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

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.

Magnetic materials and soft-switched topologies for high-current DC-DC converters

The thesis is focused on the magnetic materials comparison and selection for high-power non-isolated dc-dc converters for industrial applications or electric, hybrid and fuel cell vehicles. The application of high-frequency bi-directional soft-switched dc-dc converters is also investigated. The thesis initially outlines the motivation for an energy-efficient transportation system with minimum environmental impact and reduced dependence on exhaustible resources. This is followed by a general overview of the power system architectures for electric, hybrid and fuel cell vehicles. The vehicle power sources and general dc-dc converter topologies are discussed. The dc-dc converter components are discussed with emphasis on recent semiconductor advances. A novel bi-directional soft-switched dc-dc converter with an auxiliary cell is introduced in this thesis. The soft-switching cell allows for the MOSFET's intrinsic body diode to operate in a half-bridge without reduced efficiency. The converter's mode-by-mode operation is analysed and closed-form expressions are presented for the average current gain of the converter. The design issues are presented and circuit limitations are discussed. Magnetic materials for the main dc-dc converter inductor are compared and contrasted. Novel magnetic material comparisons are introduced, which include the material dc bias capability and thermal conductivity. An inductor design algorithm is developed and used to compare the various magnetic materials for the application. The area-product analysis is presented for the minimum inductor size and highlights the optimum magnetic materials. Finally, the high-flux magnetic materials are experimentally compared. The practical effects of frequency, dc-bias, and converters duty-cycle effect for arbitrary shapes of flux density, air gap effects on core and winding, the winding shielding effect, and thermal configuration are investigated. The thesis results have been documented at IEEE EPE conference in 2007 and 2008, IEEE APEC in 2009 and 2010, and IEEE VPPC in 2010. A 2011 journal has been approved by IEEE Transactions on Power Electronics.