowed design of a sequential one-pot reaction system which furnished the products with excellent enantioselectivity, and good diastereoselectivity. Chapter five describes the use of novel transaminases in the kinetic resolution of model amine substrates and pharmaceutical intermediates by oxidative deamination, including exploration of the substrate scope of these novel biocatalysts. While transaminase-mediated reductive amination is an attractive method for asymmetric synthesis of chiral amines, the reductive amination is generally thermodynamically disfavoured. Preliminary investigation of approaches to favour the reductive amination is described. The final chapter contains the full experimental details, including spectroscopic and analytical data of all the compounds synthesised in this project; details of chiral phase HPLC analysis are included in the appendix. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2019, Aoife M. Foley. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Biocatalysis en
dc.subject Enantioselective synthesis en
dc.title Biocatalysis in organic synthesis en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD en
dc.internal.availability Full text not available en
dc.check.info Restricted to everyone for five years en
dc.check.date 2024-02-04T09:55:59Z
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en
dc.internal.school Chemistry en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out No en
dc.thesis.opt-out false
dc.check.chapterOfThesis 1, 5
dc.check.embargoformat Apply the embargo to the e-thesis on CORA (If you have submitted an e-thesis and want to embargo it on CORA) en
ucc.workflow.supervisor a.maguire@ucc.ie
dc.internal.conferring Spring 2019 en
dc.internal.ricu Analytical and Biological Chemistry Research Facility en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/ en


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© 2019, Aoife M. Foley. Except where otherwise noted, this item's license is described as © 2019, Aoife M. Foley.
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