Synthesis of the C(1)-C(9) fragment of disorazole C1 and novel heterocyclic analogues

A highly convergent strategy for the synthesis of the antitubulin polyketide disorazole C1 is proposed based around the alkyne precursor I, featuring a novel Evans-Tishchenko/ring closing alkyne metathesis approach. Due to the inherent symmetry of the molecule this retrosynthesis leads to two fragments: a β- hydroxyketone II and the oxazole C(1)-(9) fragment III. A review of previous syntheses of disorazole C1 and established structure activity relationships (SARs) highlights a gap in current knowledge relating to the role of the oxazole in tubulin binding. Therefore, the focus of this research has been towards developing new routes for the synthesis of the C(1)-C(9) fragment that can be adapted to the synthesis of heterocyclic analogues to further establish the SAR of disorazole C1. Chapter 2 focuses on a disconnection at the C(5)-C(6) bond and a novel synthesis of the racemic C(1)-C(9) fragment has been achieved via a lithiation of methyl 2- methyl-1,3-oxazole-4-carboxylate and coupling to aldehyde V. First generation asymmetric routes to the C(1)-C(9) fragment centred on i. a biomimetic amino acid condensation route via an oxazoline intermediate based on the precedent of Meyers et al. and ii. a C(4)-C(5) disconnection approach based around the epoxide VII; are discussed in chapter 3. A second generation C(4)-C(5) disconnection centred on the novel tosylate VIII is discussed in chapter 4. Attempts to synthesise the parent C(1)- C(9) oxazole fragment using the tosylate VIII via i. a palladium catalysed C-H activation of ethyl 4-oxazole carboxylate and ii. lithiation of oxazole are reported. Coupling of fragment VIII (X = OTs) with ethyl 1H-pyrazole-4-carboxylate and a CuAAC coupling of the azide derived from tosylate VIII with methyl propiolate has allowed the successful completion of the synthesis of pyrazole and triazole analogues of this fragment

The new breed of business journalism for niche global news: The case of Bloomberg News

News providers such as Bloomberg’s multiplatform service and innumerable business-to-business magazines are flourishing despite the hugely challenging economic climate for journalism. They are catering for a new type of global audience that demands a different editorial strategy. Rather than writing news for local markets they produce for a global professional readership. This paper interrogates the nature of this global news style through linguistic analysis, supported by interviews with journalists. The paper raises questions about the continued efficacy of ‘‘traditional’’ models of journalism practice and notions of audience

Branding newspapers: visual texts as social practice

Since the turn of the century there has been a trend towards newspaper re-branding with increased attention to fonts, colours, layout and choices of images. Multimodal Critical Discourse Analysis (CDA) offers one useful tool for analysing the meaning potentials of these choices and the discourses that they realise. However, this paper, addressing one of the major criticisms of CDA, that it fails to consider the role of production factors in explaining textual choices, looks at these changes in the context of the re-branding of one newspaper. It shows how these must be understood as part of the more recent commercialisation of the news media, its alignment with marketing, and specifically with the market research profiling which lies behind the re-brand in this case. What we see are textual choices made in the context of news production aimed in the first place at consumers rather than citizens or readers. The paper demonstrates that failure to see the textual choices in the context of the social practice of news production would fail to provide any meaningful analysis

Synthesis of the C(1)-C(9) fragment of disorazole C1 and novel heterocyclic analogues

A highly convergent strategy for the synthesis of the antitubulin polyketide disorazole C1 is proposed based around the alkyne precursor I, featuring a novel Evans-Tishchenko/ring closing alkyne metathesis approach. Due to the inherent symmetry of the molecule this retrosynthesis leads to two fragments: a β- hydroxyketone II and the oxazole C(1)-(9) fragment III. A review of previous syntheses of disorazole C1 and established structure activity relationships (SARs) highlights a gap in current knowledge relating to the role of the oxazole in tubulin binding. Therefore, the focus of this research has been towards developing new routes for the synthesis of the C(1)-C(9) fragment that can be adapted to the synthesis of heterocyclic analogues to further establish the SAR of disorazole C1. Chapter 2 focuses on a disconnection at the C(5)-C(6) bond and a novel synthesis of the racemic C(1)-C(9) fragment has been achieved via a lithiation of methyl 2- methyl-1,3-oxazole-4-carboxylate and coupling to aldehyde V. First generation asymmetric routes to the C(1)-C(9) fragment centred on i. a biomimetic amino acid condensation route via an oxazoline intermediate based on the precedent of Meyers et al. and ii. a C(4)-C(5) disconnection approach based around the epoxide VII; are discussed in chapter 3. A second generation C(4)-C(5) disconnection centred on the novel tosylate VIII is discussed in chapter 4. Attempts to synthesise the parent C(1)- C(9) oxazole fragment using the tosylate VIII via i. a palladium catalysed C-H activation of ethyl 4-oxazole carboxylate and ii. lithiation of oxazole are reported. Coupling of fragment VIII (X = OTs) with ethyl 1H-pyrazole-4-carboxylate and a CuAAC coupling of the azide derived from tosylate VIII with methyl propiolate has allowed the successful completion of the synthesis of pyrazole and triazole analogues of this fragment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Reframing reporting of childhood sexual exploitation: three journalists reflect

This article explores three national and local journalists’ experiences of reporting on child sexual exploitation by so-called “Asian street grooming gangs” in UK towns and cities, with a particular emphasis on journalists framing journalists. In response to coverage of a series of cases, journalists have been accused by academics, policymakers and rival media organizations of fixating on perpetrators’ ethnicity and creating distorted, racist media frames. Few, if any, studies have garnered practitioners’ perspectives on how framing occurs, so we interview three prominent journalists who have covered such cases in order to deepen our understanding of the processes and causative factors behind particular editorial angles. While offering only a snapshot view, our findings reveal these individual journalists to be caught at the nexus of a range of factors that impact upon their work, both internally and externally driven

Feminist Visual Culture

From a primarily British perspective, this anthology comprises essays on feminist theory and the contribution of women artists to visual culture, while incorporating wider issues such as class, race, and ethnicity. Pajaczkowska provides a general introduction to the development of feminist practice within visual culture. Different aspects of feminist visual culture are divided into three sections: the fine arts, design, and the mass media. Each section is introduced by a text that raises the major issues and debates in that field. Biographical notes on the contributors. Index. List of illustrations. 295 bibl. ref