Membrane technology has great potential to complement traditional energy-intensive molecular separation processes such as distillation, with the advantage of low footprint generation. However, this would only be achieved with the development of better membranes able to operate in challenging conditions, including combinations of organic solvents, high temperatures, extreme pHs, and oxidative environments. This dissertation aims to use high-performance polymeric materials that can withstand temperatures of 120 °C in polar aprotic solvents like N,N-dimethylformamide as separation membranes, using different crosslinking strategies and alternative routes for commercially available material processing. The thesis will be divided into two main approaches. The first approach will start from soluble polyimides as precursors, with designed functionalities that allow post-membrane modifications, such as chemical crosslinking, thermal crosslinking, and thermal rearrangement to enhance the material's chemical resistance. The focus will be on the polyimide synthesis by an alternative one-step room-temperature polyhydroxyalkylation reaction. The chemical and thermal crosslinking take place without involving the imide bond, by incorporating a highly tunable functional group (isatin) in the synthesis of the materials. Propargyl as a pendant group will be used for the thermal crosslinking, and hydroxyl group for the thermal rearrangement. In all cases, the obtained membranes were stable in common organic solvents at 120 °C. The second approach will start from intrinsically solvent-resistant and commercially available poly(aryl ether ketone)s, turned into membranes by a closed-loop modification-regeneration strategy, to address long-term separations in organic solvents at high temperatures. We present for the first time porous poly(aryl ether ketone) flat-sheet and hollow fiber membranes prepared without the use of strong acids or high temperatures. Two methodologies are proposed. The developed strategies shall contribute toward avoiding the regular consumption of new materials and waste generation since the polymer used does not require crosslinking for its stability under organic solvents.

Ketosis is a metabolic condition that occurs during heat stress, prolonged exercise, fasting, and in obese and diabetic individuals. The major ketone body, β-OH butyrate, affects cellular signaling pathways in a hormone-like manner through its receptor GPR109a. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of diabetes. To understand how β-OH butyrate signaling affects hepatic metabolism we compared the fasting response in control and 3-hydroxy-3-methylglutaryl-CoA Synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production, and in GPR109a +/+ and -/- mice. To directly assess the response to ketone signaling we gave intraperitoneal injections of the GPR109a agonists niacin (0.8mmol/kg) and β-OH butyrate (5.7mmol/kg) to HMGCS2 knockdown mice over the final 9 hours of a 16 hour fast. Ketogenic deficient mice showed a more robust increase in hepatic carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 2 (UCP2) mRNA than control mice in response to fasting. Accordingly, niacin and β-OH butyrate administration decreased fasting CPT1 mRNA expression in knockdown mice, while fasting knockdown UCP2 mRNA and control HMGCS2 mRNA were lowered by β-OH butyrate. GPR109a knockout did not alter the hepatic response to fasting, although the effect of niacin on fasting HMGCS2 mRNA expression was dependent on GPR109a expression. While the role of GPR109a and how chronic hyperketonemia alters β-OH butyrate signaling require further study, these data suggest that endogenous β-OH butyrate signaling during a fast regulates the transcript levels of hepatic genes directly involved in its own synthesis.

This work is an in-depth study of a system with an approach designed to determine the electrode processes and the factors or conditions which control them.

Benzoin is an important a-hydroxy ketone which can be used as chiral intermediate for the synthesis of several drugs. In this study, it was aimed to synthesize this compound by high stereoslectivity and yield by the use of fungal bioconversions. For this purpose, whole cells of four different Fusarium spp. (F. anguoides, F. roseum, F. solanii, F.bulbigenum) were used for reduction of readily available achiral compound benzil. The reaction conditions were optimized as glucose peptone broth consisting of 30g/L glucose and 10 g/L peptone, inoculum size as 20 mg/L and substrate concentration as 200 mg/L. A complete set of derivatives substituted with electron donating and electron withdrawing groups of the benzils were also reduced to the corresponding benzoin derivatives with the same optimized condition with up to 98% ee.

The research presented herein explores three aspects of asymmetric catalysis: (1) the development of new catalytic enantioselective reactions, (2) the application of stereoselective catalysis to natural product total synthesis, and (3) the design and synthesis of new chiral catalysts. / Chemistry and Chemical Biology

Diacetyl (2,3-butanedione) is an important flavour active, oxidative compound that has significant impact on cellular health as well as financial impact in industrial fermentations. The presence of diacetyl in certain fermented beverages, such as beer, results in an unpleasant butterscotch-like flavour and its concentration needs to be reduced by yeast to below the taste threshold prior to filtration and packaging. This results in significant process inefficiency. Furthermore, diacetyl negatively impacts cellular health and has been associated with neurodegenerative diseases and general cell aging amongst others. The reduction of this compound is therefore essential for cellular health. / Several yeast cell enzymatic mechanisms responsible for diacetyl reduction were identified and characterised, including Old Yellow Enzyme (OYE) isoforms and D-Arabinose Dehydrogenase (ARA1). OYE isoforms displayed different micromolar affinities and catalytic turnover rates for diacetyl and catalysed diacetyl reduction in a biphasic manner. ARA1 catalysed diacetyl reduction in a monophasic manner with a millimolar Michaelis constant. / Knowledge gained in these studies was applied in investigations of diacetyl production and reduction in industrial brewing operations and the enzymatic systems further exploited for the development of a novel enzyme based assay to determine diacetyl concentrations in beer samples. Concentrations as low as 0.2 muM were detectable with high repeatability.

Thesis (M.A.)--Mahidol University, 1982.

Doctor of Philosophy / Department of Chemical Engineering / Keith L. Hohn / The present work describes the conversion of bio-derived methyl ethyl ketone (MEK) into different useful chemicals. The first part discusses the direct conversion of MEK to butene over supported copper catalysts (Cu-Al₂O₃, Cu-zeolite Y sodium (Cu-ZYNa) and Cu-zeolite Y hydrogen (Cu-ZYH)) in a fixed bed reactor. In this reaction, MEK is hydrogenated to 2-butanol over metal sites, and further dehydrated on acid sites to produce butene. Experimental results showed that the selectivity of butene was the highest over Cu-ZYNa, and it was improved by finding the optimum reaction temperature, hydrogen pressure and the percentage of copper loaded on ZYNa. The highest selectivity of butene (97.9%) was obtained at 270 °C and 20 wt% Cu-ZYNa. Over Cu-Al₂O₃, the selectivity of butenes was less than Cu-ZYNa since subsequent hydrogenation of butene occurred to produce butane. It was also observed that with increasing H₂/MEK molar ratio, butane selectivity increased. However, when this ratio was decreased, hydrogenation of butene was reduced, but dimerization to C₈ alkenes and alkane began to be favored. The main products over 20% Cu-Al₂O₃ were butene and butane, and the maximum selectivity of butene (87%) was achieved at an H₂/MEK molar ratio of five. The lowest selectivity of butene was obtained using Cu-ZYH, reaching ~40%. It was found that the amount of acidity in Cu-ZYH is much higher than in Cu-ZYNa (from (NH₃-TPD) measurements). This could have caused the selectivity of butene to decrease as a result of dimerization, oligomerization and cracking reactions. The second part describes the conversion of MEK to higher ketones in one step using a multifunctional catalyst having both aldol condensation (aldolization and dehydration) and hydrogenation properties. 15% Cu supported zirconia (ZrO₂) was investigated in the catalytic gas phase reaction of MEK in a fixed bed reactor. The results showed that the main product was 5-methyl-3-heptanone in addition to 5-methyl-3-heptanol and 2-butanol with side products including other heavy products (C₁₂ and up). The effects of temperature and the molar ratio of reactants (H₂/MEK) on overall product selectivity were studied. It was found that with increasing temperature, the selectivity to C₈ ketone increased, while selectivity to 2-butanol decreased. The hydrogen pressure plays significant role on the selectivity of products. It was observed that with increasing the H₂/MEK molar ratio, 2-butanol selectivity increased due to hydrogenation reaction while decreasing this ratio leads to increasing aldol condensation products. In addition, it was noted that both conversion and selectivity to the main product increased using a low loading percentage of copper, 1% Cu-ZrO₂. The highest selectivity of 5-methyl-3-heptanone (~63%) was obtained at temperatures around 180 °C and a molar ratio of H₂/MEK of 2. Other metals (Ni, Pd and Pt) supported on ZrO₂ also produced 5-methyl 3-heptanone as the main product with slight differences in selectivity, suggesting that a hydrogenation catalyst is important for making the C₈ ketone, but the exact identity of the metal is less important. The third part discusses the conversion of C₈ ketones to C₈ alkenes and C₈ alkane over a catalyst consisting of a transition metal (Cu or Pt) loaded on alumina (Al₂O₃). These bifunctional catalysts provide both hydrogenation and dehydration functionalities. The main products over 20% Cu-Al₂O₃ were a mixture of 5-methyl-3-heptene, 5-methyl-2-heptene and 3-methyl heptane. However, using 1% Pt-Al₂O₃ the major product was 3-methyl heptane with a selectivity reaching over 97% and a conversion of 99.9 %. Both temperature and the hydrogen pressure play an important role on the conversion of C₈ ketone as well as the selectivity of products (C₈ alkenes and C₈ alkane). Over 20% Cu-Al₂O₃, it was observed that increasing the reaction temperature led to an increase in the selectivity to C₈ alkane as a result of hydrogenation of the C₈ alkene. Also, it was observed that with an increase in H₂/C₈ ketone molar ratio, C₈ alkane selectivity increased. However, when this ratio was decreased, the further hydrogenation of C₈ alkene to C₈ alkane was reduced. The highest selectivity of C₈ alkene (81.7%) was obtained at 220 °C and a H₂/C₈ ketone molar ratio of 2. In addition, an experiment was carried out using a low loading percentage of copper, and it was noted that both conversion and selectivity to the main products decreased over 1% Cu-Al₂O₃. Over 1% Pt-Al₂O₃, C₈ alkane was the major product with different temperatures indicating that further hydrogenation of C₈ alkene was promoted on 1% Pt-Al₂O₃. At low temperature, for both Cu-Al₂O₃ and Pt-Al₂O₃, significant amounts of C₈ alcohols are formed because subsequent reactions do not proceed at a fast enough rate. Also using 1% Pt-Al₂O₃, the main product selectivity is still C₈ alkane with all H₂/C₈ ketone ratios.

Andrographis paniculata est une échinacée d’origine asiatique utilisée depuis plus de deux milles ans en médecine traditionnelle asiatique. Ses activités anti-bactériennes, anti-virales et hépatoprotectrices, entre autre, en ont fait un sujet d’étude important depuis les trente dernières années. Cette plante est principalement constituée de diterpènes de série ent-labdanes, dont le composé majoritaire est l’andrographolide, une lactone diterpénique, qui a montré des propriétés anti-inflammatoires sur la voie NFB. C’est dans le but de comprendre et d’améliorer les activités anti-inflammatoires des composés issus de la plante que nous avons envisagé l’étude de la famille des andrographolides. Une étude qualitative d’extraits issus de compléments alimentaires a permis d’obtenir trois composés naturels, qui ont été pharmacomodulés chimiquement. De plus, une méthode quantitative de quatre extraits bruts a permis de déterminer la concentration des trois composés naturels isolés dans chaque mélange. Les composés isolés, ceux modifés par hémisynthèse, ainsi que les mélanges de composition déterminée ont fait l’objet de tests d’activité anti-inflammatoire. Afin de modifier la structure de l’andrographolide sur des positions non accessibles par hémisynthèse, la synthèse totale et énantiosélective du produit naturel a été envisagée. Deux voies de synthèses ont été envisagées pour la préparation de ce composé : une voie biomimétique et une voie utilisant la cétone de Wieland-Miescher. Cette dernière voie est divisée en trois parties (cyclisation énantiosélective, fonctionnalisation du cycle A, fonctionnalisation du cycle B). Ainsi, nous avons pu mettre au point des méthodologies permettant de fonctionnaliser chaque cycle et d’accéder à la synthèse d’analogues de l’andrographolide. / Andrographis paniculata is an Asian Echinacea. This plant is widely used in traditionnal remedies and folkloric medicines for thousands years and is reported to possess a wide spectrum of biological activities. A large number of diterpenoid ent-labdanes have been isolated from this plant, where the major compound is andrographolide, a diterpenoid lactone, that exhibits interesting anti-inflammatory activities on the NFB way. In order to understand and improve the anti-inflammatory activity of these compounds, we implemented a program aimed at their study. Qualitative analysis of crude extracts from dietary supplements allowed to obtain three major natural compounds, which were in a second time chemically modified. These products, as well as the crude extracts, where the composition was determined by a quantitative method, were used for the study of anti-inflammatory activity. Our aim was also to modify andrographolide on some positions not accessible by hemisynthesis. So total and enantioselective synthesis of andrographolide was investigated. Two ways were studied: biomimetic pathway, and modification of a bicyclic precursor that already possessed the ent-labdane configuration (Wieland-Miescher ketone). Methodology using Wieland-Miescher ketone was divided in three parts (enantioselective cyclisation, cycle A functionalisation, cycle B functionalisation). By this way, the bicyclic core was successfully functionnalised and analogues of andrographolide were prepared.

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