A variety of heterocyclic alcohols were coupled with silyl ketene acetals and other [pi]-nucleophiles in the presence of trimethylsilyl trifluoromethanesulfonate to provide an array of substituted [beta]-heteroaryl propionates, including those with contiguous quaternary centers. This reaction also proceeds with high diastereoselectivity when the [pi]-nucleophile bears a chiral auxiliary. The formal synthesis of N-methylwelwitindolinone C isothiocyanate, a densely functionalized alkaloid with the ability to reverse multiple drug resistance, was completed featuring several key transformations. The first key transformation consisted of coupling a heterocyclic alcohol with a silyl ketene acetal to give a highly functionalized intermediate. Next, a palladium catalyzed enolate arylation followed by an intramolecular allylic alkylation successfully constructed the bicyclo(4.3.1)decane backbone of the N-methylwelwitindolinone C isothiocyanate. / text

Herbivores have a significant role in tundra ecosystem composition and processes. They can cause changes of vegetation composition and nutrient content that result in altered palatability of the vegetation and food availability for herbivores. The direct effect of herbivores on plant quality and quantity have been studied in detail, and recent studies have shown that present vegetation composition and soil processes might show legacies of historical grazing a century ago. This raises the question if historical grazing also has a legacy on the palatability of the vegetation. In this study, I investigated if the quality of the vegetation of the Historical Milking Grounds (HMGs) heavily grazed up until a century ago is still under influence a century after the heavy grazing has ceased. I focused on the nitrogen content and digestibility of the vegetation, since these should be two independent measures of food quality which, when evaluated together, should give a good estimate of the quality of the forage.

The composition of sludge organic matter is mainly influenced by the origin of wastewater. The biochemical composition of sludge could, however, alter from post wastewater treatment drying techniques. Such changes have a direct effect on the N fertilizer value of sludge because the biochemical composition of sludge dictates its decomposition rate. Therefore, proper understanding of the effect of wastewater treatment methods and post treatment drying techniques on a) the C and N contents as well as organic matter composition of sludge, and b) C decomposition and N mineralization is crucial for N management in sludge amended agricultural lands. The aim of this study was to investigate the effect of selected wastewater treatment and post treatment drying techniques on a) the N, C, and organic matter composition, as well as b) C decomposition and N mineralization of municipal sewage sludge. The study also investigated the compounds responsible for C and N release during a decomposition process. Two consecutive incubation studies (100 days each) were conducted to determine N release, C decomposition and sludge organic matter decomposition using different sludge types namely: Thermally hydrolysed sludge (THS), Activated sludge (Activated), and anaerobically digested sludge. The anaerobically digested sludges were collected from two different drying techniques (concrete beds and earth paddy) as well as two sludge drying depths on beds ( 10 cm and 25 cm). Inorganic N was determined by the steam distillation method. Sludge organic matter composition was analysed using Van Soest method. Total N and total organic C were determined using Carlo-Erba method. A parallel sludge alone incubation study was conducted from which organic compounds degradation and transformation analysis were conducted. The anaerobically digested sludge dried in thin layers of 10 cm (ADS3) had higher total N (4.95%) than similar sludge types dried in thick layers of 25 cm in concrete beds (ADS1= 2.81%N) and in earth paddy (ADS2 = 2.83%N). Large fraction (>60%) of the organic C in all sludge types was in soluble compounds form (SOL). Thermally hydrolyzed sludge (THS) had the highest (90%) SOL. ADS3 and Activated had lower lignin fraction (<3%) than THS, ADS1 and ADS2. Net N mineralization per kg C applied was highest for activated (77 g kg-1 C) and was lowest for ADS2 (23 g kg-1 C). Despite having highest SOL, THS had relatively lower net N mineralization per kg organic N applied (350 g kg-1 organic N) than Activated sludge (449 g kg-1 organic N) mainly due to the relatively higher lignin fraction. It was apparent from this study that the soluble compounds were responsible for about 90% of the organic matter decomposition. The Van Soest method was also successfully used to determine residual compounds at intervals during the incubation study from the sludge alone study but not with the soilsludge mixture. / Dissertation (MSc)--University of Pretoria, 2014. / National Research Foundation (NRF) Water Research Commission (WRC), East Rand Water Care Company (ERWAT) / Plant Production and Soil Science / MSc / Unrestricted

Chapter 2 of the thesis describes a highly efficient in situ method for the reduction of amides to aldehydes and aryl O-carbamates to phenols and other transformations involving hydrozirconations. The method, as a three-component-type reaction, involves in situ generation of the Schwartz reagent (Cp2Zr(H)Cl) from Cp2ZrCl2 and the reductant, LiAlH(O-t-Bu)3, and immediate reaction with a substrate. Substrates include aliphatic and aromatic tertiary amides which are reduced to aldehydes, aryl O-carbamates which are reduced to phenols, and alkynes which undergo other transformations via hydrozirconation. Compared to prior methods, this method has advantage in that reagents are inexpensive and stable, reaction times are short, and reaction temperatures are generally conveniently at room temperature. The use of the in situ method described herein instead of the requirement for the synthesis of the commercially available Schwartz reagent is estimated to provide more than 50% reduction in cost. Chapter 3 of the thesis describes the discovery and development of efficient and regioselective Ru-catalyzed amide-directed C-H, C-N, C-O activation/C-C bond forming reactions, ester-directed C-O activation/C-C bond forming reaction, and amide-directed C-O activation/hydrodemethoxylation reactions under a simple RuH2(CO)(PPh3)3/toluene catalytic system. Of these, the amide-directed C-H activation/cross coupling reaction proceeds well but uniquely on furan 3-amide substrates while the ester-directed C-O activation is effective on the 2-MeO-1-naphthoic acid methyl ester. On the other hand, the amide-directed C-N and C-O activation/coupling reactions are broadly applicable on benzamides and naphthamides. All of these achievements of directed C-H, C-N, C-O activation/coupling reactions complement and may supercede the DoM (directed ortho metalation)-cross coupling strategy, and establish the catalytic base-free DoM-cross coupling process at non-cryogenic temperature as a convenient, economical and green alternative. The new catalytic amide-directed ortho-hydrodemethoxylation reaction has potential value in links to aromatic electrophilic substitution and DoM chemistries. Furthermore, a new borylation reaction via Ru-catalyzed amide-directed C-H activation/C-B bond forming process is also reported herein. / Thesis (Ph.D, Chemistry) -- Queen's University, 2010-12-21 11:12:35.564

<p> The nitrogen and hydrogen-deuterium isotope effects have been measured for the base-promoted elimination reactions of cis-and trans-2-phenylcyclopentyltrimethylammonium ions and cis-and trans-2-phenylcyclohexyltrimethylammonium ions. The observations have been interpr eted as indicative of a concerted E2 mechanism for both trans and cis elimination processes. In the cis eliminations, however, proton transfer to base is far advanced at the transition state resulting in a much higher degree of carbanionic character ass ociated with the transition state than for the trans eliminations. </p> <p> The kinetic isotope effect results for these cyclic systems establish that the two bond-rupture processes complement each other; the greater the extent of proton transfer to base at the transition state, the smaller is the extent of C-N bond weakening. These observations are interpreted in terms of the coupling of the motion which extends the lengths of the H-C and C-N bonds at the transition state and the approach to coplanarity of the bonds involved in the elimination process. </p> / Thesis / Doctor of Philosophy (PhD)

The Dong research group is interested in harnessing the power of transition metal catalysis to transform simple molecules and reagents (such as carbon monoxide, hydrogen gas, olefins, and C–H and C–O bonds) into valuable products (such as functionalized heterocycles, chiral carbonyl compounds and natural products). This thesis will describe our continual effort to achieve this goal. Part I describes the Pd-catalyzed functionalization of sp2 and sp3 C–H bonds. Carbon monoxide is used as a stoichiometric reductant in the cyclization of diarylnitroalkenes to afford biologically relevant 3-arylindoles and other N-containing heterocycles with carbon dioxide as the only stoichiometric byproduct. Also, an aryl sulfoxide moiety is shown to direct the arylation of sp3 C–H bonds to afford beta-functionalized amides. Part II describes the Ru-catalyzed sp3 C–O bond activation of alkoxypyridines and related heterocycles. In this transformation, an O- to N-alkyl migratory rearrangement occurs to afford N-alkylated pyridones which are structures found in many natural products and pharmaceutical agents. Part III describes our pursuit of metal-catalyzed asymmetric synthesis. Readily available benzylic bromides are carbonylated with carbon monoxide in alcoholic solvent mixtures. The resulting medicinally relevant 2-arylpropionic esters are obtained with moderate to good enantioselectivities. Preliminary results for the asymmetric hydrogenation of gem-diarylethylenes and novel ligand development are also disclosed. Part IV describes our efforts towards the total synthesis of 6-deoxyerythronolide B. Our retrosynthetic analysis of the macrolide antibiotic involves disconnections at the lactone linkage and between C7 and C8. The two equally complex fragments were prepared via reliable aldol, hydroboration, crotylation and redox chemistry. Rather than the typical macrolactonization method to form the 14-membered ring, we propose an alternative strategy where we plan to cyclize with a metal-catalyzed ring-closing metathesis event. Currently, this step is under investigation by other members in the group.

The Dong research group is interested in harnessing the power of transition metal catalysis to transform simple molecules and reagents (such as carbon monoxide, hydrogen gas, olefins, and C–H and C–O bonds) into valuable products (such as functionalized heterocycles, chiral carbonyl compounds and natural products). This thesis will describe our continual effort to achieve this goal. Part I describes the Pd-catalyzed functionalization of sp2 and sp3 C–H bonds. Carbon monoxide is used as a stoichiometric reductant in the cyclization of diarylnitroalkenes to afford biologically relevant 3-arylindoles and other N-containing heterocycles with carbon dioxide as the only stoichiometric byproduct. Also, an aryl sulfoxide moiety is shown to direct the arylation of sp3 C–H bonds to afford beta-functionalized amides. Part II describes the Ru-catalyzed sp3 C–O bond activation of alkoxypyridines and related heterocycles. In this transformation, an O- to N-alkyl migratory rearrangement occurs to afford N-alkylated pyridones which are structures found in many natural products and pharmaceutical agents. Part III describes our pursuit of metal-catalyzed asymmetric synthesis. Readily available benzylic bromides are carbonylated with carbon monoxide in alcoholic solvent mixtures. The resulting medicinally relevant 2-arylpropionic esters are obtained with moderate to good enantioselectivities. Preliminary results for the asymmetric hydrogenation of gem-diarylethylenes and novel ligand development are also disclosed. Part IV describes our efforts towards the total synthesis of 6-deoxyerythronolide B. Our retrosynthetic analysis of the macrolide antibiotic involves disconnections at the lactone linkage and between C7 and C8. The two equally complex fragments were prepared via reliable aldol, hydroboration, crotylation and redox chemistry. Rather than the typical macrolactonization method to form the 14-membered ring, we propose an alternative strategy where we plan to cyclize with a metal-catalyzed ring-closing metathesis event. Currently, this step is under investigation by other members in the group.

5 Abstract Neuroblastoma is one of the most common cancer diseases diagnosed in children. This rapidly growing solid tumor is usually formed by hypoxic areas which arise as a consequence of inefficient and disorganized neovascularization. The cells stressed by hypoxia triggers transcription of many genes necessary for their survival, and conversely stop the production of proteins which are not necessarily needed for the survival in these severe conditions. The adaptation of cells to hypoxic conditions may appear due to the epigenetic regulation of metabolism associated with chromatin remodeling which involves the DNA methylation and also the posttranslational modifications of histones. Among the most important of these, there is the acetylation of lysine residues of histones associated with the DNA strands loosening, facilitated binding of transcription factors and the activation of gene expression. Thus, the first part of this study is concerned with changes in the acetylation of histones H3 and H4 of human neuroblastoma cell lines UKF-NB-3, UKF-NB-4, SH-SY5Y and SK-N-AS, cultured in parallel under standard culture conditions and in the absence of oxygen (hypoxia, 1% O2) for 24 hours, which are studied by Western blot analysis. Thereupon, the activity of histone deacetylases and histonacetyltransferases,...

Nitrogen availability and transformation in acidified and N saturated soils of Czech (The Bohemian Forest, Ore Mountains) and Ukraine (Pop Ivan massif) mountain forest ecosystems were investigated. The study was primarily focused on the role of microbial immobilization in soil N retention. The study was based on field measurements (ion exchange resins), analyses of selected soil biochemical and microbial characteristics, and on laboratory experiments (15N labelling).

L'utilisation de peptides en tant qu'agents thérapeutiques est une stratégie très répandue dans le domaine médical, en partie grâce aux propriétés pharmacologiques conférées par leurs structures tridimensionnelles. Des méthodes de fabrication de peptides rentables et respectueuses de l'environnement sont souhaitées pour répondre aux demandes du marché thérapeutique. Les azapeptides sont des analogues peptidiques dans lesquels un ou plusieurs atomes de carbone en α (α-C) d’un acide aminé sont substitués par un azote. Ils offrent des propriétés physicochimiques différentes qui augmentent le potentiel thérapeutique de peptides. La synthèse chimique peptidique traditionnelle se déroule du sens C-terminal vers Nterminal. Cette approche nécessite une utilisation importante de groupes protecteurs et de réactifs de condensation, ce qui crée des charges environnementales dues aux déchets chimiques. En outre, les peptides naturels biologiquement actifs présentent souvent une modification au niveau du C-terminal, ce qui rend ce type de modifications difficiles dans le sens classique de synthèse. Leurs synthèses dans le sens inverse peut surmonter ces limitations. Cependant, peu de travaux ont exploré la synthèse peptidique du côté N-terminal vers le côté Cterminal, en raison des épimérisations observées durant l’élongation peptidique. Dans ce mémoire nous démontrons le développement d’une nouvelle méthode pour la synthèse d’azapeptides du côté N-terminal vers le côté C-terminal sur support solide. Nous avons exploré deux voies de synthèses qui reposent sur l’incorporation d’un espaceur entre le support solide et le peptide. L’approche utilisée pour l’élongation peptidique se fera via l’hydrazinolyse du C-terminal protégé, suivie par une activation du couplage peptidique par un intermédiaire acyle d’azoture. L’hydrazinolyse servira également à l’incorporation du motif hydrazine au sein du squelette peptidique pour générer le motif azapeptide. En utilisant la méthionine comme initiateur de la synthèse peptidique, ces travaux ont démontré qu’il est possible de récupérer l’azapeptide synthétisé en utilisant la méthode de clivage de résine via le bromure de cyanogène. / The use of peptides as therapeutic agents is a widespread strategy in the medicinal field, in part due to pharmacological properties conferred by their three-dimensional structures. Costeffective and environmentally friendly peptide manufacturing methods are desired to address therapeutic market demands. Replacement of one or more of the alpha-carbon centers of the amino acid residues in a peptide by a nitrogen yields an azapeptide analog. This substitution may enhance peptide activity and selectivity. Azapeptides can also exhibit prolonged duration of action and increased metabolic stability. Traditional peptide synthesis uses C-terminal to N-terminal elongation. This approach requires significant use of protecting groups and condensation reagents, creating environmental burdens from chemical waste. In addition, biologically active natural peptides often feature a Cterminal modification, making this type of modification difficult to achieve using the classical sense of synthesis. To overcome these challenges, the concept of inverse chemical synthesis has been considered as an alternative for peptide production. However, its adoption has faced hurdles due in part to epimerization. In this study, we explore azapeptide synthesis in the N- to C-direction. Linker strategies were studied for azapeptide elongation in the inverse direction. Two pathways were explored using a spacer strategy between the solid support and the peptide to be elongated. The approach relies on peptide elongation by hydrazinolysis of C-terminal esters, activation and coupling via acyl azides. Hydrazinolysis is also used to incorporate the aza-motif into the peptide backbone. Using methionine as a precursor for azapeptide synthesis, this work demonstrated peptide cleavage using cyanogen bromide.