The synthesis and biological evaluation of lanostane and cholestane-type natural products

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dc.contributor.advisor Collins, Stuart G. en O'Keeffe, Roisin J. M. 2014-03-31T14:34:14Z 2014 2014
dc.identifier.citation O'Keeffe, R. J. M. 2014. The synthesis and biological evaluation of lanostane and cholestane-type natural products. PhD Thesis, University College Cork. en
dc.identifier.endpage 312
dc.description.abstract The main objective of this thesis is to outline the synthetic chemistry involved in the preparation of a range of novel lanostane and cholestane derivatives, and subsequent investigation into their biological activity in cancer cells. The biological results obtained throughout the project have driven the strategic synthesis of new compounds, in an effort to optimise the anti cancer potential of lanostane and cholestane derivatives. The first chapter begins with an overview of steroidal compounds and details a literature review of the natural sources of these moieties, as well as their biosynthesis and reported synthetic derivatives. The biological activity of interesting natural and synthetic analogues is also discussed. In addition, an insight into some currently prescribed pharmaceutical compounds, with functional groups relevant to this project, is presented. The second chapter discusses the methods employed for the synthesis of these novel lanostane and cholestane derivatives, and comprises three main sections. Firstly, various oxidation products of lanosterol are synthesised, mainly via epoxidations of the C-8,9 and C- 24,25 alkenes, and also allylic oxidations at these positions. Secondly, amine derivatives of lanosterol are formed by cleaving the lanostane side chain, thereby yielding a new cholestane nucleus, and performing several reductive aminations on the resulting key aldehyde intermediates. Various amines such as piperidine, morpholine, diethylamine and aniline are employed in the reductive amination reactions to yield novel cholestane steroids with amine side chains. Finally, starting from stigmasterol and proceeding with the same methodology of cleaving the steroidal side chain and subsequently performing reductive aminations, novel cholestane derivatives of the biologically active amines are synthesised. The cytotoxicity of these compounds against CaCo-2 and U937 cell lines is presented in terms of percentage viability of cells, IC50 value and apoptosis. The MTT assay is used to determine the percentage viability of cells, and the IC50 data is generated from the MTT results. Apoptosis is measured in terms of fold increase relative to a carrier control. In summary, the compounds formed are discussed in terms of chemical synthesis, spectroscopic interpretation and biological activity. The main reaction pathways involved in the chemistry within this project are various oxidations and reductive amination. The final chapter is a detailed account of the full experimental procedures for the compounds synthesised during this work, including characterisation using spectroscopic and analytical data. en
dc.description.sponsorship Department of Fisheries, Agriculture and the Marine (FIRM) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Roisin J. M. O'Keeffe. en
dc.rights.uri en
dc.subject Lanostane en
dc.subject Cholestane en
dc.subject Natural products en
dc.subject.lcsh Steroids en
dc.title The synthesis and biological evaluation of lanostane and cholestane-type natural products en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text available en
dc.description.version Accepted Version
dc.contributor.funder Department of Fisheries, Agriculture and the Marine, Ireland en
dc.description.status Not peer reviewed en 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.embargoformat Both hard copy thesis and e-thesis en
dc.internal.conferring Summer Conferring 2014 en

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© 2014, Roisin J. M. O'Keeffe. Except where otherwise noted, this item's license is described as © 2014, Roisin J. M. O'Keeffe.
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