New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.

Elizabeth Bowen and the art of visuality

This thesis is the first sustained assessment of Elizabeth Bowen’s writing from a visual perspective. By first compiling a visual biography of the author, I argue that Bowen’s responsiveness to art, her relationships with artists, and her knowledge of modern and traditional aesthetics are formative influences on her work. Investigating her assertion that she was a “visual writer,” my discussion develops into an examination of her technique of “verbal painting” through which she reinvents traditional visual modes as a personal modernist idiom. Close textual analysis of Bowen’s fictions forms the dominant methodology of this thesis and facilitates my delineation of her engagement with the Futurist and Surrealist aesthetics in addition to broader aspects of her visuality, including her treatment of the “vividly visual” dream-state to the distinct ocularcentricity of her writing. Ultimately, this thesis seeks to advance our knowledge of Bowen’s visual method and to offer a new approach in which to nuance our understanding of her modernism

A phenomenological study to explore individuals’ experience of depression

Numerous epidemiological findings suggest that we live in an era that can only be described as the “age of melancholy” in that more and more individuals are diagnosed with depression every year. The aim of this study was to gain a phenomenological understanding of how individuals who experienced depression understood and made sense of their experience of depression through a methodology of interpretative phenomenological analysis. In-depth semi-structured interviews explored the lived experience of depression for eight individuals and identified how social discourses contributed to their understanding. Following rigorous analysis of twelve interview transcripts, data was broken down into four recurrent superordinate themes which related directly to how individuals made sense of their experience of depression; The Descent; The Worlds Conversations and Me - Engagement with Social Discourses; Broken Self - Transforming the Self; Embracing myself and my Mind - Transformation of the Self. Further interrogative analysis identified how some social discourses communicated by healthcare professionals, the media and academia, contributed to individuals experiencing an additional layer of distress, namely meta-distress which in essence is distress about distress.

A philosophy of performance, politics and composition

This thesis discusses socio-political issues worldwide through philosophical approaches to performance, politics and composition. My research also discuss sound decisions which I regard to be simultaneously an outlet for personal expression, as well as a practical tool to inspire a socio-political change in society. Although the latter is paramount to the methodology of the project, the sound cannot be regarded in isolation as a “political composition”. It can only become truly functional in a political sense through interaction with other art forms, within the context of a specific place and time. My portfolio for this project is of two socio-political projects which are my chief concern. The first project concerns the Israeli-Palestinian conflict. I named this project PATH. PATH aims to foster and expand peaceful thought between Jewish and Palestinian civilians in Israel-Palestine. Through performance art, PATH spreads a message of acceptance, unity and brotherhood between our peoples. Above all, PATH demands and end to intolerance, hatred and violence among all the inhabitants of the State of Israel. The second project concerns women’s rights globally. I have realised that although we have come a long way in our struggle for rights for women, great challenges remain. There is a need to unite women and men against a form of oppression that discriminates against 50% of the world’s population. I called this project, For Utopia.

Market-oriented new product development of health promoting foods for the ageing population

Major factors influencing food development and food marketing strategies in global market places at present can be attributable to the changing age structure of the population. The significant shifts in global age structure will inevitably lead to the number of people aged 60 reaching an all-time high of one billion by the year 2020. The rapidly growing population of ageing people globally represents a large, neglected and very much under-developed category within the Food Industry. The primary focus of this study was the integration of knowledge creation techniques at early NPD stages, for the development of market-oriented new health promoting foods for the ageing population. The methodology of this study was centered on an exploratory sequential mixed methods strategy. Stage one of the study involved in-depth semi-structured interviews with 16 Stakeholders to facilitate the need identification stage of the NPD process. The main outputs identified were the need for: the fortification of foods for a preventative nutrition approach, the development of foods that targeted age-related conditions such as cognitive, heart, gut and bone health, the integration of ageing compensatory packaging adaptations and the creation of marketing messages with an active lifestyle message. Stage two consisted of a market-oriented computer assisted NPD technique, a user centered design interaction (UCD) to integrate consumers as co-creators throughout the idea generation stage of the NPD process. The most important product attributes identified in this stage included: products targeted at brain and cognitive health, liquid based beverages, easy to use packaging with environmentally friendly elements, simplistic marketing with a clear focus on health not age and realistic health claims constructed with consumer friendly terminology. Finally, Stage three used an abbreviated means-end chain (MEC) analysis to complete the concept development stage of the NPD process. This stage identified commercial information that could be used by food firms for the development of positioning and communication strategies. Equally, the information generated could be of high strategic importance to governments, policy makers, health professionals and medical professionals. The values and goals listed in this stage included: better overall health, active lifestyle, optimum nutrition and wellbeing feelings. Overall, this research illustrated that knowledge creation techniques can assist firms in the development of market-oriented health promoting foods for the ageing population.

Monitoring and modelling the morphodynamic evolution of a breached barrier beach system

Predicting the evolution of a coastal cell requires the identification of the key drivers of morphology. Soft coastlines are naturally dynamic but severe storm events and even human intervention can accelerate any changes that are occurring. However, when erosive events such as barrier breaching occur with no obvious contributory factors, a deeper understanding of the underlying coastal processes is required. Ideally conclusions on morphological drivers should be drawn from field data collection and remote sensing over a long period of time. Unfortunately, when the Rossbeigh barrier beach in Dingle Bay, County Kerry, began to erode rapidly in the early 2000’s, eventually leading to it breaching in 2008, no such baseline data existed. This thesis presents a study of the morphodynamic evolution of the Inner Dingle Bay coastal system. The study combines existing coastal zone analysis approaches with experimental field data collection techniques and a novel approach to long term morphodynamic modelling to predict the evolution of the barrier beach inlet system. A conceptual model describing the long term evolution of Inner Dingle Bay in 5 stages post breaching was developed. The dominant coastal processes driving the evolution of the coastal system were identified and quantified. A new methodology of long term process based numerical modelling approach to coastal evolution was developed. This method was used to predict over 20 years of coastal evolution in Inner Dingle Bay. On a broader context this thesis utilised several experimental coastal zone data collection and analysis methods such as ocean radar and grain size trend analysis. These were applied during the study and their suitability to a dynamic coastal system was assessed.