Lam, Hon Yiu. / "November 2011." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 122-135). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / Abstract (in Chinese) --- p.iv / Acknowledgement --- p.vi / Contents --- p.vii / List of Abbreviations --- p.xiii / List of Figures --- p.xiv / List of Tables --- p.xvii / Chapter 1 --- Literature review / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.2 --- Flavor of fish --- p.3 / Chapter 1.2.1 --- Carbonyls (aldehydes and ketones) and alcohols --- p.4 / Chapter 1.2.2 --- Sulfur-containing compounds --- p.5 / Chapter 1.2.3 --- Thermally-induced flavor --- p.5 / Chapter 1.2.4 --- Deteriorated fish flavor --- p.6 / Chapter 1.2.5 --- Autoxidation --- p.7 / Chapter 1.2.6 --- Bromophenols --- p.8 / Chapter 1.3 --- Bromophenols in aquaculture --- p.8 / Chapter 1.3.1 --- General properties of bromophenols --- p.9 / Chapter 1.3.2 --- Biosynthetic pathway of bromophenol in marine algae --- p.12 / Chapter 1.3.3 --- Thresholds of bromophenols --- p.14 / Chapter 1.3.4 --- Toxicity of bromophenols --- p.17 / Chapter 1.4 --- Giant Grouper --- p.19 / Chapter 1.4.1 --- Living Habitat of Giant Grouper --- p.19 / Chapter 1.4.2 --- Biological features of Giant Grouper --- p.23 / Chapter 1.4.3 --- Aquaculture of Giant Grouper --- p.23 / Chapter 1.5 --- Flavor analysis and extraction methods --- p.23 / Chapter 1.5.1 --- Solvent extraction --- p.25 / Chapter 1.5.2 --- Simultaneous Steam Distillation/Extraction --- p.25 / Chapter 1.5.3 --- Headspace sampling --- p.27 / Chapter 1.5.4 --- Gas Chromatography/Olfactometry (GCO) --- p.28 / Chapter 1.5.5 --- Food chemistry and Odor Threshold Value --- p.30 / Chapter 2 --- Distribution of bromophenols in selected Hong Kong dried seafood / Chapter 2.1 --- Introduction --- p.33 / Chapter 2.2 --- Materials and Methods --- p.34 / Chapter 2.2.1 --- Sample preparation --- p.34 / Chapter 2.2.2 --- "Preparation of the internal standard, Pentachloroanisole" --- p.35 / Chapter 2.2.3 --- Simultaneous steam distillation-solvent extraction (SDE) --- p.35 / Chapter 2.2.4 --- Gas chromatography-mass spectrometry (GC-MS) --- p.36 / Chapter 2.2.5 --- Compound identification --- p.37 / Chapter 2.2.6 --- Quantification of compounds --- p.37 / Chapter 2.2.7 --- Recovery --- p.37 / Chapter 2.2.8 --- Odor activity value (OAV) --- p.38 / Chapter 2.2.9 --- Statistical Analysis --- p.38 / Chapter 2.3 --- Results and discussion --- p.39 / Chapter 2.3.1 --- Distribution of bromophenols in dried seafoods --- p.39 / Chapter 2.3.2 --- Bromophenol contents in dried seaweeds --- p.51 / Chapter 2.3.3 --- Bromophenol contents in dried crustacean --- p.52 / Chapter 2.3.4 --- Bromophenol contents in dried mollusks --- p.53 / Chapter 2.3.5 --- Bromophenol contents in dried-salted fishes --- p.54 / Chapter 2.3.6 --- Relationship between living habitat and bromophenol contents --- p.55 / Chapter 2.3.7 --- Flavor impact of bromophenols in dried seafood --- p.57 / Chapter 2.3.8 --- Comparison of bromophenol content in purchased dried laminaria with Qingdao seaweed powder and bloodworms --- p.64 / Chapter 2.4 --- Conclusion --- p.67 / Chapter 3 --- Bromophenol content retention and fish quality in giant grouper / Chapter 3.1 --- Introduction --- p.70 / Chapter 3.2 --- Materials and Methods --- p.71 / Chapter 3.2.1 --- Abbreviation of treatment groups --- p.71 / Chapter 3.2.2 --- Sample preparation --- p.72 / Chapter 3.2.3 --- Ingredients --- p.72 / Chapter 3.2.4 --- Production of fish feed --- p.73 / Chapter 3.2.5 --- Preparation of the internal standard，Pentachloroanisole --- p.73 / Chapter 3.2.6 --- Simultaneous steam distillation-solvent extraction (SDE) --- p.75 / Chapter 3.2.7 --- Gas chromatography-mass spectrometry (GC-MS) --- p.75 / Chapter 3.2.8 --- Bromophenol identification and quantification --- p.76 / Chapter 3.2.9 --- Recovery of bromophenols --- p.76 / Chapter 3.2.10 --- Muscle color determination --- p.76 / Chapter 3.2.11 --- Texture analysis --- p.77 / Chapter 3.2.12 --- Moisture determination --- p.78 / Chapter 3.2.13 --- Ash determination --- p.78 / Chapter 3.2.14 --- Fat determination --- p.78 / Chapter 3.2.15 --- Protein determination --- p.79 / Chapter 3.2.16 --- Statistical Analysis --- p.80 / Chapter 3.3 --- Results and discussion --- p.80 / Chapter 3.3.1 --- Muscle color of giant grouper --- p.81 / Chapter 3.3.2 --- Texture of giant grouper --- p.85 / Chapter 3.3.3 --- Proximate analysis of giant grouper --- p.86 / Chapter 3.3.4 --- Bromophenol depuration of giant grouper --- p.92 / Chapter 3.4 --- Conclusion --- p.101 / Chapter 4 --- Volatile compounds in giant grouper / Chapter 4.1 --- Introduction --- p.102 / Chapter 4.2 --- Materials and Methods --- p.103 / Chapter 4.2.1 --- Sample preparation --- p.103 / Chapter 4.2.2 --- "Preparation of the internal standard, 2,4,6Trimethylpyridine (TMP)" --- p.104 / Chapter 4.2.3 --- Dynamic headspace (purge-and-trap) --- p.104 / Chapter 4.2.4 --- Simultaneous steam distillation-solvent extraction (SDE) --- p.105 / Chapter 4.2.5 --- Gas chromatography-mass spectrometry (GC-MS) --- p.105 / Chapter 4.2.6 --- Compound identification --- p.106 / Chapter 4.2.7 --- Quantification of compounds --- p.106 / Chapter 4.2.8 --- Recovery --- p.107 / Chapter 4.2.9 --- Odor activity value (OAV) --- p.108 / Chapter 4.2.10 --- Statistical analysis --- p.108 / Chapter 4.3 --- Results and discussion --- p.108 / Chapter 4.3.1 --- Comparison of extraction between dynamic headspace and SDE --- p.108 / Chapter 4.3.2 --- Flavor profile of giant grouper --- p.113 / Chapter 4.3.2.1 --- carbonyls and alcohol --- p.113 / Chapter 4.3.2.2 --- Other aroma volatile compounds in giant grouper --- p.116 / Chapter 4.3.3 --- Giant grouper tainted by water contamination --- p.116 / Chapter 4.4 --- Conclusion --- p.118 / Chapter 5 --- General conclusion --- p.119 / References --- p.122 / Appendix --- p.136

In this study, parameters for the adsorption of several halogenated phenolate ions to egg-phosphatidylcholine vesicles have been determined by microelectrophoresis.

La réaction de désaromatisation oxygénante de phénols est une transformation très utile en tant qu’étape clé dans la synthèse de substances naturelles complexes. Elle permet de préparer des intermédiaires de type cyclohexa-2,4-diénones à partir de phénols ortho-substitués, notamment en utilisant des réactifs iodés hypervalents (i.e., iodanes) qui constituent une alternative moderne aux réactifs à base de métaux lourds toxiques (e.g., Pb, Tl, Hg). Notre équipe s’intéresse plus particulièrement à la désaromatisation hydroxylante de 2-alkylphénols (réaction HPD) par des iodanes, transformation qui engendre la création d’un centre carboné quaternaire stéréogène. Le contrôle de la configuration de ce centre chiral par l’utilisation d’un substrat ou d’un réactif approprié est un de nos objectifs. Des iodanes chiraux récemment développés au laboratoire ont permis d’atteindre des excès énantiomériques de plus de 90% dans des réactions HPD modèles. Nous avons exploité avec succès ces iodanes chiraux pour réaliser les premières synthèses totales de la (–)-bacchopétiolone et de la (+)-mayténone, ainsi que pour élaborer la tête polaire de type ortho-quinol époxydé de la (+)-scyphostatine. / The oxygenative phenol dearomatization reaction is a very useful transformation, as a key step in the synthesis of complex natural substances. It gives access to cyclohexa-2,4-dienones from ortho-substituted phenols, through the use of hypervalent iodine reagents (i.e., iodanes), which constitutes a modern alternative to toxic heavy-metal-based reagents (e.g., Pb, Tl, Hg). Our team is interested in the hydroxylative dearomatization of 2-alkylphenols (HPD reaction) by iodanes, a transformation that results in the formation of one quaternary stereogenic center. Control of the absolute configuration of this chiral center through the use of an appropriate substrate or reagent is amongst our goals. Chiral iodanes recently developed in the laboratory allowed us to reach enantiomeric excesses above 90 % in model HPD reactions. Successful application of these chiral iodanes led us to achieve the first total syntheses of (–)-bacchopetiolone and (+)-maytenone, as well as that of the epoxy ortho- quinol polar head of (+)-scyphostatine.

Bibliography: leaves 87-96. This thesis investigates non-proteinaceous low molecular weight flavonoid and alkaloid compounds in Scurulla oortiana (Korth.) Danser grown on Camellia sinens. Three flavonols are identified in S. oortiana (Korth.) Danser growing on different hosts. The identification and characterisation of these flavonoids are carried out using various chromatographic and spectrometric procedures. Two purine alkaloids are isolated from and identified in S. oortiana (Korth.) Danser parasitizing tea plant, C. Sinensis. The antifungal activity of the phenolic compounds isolated from mistletoe parasitizing tea plant is examined.

Dietary antioxidants are believed to play an important role in the prevention and treatment of a variety of diseases associated with oxidative stress. Although there is a wide range of dietary antioxidants, the bulk of the research to date has been focused on the nutrient antioxidants vitamin C, E, and carotenoids. Certain relatively uncommon antioxidants such as lipoic acid (LA), and phenolic compounds such as (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), have not been extensively investigated although they may exert greater antioxidant potency than that of carotenoids and vitamins. Extracts from selected plants and plant byproducts may represent rich sources for one or more of such antioxidants and therefore exhibit higher effects than a single antioxidant due to the synergistic effects produced between such antioxidants. However, in the last decade a number of epidemiological, animal and in vitro studies have suggested a protective and therapeutic potency of these antioxidants in a broad range of diseases such as cancer, diabetes, atherosclerosis, cataract and acute and chronic neurological disorders. Inflammation, the response of the host toward any infection or injury, plays a central role in the development of many chronic diseases. Several evidences demonstrated the rise of different types of cancer from sites of inflammation. This suggests that active oxygen species and some cytokines generated in the inflamed tissues can cause injury to DNA and ultimately lead to carcinogenesis. Diethylnitrosamine (DEN) is one of the most important environmental carcinogens, present in a variety of foods, alcoholic beverages, tobacco smoke and it can be synthesized endogenously. In addition to the liver it can induce carcinogenesis in other organs like kidney, trachea, lung, esophagus, fore stomach, and nasal cavity. Several epidemiological and laboratory studies indicate that nitroso compounds including DEN may induce hyperplasia and chronic inflammation which is closely associated with the development of hepatocellular carcinoma. Despite increasing evidence on the potential of antioxidants in modulating the etiology of chronic diseases, little is known about their role in inflammation and acute phase response (APR). Therefore the aim of the present work was to study the protective effect of water and solvent extracts of eight plant and plant byproducts including green tea, artichoke, spinach, broccoli, onion and eggplant, orange and potato peels as well as eight antioxidants agents including EC, EGC, ECG, EGCG, ascorbic acid (AA), acetylcysteine (NAC), α-LA, and alpha-tocopherol (α-TOC) toward acute inflammation induced by interleukin-6 (IL-6) and hepatotoxicity induced by DEN in vitro. The negative acute phase proteins (APP), transthyretin (TTR) and retinol-binding protein (RBP) were used as inflammatory biomarkers analyzed by ELISA, whereas neutral red assay was used for evaluating the cytotoxicity. All experiments were performed in vitro using human hepatocarcinoma cell line (HepG2). Additionally the antioxidant activity was measured by TEAC and FRAP assays, phenolic content was measured by Folin–Ciocalteu and characterized by HPLC. Moreover, the microheterogeneity of TTR was detected using immunoprecipitation assay combined with SELDI-TOF MS. Results of present study showed that HepG2 cells provide a simple, sensitive in vitro system for studying the regulation of the negative APP, TTR and RBP under free and inflammatory condition. IL-6, a potent proinflammatory cytokine, in a concentration of 25 ng/ml was able to reduce TTR and RBP secretion by approximately 50-60% after 24h of incubation. With exception of broccoli and water extract of onion which showed pro-inflammatory effects in this study, all other plant extracts, at specific concentrations, were able to elevate TTR secretion in normal condition and even under treatment of IL-6 where the effect was quite lower. Green tea followed by artichoke and potato peel exhibited the highest elevation in TTR concentration which reached 1.1 and 2.5 folds of control in presence and absences of IL-6 respectively. In general Plant extracts were ordered according their anti-inflammatory potency as following: in water extracts; green tea > artichoke > potato peel > orange peel > spinach > eggplant peel, where in solvent extracts; green tea > artichoke > potato peel > spinach > eggplant peel > onion > orange peel. The antiinflammatory effect of water extracts of green tea, artichoke and orange peel were significantly higher than their corresponding solvent extracts whereas water extracts of eggplant-, potato peels and spinach showed lower effect than their solvent extracts. On the other hand α-LA followed by EGCG and ECG exhibited the highest elevation in TTR concentration compared to other antioxidants. The relation between the anti-inflammatory potential and antioxidants activity and phenolic content for the investigated substances was generally weak. This may suggest the involvement of other mechanisms than antioxidants properties for the observed effect. TTR secreted by HepG2 cells has a molecular structure quite similar to the purified standard and serum TTR in which all the three main variants are contained including native, S-cystinylated and Sglutathionylated TTR. Interestingly, a variant with molecular mass of 13453.8 + 8.3 Da has been detected only in TTR secreted by HepG2. Among all investigated antioxidants and plant extracts, six substances were able to elevate the native preferable TTR variant. The potency of these substances can be ordered as following α-LA > NAC > onion > AA > EGCG > green tea. A weak correlation between elevation on TTR and shifting to the native form was observed. Similar weak correlation has also been observed between antioxidants activity and elevation in native TTR. Although DEN was able to induce cell death in a concentration dependent manner, it requires considerably higher concentrations for its effects especially after 24h. This may be attributed to a lack in cytochrome P450 enzymes produced by HepG2. At selected concentrations some antioxidants and plant extracts significantly attenuate DEN cytotoxicity as following: spinach > α-LA > artichoke > orange peel > eggplant peel > α-TOC > onion > AA. Contrary all other substances especially green tea, broccoli, potato peel, and ECG stimulate DEN toxicity. In conclusion, this study demonstrated that selected antioxidants and plant extracts may attenuate the inflammatory process, not only by their antioxidants potency but also by other mechanisms which remain unclear. They may also play a vital role on stabilizing the tetramic structure of TTR and thereby prevent amyloidosis diseases. Lipoic acid represents in this study unique function against inflammation and hepatotoxicity. Despite the protective effect demonstrated by investigated substances, attention should also be given to the pro-oxidant and potential cytotoxic effects produced at higher concentrations. / Substanzen und Lebensmittelinhaltstoffe mit antioxidativer Wirkung spielen eine entscheidende Rolle in Prävention und Behandlung zahlreicher Erkrankungen, die mit oxidativen Stress assoziiert sind. Dabei stehen v. a. die Lebensmittelinhaltsstoffen Vitamin C (Ascorbinsäure, AA), Vitamin E und die Carotinoide im Zentrum der Forschung. Da einige bislang relativ ungebräuchliche Antioxidantien wie Liponsäure (LA) und phenolische Substanzen wie (-)-Epicatechin (EC), (-)-Epigallocatechin(EGC), (-)-Epicatechingallat (ECG), und (-)-Epigallocatechingallat (EGCG) ein größeres antioxidatives Potential als Carotinoide und die Vitamine C und E aufweisen, geraten diese in zunehmendem Maße in den Fokus der Forschung und wecken auch immer mehr das Interesse gesundheitsbewusster Verbraucher. Einige ausgewählte Pflanzenextrakte und Extrake pflanzlicher Nebenprodukte stellen ergiebige Quellen der oben erwähnten Substanzen dar und zeichnen sich daher durch eine höhere Wirksamkeit aus, die teilweise auch auf synergetische Effekte zwischen diesen Antioxidantien zurückzuführen ist. Eine Vielzahl epidemiologischer Studien sowie zahlreiche Tier- und in-vitro-Experimente deuten daher darauf hin, daß die oben erwähnten Antioxidantien bei einer Vielzahl von Erkrankugen, wie Krebs, Diabetes, Arteriosklerose, Katarakt, akute bzw. chronische neurologische Störungen, ein schützendes und therapeutisches Potential entfalten. Entzündungen, als Antwort eines Individuums auf Infektion oder Verletzungen, spielen eine zentrale Rolle bei der Entwicklung vieler chronischer Erkrankungen. So konnten mehrere Studien den Zusammenhang zwischen der Entstehung verschiedener Krebsarten und zugrundeliegender Infektionen belegen. Dies deutet darauf hin, dass reaktive Sauerstoffspezies und einige Zytokinen, die im entzündeten Geweben generiert werden und DNA-Schäden verursachen können, letztendlich auch eine Karzinogenese auslösen können. Diethylnitrosamin (DEN) ist eines der bekanntesten Umweltkarzinogene, daß neben Hepatokarzinomen auch Krebs in Nieren, Trachea, Lunge, Speiseröhre, Magen und Nasenhöhle hervorrufen kann und in vielen Lebensmitteln, alkoholischen Getränke sowie Tabakrauch enthalten ist und darüber hinaus endogen synthetisiert wird. Dabei geht man auf Grundlage mehrere epidemiologischer und Forschungsstudien davon aus, dass durch Nitroso-Verbindungen, u.a. auch DEN, induzierte Hyperplasien und chronische Entzündungen die Entwicklung hepatozellulärer Karzinome begünstigt. Trotz zunehmender Beweise bezüglich des Potentials von Antioxidantien die Ätiologie chronischer Erkrankungen zu modulieren, ist bislang nur sehr wenig über ihre Rolle im Entzündungsprozess und der Akutphasereaktion (APR) bekannt. Deshalb war das Ziel der vorliegenden Arbeit die schützende Wirkung von Extrakten verschiedener Pflanzen und Pflanzennebenprodukten sowie isolierten Antikoxidantien bei akuten Entzündungssituationen zu testen. Dazu wurden wässrige und Lösungsmittelextratke aus acht Pflanzen bzw. deren Nebenprodukten (Grüntee, Artischocke, Spinat, Brokkoli, Zwiebel, Aubergine-, Orangen- und Kartoffelschalen) hergestellt und ihre Wirkung sowie die acht weiterer reiner Antioxidantien (EC, EGC, ECG, EGCG, Ascorbinsäure (AA), Acetylcystein (NAC), LA, und -Tocopherol (TOC) in in-vitro-Modellen der akuten Entzündung, induziert durch interleukin-6 (IL-6), bzw. der Hepatoxizität, induziert durch DEN, getestet.. Transthyretin (TTR) und Retinol-Bindungsprotein (RBP), zwei negative Akutphasenproteine (APP) wurden als Entzündungsbiomarker (Analyse per ELISA) und Neutral-Red-Assay als ein Maß für die Cytotoxizität herangezogen. Alle Experimente wurden in-vitro in einer immortalisierten humanen Hepatokarzinom-Zelllinie (HepG2) durchgeführt. Die antioxidativen Kapazität wurde mittels TEAC und FRAP-Methoden evaluiert und der Gesamtphenolgehalt durch die Folin–Ciocalteu-Methode erfasst, wobei die qualitative Charakterisierung über die HPLC erfolgte. Die Mikroheterogenität des TTR wurde durch Immunopräzipitation in Kombination mit SELDI-TOF-MS Technik analysiert. Die Ergebnisse dieser Studie zeigen, dass HepG2-Zellen ein einfaches und empfindliches in-vitro System zur Regulierung von negativen Akutphasenproteinen, TTR und RBP, unter physiologischen und infllammatorischen Bedingungen darstellen. IL-6, ein potentes Pro-Entzündungszytokine, war bei einer 24stündigen Inkubation mit einer Konzentration von 25 ng/ ml in der Lage die Sekretion von TTR und RBP um ca. 50-60% zu reduzieren. Mit Ausnahme von Broccoli und Wasser Extrakt der Zwiebel, die zeigten, proinflammatorischen Effekt Wirkungen in dieser Studie, die alle anderen Pflanzenextrakten, in bestimmten Konzentrationen, waren in der Lage zu erheben TTR Sekretion im normalen, aber auch bei der Behandlung von IL-6 bei denen die Wirkung war niedriger. Grüntee, gefolgt von Artischocken und Kartoffelschälen zeigte die höchste Erhebung in der TTRKonzentration, die erreicht, 1,1 und 2,5 Falten der Kontrolle in Behandlung und ohne Behandlung von IL-6 bzw. Die wässrigen Pflanzenextrakte lassen sich in der folgenden Reihenfolge des anti-Entzündungspotentials einordnen: Grüntee > Artischocke > Kartoffelschalen > Orangenschalen > Spinat > Aubergineschalen, wogegen bei Lösungsmittelextrakte folgende Reihenfolge ermittelt wurde: Grüntee > Artischocke > Kartoffelnschalen > Spinat > Aubergineschalen > Zwiebel > Orangenschalen. Die schützende Wirkung der wässrigen Extrakte von Grüntee, Artischocke und Orangenschalen war signifikant höher als die der entsprechenden Lösungsmittelextrakte. Wohingegen wässrige Extrakte aus Aubergineschalen, Kartoffelschalen, Spinat und Zwiebel weniger effektiv waren. Auf der anderen Seite, LA gefolgt von EGCG und ECG zeigte die höchste Erhebung in der TTRKonzentration im Vergleich zu anderen Antioxidantien. Somit konnte ein schwacher aber Zusammenhang zwischen antinflammatorischem Potential, antioxidativer Aktivität und Phenolgehalt nachgewiesen werden. Daher ist anzunehmen, dass den beobachteten Effekten anderen Mechanismen zu Grunde liegen. Das durch HepG2-Zellen sezernierte TTR erwies eine molekulare Struktur ähnlich der des verwendeten Standards bzw. des TTR aus humanem Serum auf. Es enthielt alle drei Hauptvarianten, einschließlich der nativen, S-cystinylierten und S-glutathionylierten TTR-Formen. Darüber hinaus wurde nur im in-vitro sezerniertem TTR (TTR aus HepG2-Zellen) eine Variante mit einer molekularen Masse von 13453.8 + 8.3 Da nachgewiesen. Von den untersuchten Substanzen wiesen nur sechs Verbindungen die Fähigkeit auf den Anteil der günstigen nativen TTR-Form zu erhöhen aus. Dabei konnte folgende Wirksamkeitsreihenfolge zugeordnet werden : LA > NAC > Zwiebel > AA > EGCG > Grüntee. Eine schwache Korrelation zwischen der Erhöhung der TTRKonzentration und der Verschiebung zu der nativen Form hin wurde festgestellt. Ein ähnlicher Zusammenhang zwischen der antioxidativen Aktivität und dieser Erhöhung wurde auch beobachtet. Obwohl DEN in der Lage war konzentrationsabhängig den Zelltod zu induzieren, war eine wesentlich höhere Konzentration notwendig, um die volle Wirksamkeit während 24stündiger Inkubation zu gewährleisten. Dies mag auf die mangelnde Ausstattung mit Cytochrom-P450-Enzymen, die in den HepG2 Zellen produziert werden, zurück zu führen sein. Ausgewählte Konzentrationen einiger eingesetzter Substanzen führten zu einer signifikanten Schwächung der DEN-induzierten Zytotoxizität mit folgender Wirksamkeit: Spinat > LA > Artischocke > Orangen- > Aubergineschalen > TOC > Zwiebel > AA. Im Gegensatz dazu, stimulierten alle anderen Substanzen, insbesondere Grüntee, Brokkoli, Kartoffelschalen und ECG, die DEN –induzierten Toxizität. Diese Arbeit zeigt somit, dass ausgewählte Antioxidantien und Pflanzenextrakten in der Lage sind, den antinflammatorischen Prozess sowohl durch ihre antioxidative Wirkung als auch durch bislang nicht aufgeklärten Mechanismen grundlegend zu beeinflussen. Sie könnten daher eine entscheidende Rolle bei der Stabilisierung von Proteinstrukturen übernehmen (gezeigt am Beispiel vom TTR) und in diesem Zusammenhang möglicherweise auch zur Prävention von Krankheiten wie Amyloidosen beitragen. Liponsäure überzeugte in dieser Arbeit durch seine einzigartigen Funktion gegenüber Entzündungssituationen und Hepatoxizität. Wie oft beobachtet und durch diese Studie bestätigt, weisen die verwendeten Subsatzen neben der schützenden anti- auch pro-oxidativen Wirkungen auf, wodurch die Notwendigkeit weiterer Untersuchungen zur Erfassung der Zytotoxizität beim Einsatz höherer Konzentration verdeutlicht wird.

Phenol is highly reactive toward electrophilic aromatic substitution. By this general approach, many groups can be appended to the ring, via halogenation, acylation, sulfonation, and other processes. Phenol contains the hydroxyl group (–OH), which is a strongly activating ortho/para directing group in aromatic electrophilic substitution (AES). AES gives a mixture of ortho-and para isomers, which must be separated. The strong directing ability of phenol can also result in multiple substitutions on the aromatic ring which could be a major concern in the regiospecific synthesis of phenols. AES and Directed ortho--Metalation (DoM) are the only ways to directly substitute a proton on an aromatic ring and to synthesize regiospecifically substituted phenols. Phenol is a versatile precursor to a large collection of drugs, most notably aspirin, but also many herbicides and pharmaceuticals. AES reactions are useful in regiospecific synthesis as a way of introducing many reactive groups on the benzene ring and also help us to design a suitable method for synthesizing compounds in an efficient manner. Dimethylbenzylamine products are obtained as a result of the reaction of phenols with Eschenmoser’s salt (N,N-Dimethylmethyleneiminium iodide). This approach enables us to prepare regiospecifically ortho substituted phenols by using the AES protocol. We have discovered that Eschenmoser’s salt has the ability in basic medium containing triethylamine (TEA) to remove the proton and bond to the aromatic ring exclusively in ortho position to the –OH substituent. Our research work focused on efforts to render isolated products with minimum impurities, greener and more atom economical by use of limiting reagent in the reactions. For the purpose of evaluation of the obtained compounds and intermediates we use Gas Chromatography (GC), Gas Chromatography coupled with Mass Spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR). Our future work is to synthesize novel benzoheterocyclic compounds from the ortho-derivatised phenols as well as multi-substituted aromatic compounds. The dimethylamino methyl group can act as a directing group in the ortho-lithiation process; subsequent ortho--metalation and treatment with electrophiles generates 1,2,3- trisubstituted phenolic derivatives. Thus, phenolic precursors can be transformed into numerous derivatives which can be used in the chemical, agricultural and pharmaceutical industries.

The first part of this thesis describes the efficient synthesis of several hypervalent iodine(III) compounds. Electron-rich diaryliodonium salts have been synthesized in a one-pot procedure, employing mCPBA as the oxidant. Both symmetric and unsymmetric diaryliodonium tosylates can be isolated in high yields. An in situ anion exchange also enables the synthesis of previously unobtainable diaryliodonium triflates. A large-scale protocol for the synthesis of a derivative of Koser’s reagent, that is an isolable intermediate in the diaryliodonium tosylate synthesis, is furthermore described. The large-scale synthesis is performed in neat TFE, which can be recovered and recycled. This is very desirable from an environmental point of view. One of the few described syntheses of enantiopure diaryliodonium salts is discussed. Three different enantiopure diaryliodonium salts bearing electron-rich substituents are synthesized in moderate to high yields. The synthesis of these three salts shows the challenge in the preparation of electron-rich substituted unsymmetric salts. The second part of the thesis describes the application of both symmetric and unsymmetric diaryliodonium salts in organic synthesis. A metal-free efficient and fast method for the synthesis of diaryl ethers from diaryliodonium salts has been developed. The substrate scope is wide as both the phenol and the diaryliodonium salt can be varied. Products such as halogenated ethers, ortho-substituted ethers and bulky ethers, that are difficult to obtain with metal-catalyzed procedures, are readily prepared. The mild protocol allows arylation of racemization-prone a-amino acid derivatives without loss of enantiomeric excess. A chemoselectivity investigation was conducted, in which unsymmetric diaryliodonium salts were employed in the arylation of three different nucleophiles in order to understand the different factors that influence which aryl moiety that is transferred to the nucleophile. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted. Paper 5: Submitted. Paper 6: Manuscript.</p>

In Hinblick auf den stetig steigenden Bedarf der chemischen Industrie an Grundstoffchemikalien und der teilweise unsicheren Versorgung mit Erdöl und Erdgas ist es notwendig alternative Rohstoffe und Verwertungspfade für die Bereitstellung von Basischemikalien zu finden. Ziel der vorliegenden Arbeit war die Untersuchung der Hydrogenolyse von Lignin in niedermolekulare Produkte unter Verwendung geeigneter Salzschmelzen. Es konnte gezeigt werden, dass Lignin in Zinkchlorid/Kaliumchloridschmelzen in niedermolekulare Produkte abgebaut werden kann. Hierbei erwiesen sich der Einsatz eines entsprechenden Eutektikums und einer Alternativschmelze mit niedrigem Schmelzpunkt als hilfreich. Durch den Einsatz verschiedener Apparaturen wurden Untersuchungen in statischer und dynamischer Atmosphäre durchgeführt. Es ergaben sich während der Untersuchung Abhängigkeiten der Hydrogenolyse von verschiedenen Reaktionsparametern. Optima der Umsetzung hinsichtlich der Reaktionsparameter Temperatur, Zeit und Ligninanteil in der Schmelze wurden herausgearbeitet. Die Ausbeute an gewünschten Flüssigprodukten wurde, im Untersuchungsbereich, an diesen Punkten maximiert. Gleichzeitig war die Rückstands- und Gasbildung eingeschränkt. Es konnten Erkenntnisse eines komplexen Systems der Abhängigkeiten der Ausbeuten an Reaktionsprodukten von den Parametern der Untersuchung gewonnen werden. Die Hydrogenolyse von Lignin führte zur Aromatisierung fester Residuen sowie zur Abreicherung von Sauerstofffunktionalitäten. Komplexe Reaktionsmechanismen bewirkten den Abbau von Methoxyl-, Carboxyl- und Hydroxylgruppen der Ligninstruktur. Carbeniumionmechanismen konnten als wichtige Reaktionen zur Spaltung von Ether Arylbindungen identifiziert werden. Die Freisetzung von Monomeren und die Polymerisation anderer Intermediäre sind durch Sekundärreaktionen denkbar. Die gebildeten Flüssigprodukte bestanden hauptsächlich aus Monoaromaten (v.a. Guajakole und Kresole) und wenigen Polyaromaten. Die Selektivität der Bildung einzelner Verbindungen war gering, d.h. die Flüssigprodukte sind eine heterogene Mischung mit geringen Konzentrationen der Einzelsubstanzen. Die Unterschiede in der Struktur der Ausgangslignine bildeten sich auch in der Zusammensetzung der Flüssigprodukte ab. / In view of the steadily increasing demand of the chemical industry to base chemicals and the partial uncertain supply of crude oil and gas, it is necessary to find alternative raw materials and conversion routes for the provision of basic chemicals. The aim of the present work was to investigate the hydrogenolysis of lignin in low molecular weight products using appropriate molten salt media. It could be demonstrated that lignin can be convert in low molecular weight products using zinc chloride/potassium chloride molten salt media. The use of an appropriate eutectic melt and of an alternative melt with low melting point proved helpful. By the use of different apparatus investigations in static and dynamic atmosphere could be carried out. During the investigation dependencies of the hydrogenolysis of various reaction parameters are submitted. Optima of the hydrogenolysis regarding to reaction temperature, time and lignin content at the melt could be identified. The yields were maximized at these points in the range of investigation. Concurrently formation of gases and residues were suppressed. Some evidence of a complex system of the dependencies of the yields of reaction products are obtained from the parameters of the investigation. Hydrogenolysis of lignin leads to aromatic solid residues and to a loss of oxygen containing structures. Structures containing methoxyl-, carboxyl- and hydroxyl groups are degraded by various complex reaction mechanisms. Mechanisms of the formation of carbonium ions were identified as important reactions of the cleavage of ether aryl bonds. Secondary reactions caused the liberation of monomers and polymerisation of some intermediaries. The resulting liquid products consist mainly of monoaromatics (guaiacols and cresols) and less of polyaromatics. The selectivity of the formation of single compounds was low, i.e. the liquid products constitute a heterogenous mixture with low concentrations of the single compounds. The structural differencies of the feedstock lignins also showed at the composition of the liquid products.

No description available.

Polycyclic aromatic hydrocarbon (PAH) formation and growth from cyclopentadiene (CPD) moieties have been investigated using a laminar flow reactor and molecular modeling. The resonance-stabilized cyclopentadienyl radical is readily formed in flames and can participate in PAH growth to soot by reaction with the ??onds of aromatic species. Both CPD pyrolysis and computational results indicate that formation of indene and benzene is favored at low temperatures (below 750oC) and formation of naphthalene is favored at high temperatures. Reaction pathways from CPD have further been extended to PAH formation from the reaction of CPD and aromatic compounds with different types of ??onds. Results indicate that, while the major products from the pyrolysis of CPD, acenaphthylene, styrene and phenanthrene mixtures are from the reaction of CPD to itself rather than to these aromatic compounds with different ??onds, CPD does add to these compounds to produce larger PAH. Polychlorinated naphthalene (PCN) formation from chlorinated phenols has also been studied. In combustion exhaust gas, chlorinated phenols can produce dioxin as well as PCNs. PCN and polychlorinated dibenzofuran (PCDF) congener product distributions were consistent with proposed pathways involving phenoxy radical coupling at unchlorinated ortho-carbon sites. Tautomerization of the phenoxy radical coupling and subsequent fusion via H2O loss results in PCDF formation. Competing with this reaction pathway, CO elimination and subsequent fusion via hydrogen and/or chlorine loss was found to produce PCNs. PCDF isomer distributions were found to be weakly dependent to temperature, whereas PCN isomer distributions were found to be more temperature sensitive with selectivity to particular isomers decreasing with increasing temperature. Results of this research contribute to a better understanding of chemical mechanisms involved in the formation of toxic byproducts and soot in combustion systems.