New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.

Prophecy as a narrative world : a study of the world-constructing conventions and narrative techniques in Hosea 1-3

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Chemical analysis of water samples of station M1_1207, Red Sea (Table 1-3)

Two water samples and two sediment samples taken in 1965 by the R. V. "Meteor" in the area of the hot salt brine of the Atlantis II-Deep were chemically investigated, and in addition the sediment samples were subjected to X-ray and optical analysis. The investigation of the sulfur-isotope-ratios showed the same values for all water samples. This information combined with the Ca-sulfate solubility data leads us to conclude that, for the most part, the sulfate content of the salt brine resulted from mixing along the boundary with the normal seawater. In this boundary area gypsum or anhydrite is formed which sinks down to the deeper layers of the salt brine where it is redisolved when the water becomes undersaturated. In the laboratory, formation of CaS04 precipitate resulted from both the reheating of the water sample from the uppermost zone of the salt brine to the in-situ-temperature as well as by the mixing of the water sample with normal Red Sea water. The iron and manganese delivered by the hot spring is separated within the area of the salt brine by their different redox-potentials. Iron is sedimented to a high amount within the salt brine, while, as evidenced by its small amounts in all sediment samples, the more easily reducible manganese is apparently carried out of the area before sedimentation can take place. The very good layering of the salt brine may be the result of the rough bottom topography with its several progressively higher levels allowing step-like enlargements of the surface areas of each successive layer. Each enlargement results in larger boundary areas along which more effective heat transfer and mixing with the next layer is possible. In the sediment samples up to 37.18% Fe is found, mostly bound as very poorly crystallized iron hydroxide. Pyrite is present in only very small amounts. We assume that the copper is bound mostly as sulfide, while the zinc is most likely present in an other form. The sulfur-isotope-investigations indicate that the sulfur in the sediment, bound as pyrite and sulfides, is not a result of bacterical sulfate-reduction in the iron-rich mud of the Atlantis II-Deep, but must have been brought up with the hot brine.

(Tables 1-3) Silicon dioxide, Corg and trace element concentrations in sediments of the outer Eckernfoerder Bay, Western Baltic Sea

The main question, posed in the work scheme before laboratory analysis was started, was expressed as follows: Do marked seasonal fluctuations occur in trace element content of the sediment surface, and what are the probable influences of factors such as changing hydrographical parameters, plankton sequence etc. ? Special attention was paid to elements known as pollutants, for example mercury. Within this framework samples have been analysed for their contents of manganese, iron, zinc, lead, and mercury. The amounts of silica and organically-bound carbon serve in most cases as reference values for the trace element content. On sand temporary conditions of increased C org content raise the concentrations of all determined elements. Especially the values reached for mercury in July are worth nothing. It is concluded that Zn, Pb, and Hg tend to enrich with respect to C org as the decomposition of organic matter progresses. On mud-sand flocculation and precipitation of Mn/Fe-hydroxides probably represent an additional concentrating factor for the other elements as the relationship of the results for zinc and manganese shows. Manganese may indicate a seasonally related concentrating cycle at the sediment surface.

Planktonic foraminiferal flux and shell geochemistry data in the sediment trap time series JAM 1-3 off south Java

Results from sediment trap experiments conducted in the seasonal upwelling area off south Java from November 2000 until July 2003 revealed significant monsoon-, El Niño-Southern Oscillation-, and Indian Ocean Dipole-induced seasonal and interannual variations in flux and shell geochemistry of planktonic foraminifera. Surface net primary production rates together with total and species-specific planktonic foraminiferal flux rates were highest during the SE monsoon-induced coastal upwelling period from July to October, with three species Globigerina bulloides, Neogloboquadrina pachyderma dex., and Globigerinita glutinata contributing to 40% of the total foraminiferal flux. Shell stable oxygen isotopes (d18O) and Mg/Ca data of Globigerinoides ruber sensu stricto (s.s.), G. ruber sensu lato (s.l.), Neogloboquadrina dutertrei, Pulleniatina obliquiloculata, and Globorotalia menardii in the sediment trap time series recorded surface and subsurface conditions. We infer habitats of 0-30 m for G. ruber at the mixed layer depth, 60-80 m (60-90 m) for P. obliquiloculata (N. dutertrei) at the upper thermocline depth, and 90-110 m (100-150 m) for G. menardii in the 355-500 mm (>500 µm) size fraction corresponding to the (lower) thermocline depth in the study area. Shell Mg/Ca ratio of G. ruber (s.l. and s.s.) reveals an exponential relationship with temperature that agrees with published relationships particularly with the Anand et al. (2003) equations. Flux-weighted foraminiferal data in sediment trap are consistent with average values in surface sediment samples off SW Indonesia. This consistency confirms the excellent potential of these proxies for reconstructing past environmental conditions in this part of the ocean realm.

(Tables 1-3) Geochemical composition of seepage water in soils obtained in Schleswig-Holstein, Germany

Under defined laboratory and field conditions, the investigation of percolating water through soil columns (podsol, lessive and peat) down to groundwater table shows that the main factors which control the chemical characteristics of the percolates are: precipitation, evaporation, infiltration rate, soil type, depth and dissolved organic substances. Evaporation and percolation velocity influences the Na+, SO4**2- and Cl- concentrations. Low percolation velocity leads also to longer percolation times and water logging in less permeable strata, which results in lower Eh-values and higher CO2-concentrations due to low gas exchange with the atmosphere. Ca2+ and Mg2+ carbonate concentration depends on soil type and depth. Metamorphism and decomposition of organic substances involve NO3 reduction and K+, Mg2+, SO4**2-, CO2, Fe2+,3+ transport. The analytical data were evaluated with multi variate statistical methods.

Novel free fatty acid receptor 1 (GPR40) agonists based on 1,3,4-thiadiazole-2-carboxamide scaffold

Free fatty acid receptor 1 (FFA1), previously known as GPR40 is a G protein-coupled receptor and a new target for treatment of type 2 diabetes. Two series of FFA1 agonists utilizing a 1,3,4-thiadiazole-2-caboxamide scaffold were synthetized. Both series offered significant improvement of the potency compared to the previously described 1,3,4-thiadiazole-based FFA1 agonists and high selectivity for FFA1. Molecular docking predicts new aromatic interactions with the receptor that improve agonist potency. The most potent compounds from both series were profiled for in vitro ADME properties (plasma and metabolic stability, LogD, plasma protein binding, hERG binding and CYP inhibition). One series suffered very rapid degradation in plasma and in presence of mouse liver microsomes. However, the other series delivered a lead compound that displayed a reasonable ADME profile together with the improved FFA1 potency.

Utemiljön som undervisningsverktyg inom matematiken : En studie om fyra lärares uppfattningar och användning av utomhusmatematik i årskurs 1-3

Syftet med denna studie var att undersöka hur lärares uppfattningar om utomhusmatematik som undervisningsmetod är i årskurserna 1-3 samt i vilken utsträckning de använder detta. De frågeställningarna som var bärande i studien var hur användandet av utomhusmatematik ser ut, vilka för- och nackdelar informanterna ser med utomhusmatematik, om något kunskapsområde inom matematiken lämpar sig bättre eller sämre vid användning av undervisningsformen samt om det är någon av de matematiska förmågorna eleverna lättare kan utveckla med detta. Metoden som tillämpades var kvalitativa semistrukturerade intervjuer med fyra lärare vilka har arbetat olika länge samt arbetar i delvis olika årskurser och på olika skolor. Resultatet visade att användande av utomhusmatematik inte är allt för stort men intresset för undervisningsformen är desto större. En bidragande orsak till att det inte används är storleken på klasserna idag. En fördel som informanterna ser med undervisningsformen är att eleverna får arbeta konkret, praktiskt, röra på sig samt att de får frisk luft. Med hjälp av utomhusmatematiken anser informanterna att både kunskapsområdena inom matematiken och de matematiska förmågorna går att utveckla med utomhusmatematik.

Effects of Purified Saccharomyces cerevisiae (1→3)-β-Glucan on Venous Ulcer Healing

Water-insoluble glucan was isolated from the baker’s yeast Saccharomyces cerevisiae. The yeast cells were treated with alkali and the residue then with acid. Chemical and NMR (1D and 2D) analyses showed that a linear (1→3)-β-glucan was purified that was not contaminated with other carbohydrates, proteins or phenolic compounds. The effects of the glucan on wound healing were assessed in human venous ulcers by histopathological analysis after 30 days of topical treatment. (1→3)-β-glucan enhanced ulcer healing and increased epithelial hyperplasia, as well as increased inflammatory cells, angiogenesis and fibroblast proliferation. In one patient who had an ulcer that would not heal for over 15 years, glucan treatment caused a 67.8% decrease in the area of the ulcer. This is the first study to investigate the effects of (1→3)-β-glucan on venous ulcer healing in humans; our findings suggest that this glucan is a potential natural biological response modifier in wound healing

Att utveckla elevers grundläggande begreppsförståelse i matematik : En litteraturstudie om hur matematikundervisningen i årskurs 1-3 kan utformas för att ge elever möjlighet att utveckla en god begreppsförståelse i matematik

Studier visar att svenska elevers resultat i matematik har försämrats och att en av de bakomliggande orsakerna till resultatnedgången är bristande begreppsförståelse. Samtidigt rapporteras det om att eleverna i undervisningen allt mer lämnas ensamma i sitt lärande i så kallat individuellt arbete. Tolkningen som kan göras är att det finns ett samband mellan elevers försämrade matematikkunskaper och undervisningen de möter i matematik. Syftet med denna studie är att få kunskap om hur matematikundervisningen kan utformas för att ge elever i årskurs 1-3 möjlighet att utveckla en god begreppsförståelse i matematik. Svaret söktes genom en systematisk litteraturstudie där litteratur och aktuell forskning söktes systematiskt. I studiens resultat exemplifieras en rad kommunikationsverktyg för läraren att använda direkt i undervisning, men också andra typer av verktyg, för att stödja och utveckla elevers förståelse för matematiska begrepp. Vidare synliggörs också fördelar med en lärare som möjliggör en undervisning där eleverna själva får kommunicera matematik och som agerar resurs för dem i deras övergång från det vardagliga till det matematiska språket. Kommunikation kan därför ses som ett viktigt verktyg i matematikundervisningen då det kommer till att utveckla elevers begreppsförståelse. Undervisningsmiljön behöver därför utformas till att passa en mer kommunikativ undervisning; en tillåtande miljö där eleverna tillåts och stöttas i att prata matematik.

Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria

Interaktiva skrivtavlor som redskap i No-undervisning : En litteraturstudie om interaktiva skrivtavlor i No i årskurserna 1-3

Syftet med litteraturstudien är att få kunskap om hur och till vad interaktiva skrivtavlor kananvändas som ett verktyg i No-undervisningen för årskurserna 1-3. Litteraturstudien undersökerockså om interaktiva skrivtavlor kan öka elevernas motivation och lärande i No. Eftersom mångakommuner i Sverige valt att satsa på olika digitala verktyg är det relevant att ta reda på vadforskningen säger om varför det är relevant att använda interaktiva skrivtavlor i Noundervisningen,på vilket sätt det gynnar eleverna. De frågeställningar som litteraturstudienkommer att utgå ifrån är: Vad säger tidigare forskning om varför pedagoger använder interaktivaskrivtavlor i undervisningen inom No i årskurserna 1-3? Vad säger tidigare forskning om hur ochtill vad pedagoger använder interaktiva skrivtavlor som verktyg i undervisningen för att ökamotivationen och lärande hos eleverna inom No i årskurserna 1-3? Metoden för studien är ensystematisk litteraturstudie och sökningarna för vald litteratur har skett i databaserna ERIC(Proquest) och Summon för att få fram relevant litteratur. Resultatet visar att det finns flerafördelar med att använda den interaktiva skrivtavlan i No-undervisningen i årkurserna 1-3. Någraav dessa fördelar är att kommunikationen i klassrummet ökar, att undervisningen lättare kanvarieras och att lärarna kan inspirera varandra. I diskussionen diskuteras bland annat om deninteraktiva skrivtavlan kan vara ett redskap för att förbättra resultatet för eleverna i No, dettaeftersom Pisa-undersökningarna visar att eleverna visar sämre resultat i No än tidigare.