Cheuk Lai-Yee. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 153-184). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Lee Tin Lap. / "January 2001." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 161-185). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Tetramethyldihydroxanthenes constitute a large class of natural products wherein a 6-member ring triketone moiety is linked to an aromatic moiety. Progress toward the syntheses of six biologically active natural products isolated from these genus species; rhodomyrtone A, rhodomyrtosones A and B, tomentosones A and B, and bullataketals A and B, are described. These compounds possess challenging structures and interesting bioactivities making them attractive targets. Isolation, structure elucidation and biosyntheses of rhodomyrtone A, rhodomyrtosone A and B, tomentosones A and B, and bullataketals A and B are discussed. To accomplish their total syntheses, several new methodologies have been developed. A nickel-mediated catalytic 1,4-conjugate addition was developed. Literature precedents showcasing the use of nickel-mediated 1,4-conjugate addition and previously reported nickel-mediated enantioselective catalytic systems are presented herein along with our work. The challenges met during the development of a regioselective dehydrative cyclization for the syntheses of rhodomyrtone A and rhodomyrtosone B are discussed and strategies designed to overcome this synthetic challenge are presented in detail. Our studies to develop a flow photochemistry-mediated process to access endoperoxides, as well as generation and trapping of active vinyloxocarbenium intermediates are presented along with relevant literature precedents.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

La découverte de l'Artémisinine, un 1,2,4-trioxacyclohexane, et le fait que la liaison endoperoxide est essentielle pour son activité antimalarique, a conduit les chimistes à la synthèse de nouvelles molécules contenant le motif endoperoxide pour obtenir de nouveaux leaders. Certains de ces composés peroxidiques sont les 1,2-dioxanes et les 1,2,4,5-tetraoxanes. À cet égard, la première partie de mon travail a été réalisée dans le laboratoire du professeur Giuseppe Campiani à l'université de Sienne et a inclus la synthèse d'analogues 1,2-dioxane du produit naturel Plakortine mais aussi le développement d'une stratégie de synthèse polyvalent du produit naturel 9,10-dihydroplakortine. Une des étapes clés dans notre approche synthétique a été la stéréosélectivité des réactions ainsi que la formation du squelette chiral 1,2-dioxane. En combinant l'époxidation dissymétrique de Sharpless à l'hydroperoxysilylation régiosélective d'alcène catalysée par le cobalt (II) de Mukaiyama-Isayama, la stéréochimie désirée a été obtenue. Dans la seconde partie de mon doctorat qui a pris place dans le laboratoire du professeur Paul O'Neill à l'université de Liverpool, la conception, la synthèse et l'évaluation du potentiel antimalarique de deux nouvelles séries de 1,2,4,5-tetraoxanes ont été réalisées. La première série de tetraoxanes, appelée les Mannoxanes, est une drogue hybride qui possède un noyau tetraoxane et une chaine latérale basique insérée grâce à une réaction de mannich. La seconde série a été préparée par une approche utilisant l'amination réductrice pour inclure la chaine latérale basique sur le noyau tetraoxane. Les deux séries ont montré d'excellentes activités antimalariques (de l'ordre du nanomolaire) contre plasmodium falciparum. / The discovery of artemisinin, a 1,2,4-trioxacyclohexane, and the fact that the endoperoxide bond is essential for its antimalarial activity has led chemists to synthesize new molecules containing the endoperoxide moiety in order to find new antimalarial hits. Some of these peroxidic compounds include the 1,2-dioxanes and the 1,2,4,5-tetraoxanes. In this regard, work on the first part of the PhD (Chapter 2) has been developed in the laboratories of Prof. Giuseppe Campiani at the University of Siena and includes the synthesis of 1,2-dioxane analogues of natural product Plakortin and the development of a versatile synthetic strategy to the natural compound 9,10-dihydroplakortin. One of the key issues in our synthetic approach has been the stereoselectivity of the reactions and the formation of the chiral 1,2-dioxane skeleton. By combining Sharpless asymmetric epoxidation to the Mukaiyama-Isayama Co(II)-catalyzed regioselective hydroperoxysilylation of an alkene, the desired stereochemistry has been obtained. In the second part of the PhD (Chapter 3), which has taken place in the laboratories of Prof. Paul O'Neill at the University of Liverpool, design, synthesis and assessment of the antimalarial potency of two new series of 1,2,4,5-tetraoxanes has been achieved. The first series of novel tetraoxanes are called Mannoxanes and are hybrid drugs that include a tetraoxane and a mannich basic phenol side-chain. The second new series has been synthesized by using a reductive amination approach to include the basic side chain in the tetraoxane molecule scaffold. Both of these series have shown excellent antimalarial activities against Plasmodium falciparum in the low nanomolar range.

by Wai-keung Leung. / Thesis (M.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 217-232). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Cheng Sze-Lok Alfred. / "March 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 175-211). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Dietary fish oil supplementation has long been shown to have significant health benefits, largely stemming from the anti-inflammatory activity of the ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) present in fish oils. The anti-inflammatory properties of these fatty acids has been linked to beneficial health effects, such as protecting the heart, in individuals consuming diets rich in fish, or supplemented with fish oils. These effects are highly notable in the Māori people native to coastal regions of New Zealand; the significantly lower rates of heart problems compared to the inland populous has been attributed to the consumption of the green lipped mussel Perna Canaliculus. Commercially available health supplements based on the New Zealand green lipped mussel include a freeze-dried powder and a lipid extract (Lyprinol®), the latter of which has shown anti-inflammatory properties comparable to classical non-steroidal anti-inflammatory drugs (NSAIDs) such as Naproxen. GCMS analysis of Lyprinol by Murphy et al. showed the presence of a class of ω-4 and ω-6 PUFAs bearing a highly electron rich tri- or tetra-alkyl furan ring, which were designated furan fatty acids (F-acids). Due to their instability, isolation of F-acids from natural sources cannot be carried out and a general synthetic route toward this class of natural products was required. To accomplish this, the biosynthesis of F-acids was mimicked by utilising an oxidation of 1,3-dienes, followed by a dehydration/aromatisation to generate the heterocyclic furan ring. Singlet oxygen was chosen as the means of oxidising the conjugated dienes giving endoperoxides. To mimic the biological aromatisation of the peroxide intermediates the Appel reagent was chosen and, in a novel application of the reagent, was exploited as a mild, metal free method of dehydrating the cyclic peroxides to their corresponding furans. The biomimetic furan synthesis was applied toward a selection of 1,3-diene substrates bearing a range of pre-installed functionalities and substitution patterns including alkyl, aryl, alkenes, cyclopropyl rings, silyl ethers, and esters, alongside being applied to the total synthesis of the furan fatty acid F5. A brief exploration of the possibility of performing the aromatisation reaction under catalytic conditions was carried out, to determine whether endoperoxides could be converted to furans without needing a stoichiometric quantity of Appel reagent, by harnessing a catalytic quantity of triphenylphosphine oxide and regenerating the active P(V) species via reaction with oxalyl chloride. Furthermore, an optimisation study was carried out using a simple design of experiments procedure to ascertain the ideal conditions for carrying out the Appel-type dehydration of endoperoxides. Finally, the scope of the reaction sequence was expanded to be performed in a continuous flow reactor, with telescoping of the singlet oxygen diene oxidation and Appel-type aromatisation to increase oxidation yields and to omit the requirement for isolation of peroxide intermediates, and was applied to the synthesis of a selection of 2,5-diaryl furan motifs.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.