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1
Weinstein, Randy D. (Randy David) 1971. "Organic synthesis in suppercritical carbon dioxide." Thesis, Massachusetts Institute of Technology, 1998. http://hdl.handle.net/1721.1/9652.
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Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1998.Includes bibliographical references (leaves 185-201).
Many industrially important synthesis reactions are carried out in liquid solvents such as aromatic compounds, chlorinated hydrocarbons, and other organic liquids which pose environmental and health hazards either because of their toxicity or their persistence in the environment. Hence proper disposal of these solvents and the prevention of accidental releases or routine emissions cause serious difficulties and costs for the industries who use them. An approach to mitigating these problems is to use alternative solvents that are environmentally benign or that can be completely recycled in a closed-loop process. One such alternative solvent is supercritical carbon dioxide. Although supercritical carbon dioxide is used in many industrial extraction and chromatography processes it is not widely used as a reaction medium and its effects on chemical reactions are not well understood. The goals of this research were to gain a better understanding as to the effect of supercritical carbon dioxide through a systematic investigation of solvent conditions on the rates and selectivities of several model organic synthesis reactions. In addition, the use of environmentally benign catalysts/promoters in gaseous and supercritical carbon dioxide as well as developing chemical pathways in which carbon dioxide can act as a solvent as well as a reactant were explored to expand the possible industrial applications. In the pursuit of these goals, new reactors, feed and sampling procedures, as well as new chemical pathways were explored. Specifically, the bimolecular rate constants of the Diets-Alder reaction of ethyl acrylate and cyclopentadiene were measured in supercritical carbon dioxide from 38 to 88 °C and pressures from 80 to 210 bar. At constant temperature, the rate increased with pressure or density and was most dramatic near the critical point of carbon dioxide. A traditional Arrhenius expression was used to correlate the kinetic data at a constant system density. All of the rate constant data were normalized to the rate constant at the same temperature and at a fixed density of 0.5 g/cm3. These normalized rate constants over a range of temperatures then collapsed on a single line as a function of density. Rates could be predicted using a bimolecular Arrhenius expression with the pre-exponential term having a linear dependence on density. Theoretically, a rigorous transition state theory rate constant was derived and used to gain a better understanding of the non-ideal solvent-reactant-product interactions which could influence the rate. Effects of pressure/density and temperature on the regio- and stereo- selectivity of several Diels-Alder reactions were explored. Regioselectivity did not correlate well with density changes; however, stereoselectivity did. As pressure was increased, the endo isomer always increased in the supercritical region. The stereoselectivity changes were modeled using temperature and density as the model inputs. Again, the rigorous transition state theory rate constant was used to explain the observed selectivity changes. Phase behavior played an important role in these investigations, sometimes influencing selectivity. The design and construction of reactors with a sapphire window allowed for visual access into the reaction environment to monitor phase behavior. Silica was shown to increase the rate and selectivity of several Diels-Alder reactions in carbon dioxide. Pressure/density effects were explored using the reaction of methyl vinyl ketone and penta-1,3-diene. Pressure did not affect the selectivity; however, it had a large effect on the yield of the reaction. This was discovered to be caused by the change in phase partitioning of the reactants between the fluid phase and the solid surface as pressure was changed. Adsorption isotherms at various pressures and temperatures were found. Because of the non-ideal system, the thermodynamic effect of temperature on the adsorption equilibrium needed to be derived. The effect of temperature on the adsorption was found at constant pressure. Although an enthalpy of adsorption could be determined, the presence of non-ideal phase behavior complicates its interpretation. In general, the adsorption enthalpy consists of partial molar enthalpies of both species (reactant and carbon dioxide) on/in both phases (solid/fluid). At constant density, the effect of temperature allows for the direct calculation of the entropy of adsorption. This term is affected by the partial molar entropies of both species on/in both phases. Three different carboxylation reactions were investigated in supercritical carbon dioxide. The Kolbe-Schmitt reaction (direct carboxylation of a phenolate salt) was found to proceed at high yields in supercritical carbon dioxide. Attempts at lowering the temperature of reaction by using cosolvents was not successful. Temperature and pressure had minimal effect on the selectivity of the reaction. Two other carboxylation reactions were examined. In the first study, the homogeneous catalyzed caboxylation of an allylsilane was performed in supercritical carbon dioxide. Pressure did not appear to affect the reaction; however, there was a narrow temperature range which allowed the reaction to proceed. At best, yields were only 15%. The final reaction studied was the catalyzed (Lewis acid) carboxylation of an alkene by carbon dioxide. Unfortunately it did not proceed in supercritical carbon dioxide to any measurable extent at temperatures of 40 to 350 °C with and without the presence of various catalysts.
by Randy D. Weinstein.
Ph.D.
2
Kimani, Flora, and Flora Kimani. "Triazabutadiene Chemistry in Organic Synthesis and Chemical Biology." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/620986.
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Triazabutadienes are nitrogen containing compounds with interesting acid-responsive behavior. These compounds are relatively stable, but once activated by an electrophile, for example through protonation, fall apart to yield diazonium and imine compounds. In general, diazonium compounds are unstable and require harsh methods of synthesis. Therefore, the use of triazabutadiene compounds as precursors to diazonium compounds, allows for a mild and more controlled access to this reactive moiety. This opens up diazonium chemistry to more complex chemical biology applications, as well as in the development of applications in organic synthesis. In an effort to design triazabutadiene systems that release diazonium compounds in physiological conditions, water-soluble imidazolium-based triazabutadienes were synthesized by coupling N-heterocycle imidazolium carbenes to aryl azides. These compounds were shown to have pH-dependent reactivity, generating aryl diazonium salts in buffered solutions ranging from pH 4-7. This reactivity made these compounds one of the mildest ways of generating aryl diazonium salts in aqueous solutions. Initial stability and reactivity studies were performed by NMR, and by altering the sterics of the imidazolium core and the electronics of the phenyl group. It was determined that the rate and stability were influenced by the sterics and electronics of the scaffold. Electron withdrawing substituents on the phenyl and steric bulk on the imidazole core resulted in stable triazabutadienes, with the opposite being observed for the electron donating substituents on the phenyl and small substituents on the imidazole. Water-soluble triazabutadienes were synthesized to be further utilized as chemical biology probes. In organic solvents, the triazabutadienes reacted with resorcinol, an electron-rich phenyl group to form stable azo compounds. In more physiologically relevant conditions, the triazabutadiene compound was stirred in a pH 6 phosphate/citric buffer solution with a tyrosine analogue and an azo adduct was isolated. This indicated it was possible to target tyrosine residues with a triazabutadiene delivered aryl diazonium through the formation of azo bonds that could be cleaved under mild reducing conditions using sodium dithionite. In addition, the triazabutadiene compounds were found to undergo light-induced isomerism generating the Z isomer in solution upon irradiation. The Z isomer was observed to be more reactive, and would degrade even in basic solutions when irradiated with 350 nm light. This light responsiveness was utilized to enhance the reactivity of triazabutadiene attached onto protein and viral surfaces, allowing the generation and capture of aryl diazonium salts by electron rich aryl-fluorophore conjugates as well as antibody proteins in the case of the virus. Alkyl triazabutadiene compounds were synthesized by coupling N-heterocycle carbenes onto alkyl azides. These compounds were then shown to be capable of delivering alkyl diazonium compounds to carboxylic acids for esterification. This method diversifies esterification from only methyl substituents, as is the case with diazomethane and TMS-diazomethane, to larger more diverse alkyl groups. In conclusion, this work shows that the triazabutadiene compounds have interesting activity that will be vital in the development of novel probes for the study of biological process, as well as the development of reagents for chemical synthesis.
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Rickards, Andrew M. J. "Hygroscopic organic aerosol : thermodynamics, kinetics, and chemical synthesis." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686238.
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Aerosols play a crucial role in many areas of scientific relevance including in new technologies to deliver medicine to the lungs, and in fuel injection and spray drying. Aerosols have a profound impact on the atmosphere, influencing radiative forcing both by scattering solar radiation and by influencing cloud properties. Organic aerosols are a major component, making up 20 - 90 % of the submicron mass by region, and are emitted from many natural and anthropogenic sources. This thesis presents new measurements of the hygroscopic behaviour of single organic droplets confined using two techniques: aerosol optical tweezers (AOT) and an electrodynamic balance (EDB). Values of the hygroscopicity parameter (K) are derived and added to a comprehensive literature survey to elucidate a relationship with droplet composition, in terms of the molecular ratio of oxygen to carbon atoms (OIC). These data are shown to be in broad qualitative agreement. However, variation in K for droplets of the same OIC is found to be significant, and discrepancies between subsaturated and supersaturated data are evident. The variabilities and uncertainties associated with characterising the kinetics of water transport in ultraviscous sucrose droplets are also presented. Droplets are exposed to a perturbation in relative humidity, and the resultant characteristic relaxation timescale (r) is determined from stimulated Raman spectra. Comparison of the experimental· evaporation data with simulated timescales shows excellent agreement, and r is shown to increase strongly with droplet radius. Qualitative agreement between experimental condensation data and simulated timescales is presented, and r is shown to increase with wait time (the time the perturbation is applied for). Finally, factors influencing the ability to perform controlled chemical synthesis in single droplets are investigated. The formation of Nylon-6,1 0 at the droplet-gas phase interface is used as a test case of the system, and the interplay between droplet volatility and reactivity is shown to be crucial for controlling the reaction. Further investigations demonstrate synthesis of picomolar concentrations (equivalent to a single dose) of a functionalised caprolactam anti-cancer drug. The challenges in reliably validating drug formation in aerosol are presented.
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McMurray, Brian Thomas. "Chemical and enzymatic synthesis of organosulphur compounds." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359111.
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Lee, Wen-Hsuan Ph D. Massachusetts Institute of Technology. "Development of microreactor setups for microwave organic synthesis." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/98157.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2015.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 135-140).
The main contribution of this work is the understanding of microwave heating and the microreactor design challenges involved through both chemical experiments and computational models. The original goal of this research is to develop a microreactor system in order to carry the microwave organic synthesis in continuous flow format and to understand the basic phenomena of microwave heating through accurate kinetic studies. Several heating issues were observed with the first microreactor setup, including an uneven temperature distribution across the microwave irradiated area and a temperature limitation that depends on the position of the reactor. To find the root of these problems, the electromagnetic field and the heat transfer scheme of the microwave system were modeled with COMSOL. The simulations show that there are three main causes to the heating issues: (1) the electric field has an inherent resonance structure and thus has an uneven magnitude within the microwave cavity, (2) the electric field changes with not only the material, but also the sizes and positions of the objects in the microwave cavity, (3) the air gaps in the microwave waveguide creates a large natural convection heat loss. The simulations gave us a deeper understanding of the microwave heating phenomena and were used to find the optimum design of the microreactor. A second multiple-layered glass reactor was designed accordingly to overcome the heating limitation and minimized the temperature unevenness. However, the non-uniform heating rate cannot be eliminated since it is inherent in the resonance structure of microwaves. Both the experimental results and the simulations of the final reactor show that even though the reactor can reach the desired temperature, the temperature range across the reactor could be up to 20 *C. In addition, it was found that the flow rate of the reaction greatly affects the thermal equilibrium of the reaction volume. Accurate temperature control is therefore still a challenge for kinetic studies to be feasible with the current single-mode microwave system. The benefit of microwave heating is therefore still in the qualitative screening of chemical compounds, a feature which was demonstrated with a Fischer-Indole screening in the final setup.
by Wen-Hsuan Lee.
Ph. D.
6
Murphy, Edward R. "Microchemical systems for rapid optimization of organic synthesis." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/36912.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2006.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (leaves 111-119).
In the chemistry laboratory, the desire to use smaller quantities of material to minimize both reagent cost and waste generation has driven chemists to develop new experimental techniques. The current approach to small scale experimentation has mostly been a simple reduction in the size of batch reaction apparatus. Working with these smaller volumes has increased the efficiency of experiments by accelerating the typically time consuming processes of heating, filtration, and drying. Furthermore, when working with hazardous materials, smaller scales minimize the exposure of a chemist to toxic materials and enable easier containment of potentially flammable or explosive systems. The use of microfluidic devices has shown several improvements when compared to traditional batch synthesis. The precise control of reaction conditions enabled within the microreactor format has proved advantageous for a wide range of single and multiphase reactions. Also, unlike conventional bench-top batch reactions, continuous microreactors are capable of producing both analytical and preparative quantities of material by simply changing the amount of reactor effluent collected.
(cont.) The aim of this work was to harness the microsystem advantages of improved safety and process intensification while demonstrating both improved quality and speed of data collection, especially for chemistries that were challenging to explore using standard laboratory techniques. This work required improvements to reactor design, packaging technologies, and experimental techniques in order to use microreactors as a platform for rapidly determining optimum reaction conditions as well as reaction kinetics. Three model reactions were selected to highlight the advantages of microchemical laboratory tools. The synthesis of oligosaccharides served as an example of rapid profiling of the effects of temperature and reaction time. Microreactors improved reaction optimization by reducing waste and dramatically increasing the rate of data collection. High-pressure carbonylation of aryl halides was also explored to characterize the effects of pressure, temperature, and various substrates on product yields. With microreactors, previously inaccessible reaction conditions were explored thus obtaining improved insights into the reaction mechanism.
(cont.) Finally, the production of sodium nitrotetrazolate was used to demonstrate the improved flexibility and safety of a modular microchemical system. The kinetics and pH effects for each step of the synthesis of this energetic compound were measured. This system was also optimized so that the microreactors used to characterize the reaction could be run in parallel as a production method.
by Edward Robert Murphy.
Ph.D.
7
Coley, Connor Wilson. "Computer assistance in organic synthesis planning and execution." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122903.
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This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2019
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 409-432).
The identification and synthesis of molecules that exhibit a desired function is an essential part of addressing contemporary problems in science and technology. Small molecules are the predominant solution to challenges in the development of medicines, chemical probes, specialty polymers, and organocatalysts, among others. The typical discovery paradigm is an iterative process of designing candidate compounds, synthesizing those compounds, and testing their performance. The rate at which this process yields successful compounds can be limited by bottlenecks and mispredictions at all three stages and is plagued by inefficiencies, not the least of which is the manual nature of synthesis planning and execution. This thesis describes techniques to streamline the synthesis of small molecules in this context of pharmaceutical discovery from two perspectives: one experimental and the other using techniques in data science and machine learning.
Part I focuses on the time-, material-, and experimental-efficiency of data collection. It describes the development of an automated microfluidic reactor platform for studying physical and chemical processes at the micromole scale. Synthesis and purification of small molecule compound libraries are performed without human intervention at a scale suitable for a medicinal chemistry setting. Integration of online analytics enables efficient, closed-loop self-optimization using an optimal design of experiments algorithm to identify reaction conditions suitable for production-scale flow synthesis. To complement the generation of new data through automated experimentation, Part II is driven by the goal of applying existing reaction data to problems in synthesis and synthesis design. This includes the development of data-driven methodologies for the design and validation of small molecule synthetic routes.
An enabling factor in ensuring the feasibility of computationally-proposed reactions is the use of models to predict organic reaction outcomes in silico-also useful for impurity prediction-that leverage the flexibility in pattern recognition afforded by neural networks to understand chemical reactivity in the same way we might by reading the literature. Several predictive models are integrated into an overall framework for computer-aided synthesis planning that can rapidly propose routes to new molecules with the complexity of modern active pharmaceutical ingredients. As a final demonstration, machine learning assisted synthesis planning is brought together with laboratory automation to illustrate an accelerated approach to target-oriented flow synthesis. This is a proof-of-concept for how chemical development might one day occur with less human intervention.
by Connor Wilson Coley.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Chemical Engineering
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Olugbenga, F. S. "Synthesis and physico-chemical studies on conjugated heteroenoid compounds." Thesis, Cardiff University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.332625.
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Woodcock, Steven Robert. "Synthesis and chemical biology of nitrated lipids /." view abstract or download file of text, 2007. http://proquest.umi.com/pqdweb?did=1324377731&sid=2&Fmt=2&clientId=11238&RQT=309&VName=PQD.
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Thesis (Ph. D.)--University of Oregon, 2007.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 195-207). Also available for download via the World Wide Web; free to University of Oregon users.
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Collins, Beatrice Samora LeFanu. "New catalytic methods and strategies for chemical synthesis." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648556.
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Tucić, Aleksandar. "Wet chemical synthesis and characterization of organic/TiO 2 multilayers." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-34138.
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Loke, P. L. "Chemoenzymatic and chemical synthesis of enantiopure quinoline derivatives and alkaloids." Thesis, Queen's University Belfast, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273295.
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Carriero, Sandra. "Chemical synthesis and biological evaluation of circular, branched and lariat oligonucleotides." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84488.
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This thesis highlights novel synthetic routes towards the facile synthesis of lariat DNA and RNA oligonucleotides, and the utilities of branched (bNAs) and circular (i.e. dumbbell-shaped) nucleic acids for targeting biologically relevant processes (i.e. HIV proliferation, alternative RNA splicing) with potential therapeutic applications.An innovative synthetic strategy for the synthesis and cyclization of a medium-sized (21-nucleotide) DNA lariat starting from a CPG-tethered, convergently synthesized branched DNA (bDNA) molecule was devised in Chapter 2. This synthetic route exploited the differential cleavage rates of two CPG-oligonucleotide tethers, namely the base-labile hydroquinone-O,O'-diacetate (Q-linker) and the more robust succinate (S-linker ) linkages, as well as phosphitylation of the 5'-oligonucleotide terminus and cyclization under standard phosphoramidite coupling conditions to effect new phosphodiester bond construction. The results clearly indicate a disadvantageous correlation between high branching efficiency on a densely loaded CPG and the production of dendrimeric (i.e. hyperbranched) oligonucleotide species rather than effective cyclization.
Given the entropic disadvantage of synthesizing medium-sized DNA lariats on solid-support using the method described in Chapter 2, unique intermolecular (i.e. DNA dumbbells) and intermolecular template-mediated approaches for lariat cyclization commencing with convergently and divergently synthesized bDNAs and bRNAs were developed in Chapter 3. Both methods lead to the exclusive and high-yielding formation of medium sized (46--57 nucleotides) DNA and RNA lariats. Parameters for successful phosphodiester bond construction were also elucidated in both systems.
A novel class of highly specific and potent oligonucleotide-based HIV-1 reverse transcriptase inhibitors, RNA dumbbells, comprising of a 10 base-pair stem and two flanking UUCG hairpin-loop motifs are described in Chapter 4. Explicitly, such constructs were capable of selectively hampering the RNase-H mediated activity of the retroviral enzyme without consequence to its DNA polymerase function with an IC50 in the 3 muM range. Its precise interaction with the RNase H domain of RT was authenticated via a UV-crosslinking assay. Furthermore, the RNA dumbbells did not inflict any effect on mammalian RNase H activity, suggesting that such compounds would not obstruct cellular RNase H function.
Chapter 5 describes the utility of synthetic bRNA for the inhibition and modulation of pre-mRNA splicing in yeast and mammalian in vitro systems. Most notably, synthetic bNAs can be suitably exploited as agents for the study of branchpoint recognition during in vitro splicing of a pre-mRNA transcript. The results clearly indicate the requirement for a fully formed branchpoint (i.e. 5 '-, 2'- and 3'-extensions; Y-shaped molecules) off the conserved branchpoint adenosine for efficient splicing inhibition. Specific methods for stabilizing bNAs against ubiquitous cellular exo- and endonucleases as well as the 2'-scissle (2'-debranching) activity present in the HeLa extract milieu are also described.
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Mohamed, Nazim. "Synthesis of derivatized oxopiperazines from amino acids." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0016/NQ44518.pdf.
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Ferguson, Ronald Dale 1966. "Design, synthesis and biological screening of combinatorial chemical libraries." Thesis, The University of Arizona, 1996. http://hdl.handle.net/10150/278584.
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Although combinatorial libraries owe their inception to applications in peptide and bacteriophage libraries, the breadth of current applications include solution phase chemical reaction optimization, material science investigation, natural products modifications, and agricultural research. As a conceptual application, combinatorial library techniques can enhance a researcher's ability to transcend beyond the examination of one or several compounds to that of thousands or millions of these species simultaneously. The work described here, limited to scaffolded combinatorial chemical libraries, focuses primarily on the design and synthesis of these systems and how they have been analyzed against biological targets. Of the three scaffolded libraries, two were developed from aromatic templates (3,5-diaminobenzoic acid and 1,2,4-benzenetricarboxylic acid) while the last was built upon the cyclohexyl, Kemp's triacid platform. Although these libraries did not provide compounds with high affinity for the receptors investigated, they served to improve the understanding of combinatorial chemistry as a practice.
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Millington, Christopher Russell. "Novel linkers for the solid phase synthesis of combinatorial chemical libraries." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299225.
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Theberge, Ashleigh Brooks. "Droplet-based microfluidics for chemical synthesis and integrated analysis." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609687.
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Maguire, Nuala Margaret. "Chemical preparations, enzymatic syntheses and pericyclic reaction of (13S)-HODE and derivatives." Thesis, University of Exeter, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.332299.
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Guillemard, Véronique. "Design and chemical synthesis of selective cancer therapeutics." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85073.
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The clinical use of chemotherapeutic agents against malignant tumors is successful in many cases but suffers from major drawbacks. One drawback is the lack of selectivity which leads to severe side effects and limited efficacy, and another is the emergence/selection of drug-resistance. To limit non-specific toxicity and to improve the efficiency of cancer therapy, "tumor markers", which are proteins generally overexpressed on the surface of tumor cells, can be selectively targeted.Growth factor receptors are one of the most extensively studied groups of tumor markers. The implication of growth factor receptors in the pathogenesis of cancer has clearly been established and therefore, provides a rationale for therapeutic intervention. The targeting of cytotoxic substances to defined cell populations with "magic bullets" is an old idea that raised high expectations but also disappointment. Over the past decade, newly gained understanding of mechanisms for targeted therapy have brought new hopes. Pharmacological agents that selectively target and block the action of growth factors and their receptors have been attempted, such as monoclonal antibodies (mAbs) (whole molecule or fragments), bispecific antibodies, mAbs conjugated to drugs, toxins or radioisotopes, small peptidic and peptidomimetic molecules in free form or conjugated to drugs, anti-sense oligonucleotides, immunoliposomes-encapsulated drugs, and small molecule inhibitors. We designed, synthesized and characterized new chemotherapeutic agents consisting of Paclitaxel or Doxorubicin as anti-cancer drugs chemically coupled to growth factor receptor-selective monoclonal antibodies or small peptides as targeting agents. We show that the conjugates were selective and specific towards the targeted receptors, and had significant increased efficiency compared to parent drugs. More importantly, the conjugates were able to bypass p-glycoprotein-mediated resistance both in vitro and in vivo. These findings have considerable importance since drug resistance is a major cause of cancer treatment failure.
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Zsótér, András. "Robotic chemical synthesis using forth as an interactive development environment /." Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17492695.
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Kewley, Adam. "The synthesis and separation properties of organic cage compounds." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2010659/.
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Microporous materials play an important role in a variety of industrial and domestic applications. While a diverse range of microporous materials have been identified, this thesis focuses on porous organic cages (POCs) because they have received much attention as synthetically tunable, solution processable, microporous materials. After introducing the latest developments in POC synthesis and the general application of microporous materials as selective sorbents, this thesis presents three developments in organic cage chemistry: a high-throughput workflow for the discovery of POCs, which yielded a novel organic cage compound; the measurement of selective adsorption by POCs, wherein the first instance of chiral selectivity by a POC was recorded; and the first instance of applying POCs as stationary phases for gas chromatography, which produced columns that separate racemic mixtures, alkylaromatic isomers, and alkane isomers. Chapter 2, discovering novel organic cages, presents attempts to use high-throughput and in-silico techniques to accelerate the discovery of novel organic cages. These methods were utilised to isolate a novel organic cage, CCX-S, which is characterised and discussed. Chapter 3, organic cages as selective sorbents, presents the development of approaches for measuring selective adsorption. These methods were used to identify the first reported instance of enantioselective adsorption by an organic cage. Further measurements to explain this separation behavior are also presented. Chapter 4, chromatographic separations with organic cages, presents one method of practically leveraging the presented separation behavior. In Chapter 4, the coating of capillary columns with CC3 is presented. These columns were used to successfully perform gas chromatographic separations, the first recorded instance of using a POC to do so. The columns were further improved by modifying the coating method and using prefabricated CC3 nanoparticles. This modification enabled difficult separations to be performed using the column; for example, the separation of hexane’s five isomers.
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McCarten, Paul. "Synthesis and reactivity of alpha-heteroaton substituted organoiron compounds." Diss., Georgia Institute of Technology, 1988. http://hdl.handle.net/1853/30503.
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Folkins, Patricia L. (Patricia Lorna). "The synthesis, structure and chemical reactivity of cyclic and bridged bicyclic sulfur-containing herterocycles." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39272.
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A general synthesis for bridged bicyclic disulfide compounds was refined and expanded from (3.2.1) to (4.2.1) and (2.2.1) systems. Various derivatives were synthesized through modification of the hydroxyl functionality in these molecules. The oxidation of all bridged bicyclic disulfide compounds to their corresponding bridged bicyclic thiosulfinate esters (a previously unknown class of compounds) was performed. Three crystal structures were obtained and selected bond lengths, bond angles and torsion angles were compared with the calculated values obtained using MMX molecular mechanics via the PCMODEL program.The m-CPBA oxidation of the above bridged bicyclic thiosulfinate esters was followed at low temperature using $ sp1$H and $ sp{13}$C NMR spectroscopy. $ alpha$-Disulfoxides were detected as the first intermediates in this oxidation process and were seen at temperatures and concentrations greater than any previously reported. Strong evidence was also found to suggest the intermediacy of O,S-sulfenyl sulfinates. A clear mechanistic proposal for the rearrangement of bridged bicyclic $ alpha$-disulfoxides to their corresponding thiosulfonate esters was presented based on experimental results.
Attempts towards the synthesis of the bridged bicyclic disulfide analogue of ergosterol peroxide using diatomic sulfur methodologies were reported. These attempts were not successful.
The generation of the pseudo-diatomic species, R-P = S (thioxophosphanes), using a methodology previously developed in our laboratory was examined. The thioxophosphanes (R = C$ sb6$H$ sb5$, C$ sb2$H$ sb5$ and p-Cl-C$ sb6$H$ sb4$) were trapped with 1,3-dienes to give cyclic and bridged bicyclic thiophosphoranes.
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Lawandi, Janice. "Development and application of chemical tools for the design and synthesis of bioactive molecules." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=92314.
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In the field of drug design and development, medicinal chemists use a variety of tools to quickly generate a series of hit compounds controlling a specific biological target and culminating in a lead compound. Process chemists seek efficient methods to synthesize the lead compounds provided by the medicinal chemists and using readily available and inexpensive starting materials, shortcuts and simpler routes. With this in mind, we aimed to design, develop and apply chemical tools to generate hit compounds, but also developing new simpler methods to make pharmaceutically relevant compounds. In this context, this thesis has two goals. In the first part, we focused on the enzyme prolyl oligopeptidase, reviewing its involvement in neurological disorders, such as Alzheimer's disease, and the efforts of several researchers to synthesize potent, selective inhibitors resembling the natural substrates of this enzyme. We proposed another method, using small pseudopeptidic and peptidomimetic inhibitors as chemical tools to better understand the shape, size and electronics of inhibitors and generate a more potent, selective prolyl oligopeptidase inhibitor. From our series of compounds, we discovered a few potent and highly selective, covalent inhibitors, one of them pseudo-peptidic (IC50 = 3-7 nM) and the other peptidomimetic (IC50 = 20-700 nM). In the second part of this thesis, with the goal of being able to exploit sugars in medicinal chemistry, we first reviewed the methods that exist to regioselectively functionalize the various hydroxyls of hexopyranosides. We compiled these methods into a table which chemists could consult when they are seeking to perform a specific reaction on a specific sugar. We then proposed to use a hydrogen bond accepting protecting group which can direct subsequent reactions to specific sites on sugars in an effort to reduce the number of protection and deprotection steps. We applied this protecting-directing group and developed methods to regioLors de la conception d'un nouveau principe actif, les chimistes médicinaux disposent d'un grand nombre d'outils leur permettant de générer rapidement une série de composés ayant une action spécifique. L'optimisation du procédé chimique requiert l'utilisation et le développement de méthodes toujours plus simples, rapides et peu couteuses. Ainsi, nous avons souhaité concevoir et utiliser quelques outils chimiques permettant de résoudre certains de ces problèmes. Cette thèse présente des outils spécifiques à la chimie médicinale et la chimie des procédés. Dans un premier temps, nous nous sommes intéressés à une enzyme : la prolyl oligopeptidase. Nous avons tout d'abord répertorié un grand nombre de données, quant à son implication dans certains troubles neurologiques (ex. : maladie d'Alzheimer), ainsi que de nombreux programmes de recherche visant le développement de nouveaux inhibiteurs conçus à partir de la structure du substrat naturel. Dans l'optique de mieux comprendre l'environnement chimique du site de liaison de l'enzyme et concevoir notre propre inhibiteur sélectif, nous avons synthétisé et testé une série de composés pseudo-peptidiques et peptidomimétiques. Lors de cette étude, nous avons identifié deux inhibiteurs covalents, actifs et sélectifs : l'un pseudo-peptidique (IC50 = 3-7 nM), l'autre peptidomimétique (IC50 = 20-700 nM). Dans la deuxième partie de cette thèse, nous avons rapporté les méthodes déjà existantes permettant une fonctionnalisation régioselective des différents groupements alcools des hexopyranosidases afin de rendre plus accessible l'utilisation des sucres en chimie médicinale. La compilation de cette recherche bibliographique dans une table permettra aux chimistes de facilement sélectionner la méthode la plus adéquate. Afin de réduire le nombre d'étapes (protections et déprotections) associées à la chimie des sucres, nous avons appliqué le groupement protecteur-directeur dév
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Mciteka, Lulama Patrick. "Novel applications of Morita-Baylis-Hillman methodology in organic synthesis." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1007598.
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The overall approach in the present investigation has been to explore applications of the Morita-Baylis-Hillman (MBH) reaction in asymmetric synthesis and in the continuation of systems with medicinal potential. To this end, a series of varied camphor-derived acrylate esters was prepared to serve as chiral substrates in asymmetric Morita-Baylis- Hillman reactions. Reduction of N-substituted camphor-10-sulfonamides afforded the 3- exo-hydroxy derivatives as the major products. Acylation of the corresponding sodium alkoxides gave the desired 3-exo-acrylate esters, isolation of which was complicated by concomitant formation of hydrochlorinated and diastereomeric competition products. Bulky camphorsulfonamides containing alkyl, dialkyl, aromatic and adamantyl groups were selected as N-substituents with the view of achieving stereoselective outcome in subsequent MBH reactions. The synthesis of novel camphor-derived Morita-Baylis-Hillman adducts using various pyridine-carboxaldehydes proceeded with exceptionally high yields with diastereoselectivities ranging from 7-33 % d.e. Both 1D and 2D NMR and HRMS techniques were employed to confirm the structures and an extensive study of the electropositive fragmentation patterns of a number of camphor-derived chiral acrylate esters was conducted. Attention has also been given to the application of MBH methodology in the construction of heterocyclic ‘cinnamate-like’ AZT conjugates which were designed to serve as dualaction HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. A number of pyridine carboxaldehyde-derived MBH adducts were synthesized using methyl, ethyl and t-butyl acrylates in the presence of 3-hydroxyquinuclidine (3-HQ) as catalyst. The yields for these reactions were excellent. The resulting MBH adducts were acetylated and subjected to aza-Michael addition using propargylamine. The resulting alkylamino compounds were then used in ‘Click reactions’ to form the targeted AZT-conjugates in moderate to excellent yield. In silico docking of computer modelled AZT-conjugates into the HIV-1 integrase and reverse transcriptase enzyme-active sites and potential hydrogen-bonding interaction with active-site amino acid residues were identified. The electrospray MS fragmentations of the AZT and the novel AZT-conjugates were also investigated and common fragmentation pathways were identified.
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Davis, Randon Emerson. "Development and Synthesis of 7-Alkylguanosine Pronucleosides for Application in Chemical Solid-State Oligoribonucleic Acid Synthesis." Kent State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1595274318375068.
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Zsótér, András. "Robotic chemical synthesis using forth as an interactive development environment." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31235505.
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Oh, Young-im. "Approaches to the synthesis of the oxa-bridged germacrane ring system." Diss., Georgia Institute of Technology, 1988. http://hdl.handle.net/1853/27566.
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Bentley, Scott Alexander. "Asymmetric conjugate addition reactions." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:9e619a66-6277-48c2-8a2e-24f8206e52b3.
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This thesis is concerned with the asymmetric conjugate addition reactions of a range of chiral nucloeophiles. Chapter 1 introduces the conjugate addition reaction as a valuable carbon-carbon and carbon-heteroatom bond forming reaction in organic chemistry, and explores the asymmet- ric conjugate addition of a range of chiral and achiral carbon and nitrogen nucleophiles to a range of acceptors. Chapter 2 explores the use of the N-benzyl-N-(α-methylbenzyl)amino group as a chi- ral auxiliary, by employing the attempted conjugate additions of both N-benzyl-N-(α- methylbenzyl)hydrazine and N -benzyl-N -(α-methylbenzyl)hydroxylamine as chiral ammo- nia and water equivalents respectively. Chapter 3 describes the asymmetric and stereoselective preparation of a range of 4,4- disubstituted isoxazolidin-5-ones from the conjugate addition of lithium (S)-N-tert-butyl- dimethylsilyloxy-N -(α-methylbenzyl)amide. The isoxazolidin-5-ones are then globally de- protected via hydrogenolysis, giving rise to the corresponding β2,2,3-amino acids. Chapter 4 focuses on the development of a protocol to effect the conjugate addition of a chiral aniline equivalent. The scope of the reaction is delineated by varying both the nu- cleophile and the α,β-unsaturated ester. Finally, cyclisation of the β-N-arylamino esters to the corresponding tetrahydroquinolines is explored, and an application to the synthesis of the natural product (−)-angustureine is presented. Chapter 5 contains full experimental procedures and characterisation data for all com- pounds synthesised in Chapters 2, 3 and 4.
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Zavahir, Fathima Sifani. "Development of visible light photocatalysts for organic fine chemical production." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/96049/1/Fathima%20Sifani_Zavahir_Thesis.pdf.
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Devising new photocatalysts that can harvest light energy to drive chemical processes is in the forefront of chemical research. It aims at limiting the use of depleting fossil fuel energy, better understanding optical properties of materials and developing green chemical synthesis processes. During this doctoral work, three different types of photocatalysts, based on titanium dioxide, gold nanoparticles and vanadium clusters, have been designed and evaluated for synthetically important organic chemical reactions under visible light irradiation at near ambient conditions.
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Cuesta, Aluja Laia. "Towards green synthesis of organic carbonates: Utilization of CO2 as a chemical feedstock." Doctoral thesis, Universitat Rovira i Virgili, 2015. http://hdl.handle.net/10803/401818.
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La present Tesi doctoral es basa en l'ús de diòxid de carboni tant com a matèria prima per a la síntesi de carbonats cíclics i policarbonats d'alt valor afegit, com a dissolvent alternatiu. S'ha estudiat el potencial de diferents sistemes catalítics metàl·lics, destacant l'alta activitat i selectivitat; l'ús de condicions suaus i catalitzadors favorables per el medi ambient i, també, l'aclariment del mecanisme de reacció centrant-se en el paper de cada component catalític.
S'ha descrit l'alt potencial catalític dels complexes amb baixa toxicitat i gran abundància terrestre com per exemple, els complexos d' Al(III) i Fe(III) amb lligands tetradentats N2O2; i els complexes de Zn(II) i Fe(III) amb lligands tridentats NN'O.
A més, en el transcurs d'aquesta Tesi es va aconseguir l'obtenció de carbonat de metil oleat, derivat d'olis naturals, mitjançant els complexes d'Al(III), Zn(II) i Fe(III).
D'altra banda, es van trobar que els complexes de Fe(III) són actius tant per l'epoxidació d'olefines i la síntesi de carbonats orgànics. Així mateix, es va realitzar un estudi preliminar sobre la carboxilació oxidativa de l'estirè per a l'obtenció de carbonat d'estirè utilitzant scCO2 tant com a reactiu i solvent amb un complex de Fe(III) amb lligand tridentat NN'O.La presente Tesis doctoral se centra en el uso de dióxido de carbono tanto como materia prima para la síntesis de carbonatos cíclicos y policarbonatos de alto valor añadido, como disolvente alternativo. Se ha estudiado el potencial catalítico de diferentes sistemas catalíticos metálicos, destacando la alta actividad y selectividad; el uso de condiciones suaves y catalizadores favorables para medio ambiente y, también, el esclarecimiento del mecanismo de reacción centrandose en el papel de cada componente catalítico. Se ha descrito el alto potencial catalítico de los complejos con baja toxicidad y gran abundancia terrestre como por ejemplo, los complejos de Al(III) y Fe(III) con ligandos tetradentados N2O2; y los complejos de Zn(II) y Fe(III) con ligandos tridentados NN'O. Además, en el transcurso de esta Tesis se logró la obtención de carbonato de metil oleato, derivado de aceites naturales, mediante los complejos de Al(III), Zn(II) y Fe(III). Por otra parte, se encontraron que los complejos de Fe(III) son activos tanto para la epoxidación de olefinas y la síntesis de carbonatos orgánicos. Asimismo, se realizó un estudio preliminar sobre la carboxilación oxidativa del estireno para la obtención de carbonato de estireno utilizando scCO2 tanto como reactivo y solvente con un complejo de Fe(III) con ligando tridentado NN'O.
This doctoral Thesis was focused on the use of carbon dioxide as both C1 building block for the synthesis of useful cyclic carbonates and polycarbonates and its uses as a plausible alternative solvent. We studied the catalytic potential of different metal-catalyzed systems, highlighting the high catalytic activity and selectivity; the use of mild conditions and environmentally friendly metal catalysts and also the elucidation of the possible reaction mechanism giving a plausible catalytic role of each component. It was described the high potential of a low-toxic and earth-abundant Al(III) and Fe(III) complexes bearing tetradentate N2O2-donor ligand whereas the high activity of Zn(II) and Fe(III) complexes bearing tridentate NN'O-donor ligands. An important and greener goal of this Thesis was the obtention of methyl oleate carbonate, derived from natural oils, with those metal earth abundant Al(III), Zn(II) and Fe(III) complexes. Moreover, iron complexes were found to be active both for olefin epoxidation and organic carbonate synthesis. A preliminary study of direct oxidative carboxylation of styrene towards styrene carbonate using scCO2 as both reactive and solvent with Fe(III) complex bearing NN'O-donor ligand was undertaken.
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Tucić, Aleksandar [Verfasser]. "Wet chemical synthesis and characterization of organic, TiO2 multilayers / vorgelegt von Aleksandar Tucić." Stuttgart : Max-Planck-Inst. für Metallforschung, 2008. http://d-nb.info/995389497/34.
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Elemia, Freire Constancia Felise, Simon Edin, and Chang Ho Lee. "SPME Method for Chemical Analysis of Heavy Organic Trace Compounds in Synthesis Gas." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-277054.
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There currently exists no commercialized method for rapid sampling and analysis of trace tar ingas streams. Solid phase microextraction (SPME) with a polydimethylsiloxane (PDMS) solidphase has been previously investigated as a possible candidate due to its solvent-free natureand reusability. This project set out to deliver a proof of concept study to test whether SPMEcan be sufficiently tuned to analyse trace tar content in syngas below the concentration of 0.1mg/Nm 3 . Due to complications that arose from the Covid-19 pandemic, it was unfeasible tocarry out the practical elements of the project. Instead a concept design for carrying out such astudy has been successfully developed. This design envisions a two-chamber setup able tosample syngas directly from a gasifier at 60 °C and 125 °C respectively and is illustrated in thetext. It utilizes commercially available solvent tubes to cross-check and verify the SPME results.I nuläget finns det ingen kommersiell metod för att snabbt extrahera och analysera spår av tjärkomponenteri gasströmmar. Tidigare har solid phase microextraction (SPME) medpolydimetylsiloxan (PDMS) som fast fas undersökts som en möjlig kandidat då den ej kräverlösningsmedel och kan enkelt återanvändas. Detta projekt hade som mål att bevisa att SPMEkan anpassas tillräckligt känsligt för att analysera spår av tjära i syngas med en koncentration påmindre än 0,1 mg/Nm 3 . På grund av komplikationer som uppstod i samband med Covid-19pandemin var det inte möjligt att utföra den praktiska delen av projektet. Istället så har endesign tagits fram för ett koncept som beskriver hur man kan genomföra den praktiska delen.Designen beskriver en två-kammare lösning som kan användas för att ta prover från syngas somkommer direkt från en förgasare. Proverna tas vid temperaturer om 60 °C och 125 °C för attuppnå maximal känslighet. En uppsättning kommersiellt tillgängliga sorbentrör används för attkontrollera resultaten från SPME.
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Fitzpatrick, Daniel Ewert. "Engineering chemistry : integrated control strategies and Internet-enabled tools for chemical synthesis." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267427.
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The use of enabling technologies and continuous methods to enhance chemical synthesis is a vibrant area of research, gaining increasing attention from laboratories in academia and industry. Yet many prominent synthesis procedures have not changed for decades and require significant manual intervention from bench chemists, which may lead to the waste of both human and material resources. The research described herein details how chemistry has been bridged with engineering to address this issue in a world increasingly focussed on sustainability and efficiency. This thesis is divided into four chapters. The first describes the development of a novel Internet-based process control system which is applied to automate a cycling catalytic process. The capability of the system to conduct multi-dimensional self-optimisation processes is shown, where it is integrated with an on-line mass spectrometer and inline infrared spectrometer to drive optimisation against customisable multicomponent evaluation functions. Chapter 2 details the successful synthesis of the anti-cancer drug candidate AZ82. The control system is applied to assist with a number of these steps, including facilitating the integration between batch and flow processes on a single reactor platform. A new distillation unit to assist with downstream solvent switching is also described. In Chapter 3, the cloud-based nature of the control system is exploited by moving it to servers residing in Tokyo. The ability of the system to accelerate the drug development process is highlighted with the autonomous self-optimisation and synthesis of four active pharmaceutical ingredient targets: tramadol, lidocaine, bupropion and isoniazid. In the case of bupropion, the system maintained steady-state operation of a telescoped two-step process for an extended period. A researcher in Los Angeles was able to initiate and monitor all processes, via Japan, in real-time as they occurred in our laboratory in Cambridge, UK. Finally, Chapter 4 describes the development of a new parallel column supercritical fluid chromatography (SFC) unit that is capable of separating a multicomponent product stream continuously exiting a flow reactor. The versatility of the SFC unit is showcased with the telescoped synthesis of isoniazid in which all stages, including the SFC process itself, are managed by the control system without researcher intervention.
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Hay, Duncan A. "Design and synthesis of small molecule chemical probes for bromodomain-containing proteins." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:04f6c56d-72de-4c32-b0fd-cc4bcdc996a8.
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Bromodomains (BRDs) are protein modules which bind to acetylated lysines on histones and transcriptional regulating proteins. BRD-containing proteins are involved in a large variety of critical cellular processes and their misregulation, or mutation of the genes encoding for them, has been linked to pathogenesis in humans. The generation of chemical probes (potent, selective and cell permeable small molecules) in cellular experiments to investigate the biological role of the BRDs is thus desirable. A chemical probe for the CREB (cyclic-AMP response element binding protein) binding-protein (CBP) and E1A binding protein (p300) BRDs was developed, starting from a low molecular weight, weak and non-selective dimethylisoxazole benzimidazole compound. Parallel synthesis was used to optimise the initial hit into a weak, but selective CBP inhibitor. Further modification of the two N-1 and C-2 moieties of the benzimidazole scaffold, led to highly potent and selective CBP inhibitors. Structure-guided design was then applied to optimise the selectivity of the series for CBP over the first domain of bromodomain-containing protein 4 BRD4(1). A strategy to reduce the flexibility of the N-1 and C-2 ethylene linker groups through the incorporation of conformational constraints led to inhibitors with increased selectivity. The optimal compound was highly potent for the CBP and p300 BRDs (Kd 21 nM and 32 nM, respectively) and selective over BRD4(1) (40-fold and 27-fold, respectively). On-target cellular activity was observed in a fluorescence recovery after photobleaching (FRAP) assay (0.1 μM), a p53 reporter gene assay (IC50 1.5 μM) and a Förster resonance energy transfer (FRET) assay (5 μM). A weak indolizine bromodomain-containing protein 9 (BRD9) inhibitor was used as the starting point for the development of a BRD9/BRD7 chemical probe. Analogues were synthesised via [3+2] cycloadditions. An optimised compound was found to be highly potent (68 nM) and selective over BRD4(1) (34-fold). On-target cellular activity was observed in a FRAP assay (5 μM). Efforts were made to improve the cellular activity through the introduction of an ionisable centre to aid solubility. A selection of piperazine analogues were shown to be potent and selective, and these compounds warrant further investigation of their selectivity and cellular activity. Overall, the work has led to the first potent and selective inhibitors of the CBP/p300 and BRD9 BRDs. It also highlights the role of structural analysis in the development of inhibitors that modulate protein-protein interactions.
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Liao, Xiangjun 1970. "Dielectric properties and their application in microwave-assisted organic chemical reactions." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38220.
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This study was designed to develop some predictive models for the dielectric properties of the chemicals and chemical reactions and make use of dielectric properties and microwave irradiation in the chemical reactions. Specifically, the dielectric properties of the following systems were investigated at microwave frequencies of 2450 and 915 MHz: (1) C1--C5 alcohols, (2) glucose aqueous solutions, (3) lysine aqueous solutions, (4) mimicked esterification reaction model systems of parahydroxybenzoic acid with methanol, 1-propanol and 1-butanol in the presence of para-toluene sulfonic acid as a catalyst, (5) Maillard reaction model system consisting of glucose, lysine and water.The dielectric properties of the model systems showed that they depended on the frequency applied, concentration of the material, and temperature. Most of the predictive models showed that there exists a linear or quadratic relationship between dielectric constant and concentration or temperature. However, the quadratic equation is better than the linear one to describe the variation of the loss factor with temperature or concentration.
Esterification showed great advantages for the use of microwave irradiation in chemical reaction. It included reduction in reaction time, and provided distinct temperature profiles due to microwave environment during chemical reactions. The reason for rate enhancement of this type of reaction was also demonstrated from the temperature profile.
Microwave-assisted solvent free Maillard reaction model system, consisting of glucose and lysine, demonstrated that the heating method applied was not one of the crucial factors, but the temperature level was important during the chemical reaction.
The relationship of loss factor with yield of reaction showed that it is possible to use dielectric data to analyze, and monitor the chemical reaction. It provided a new methodology to analyze the reaction.
The relationship between the loss factor, loss tangent and the reaction time, and concentration of the material showed that it is also possible to use dielectric data at microwave frequencies of 2450 and 915 MHz to study chemical reactions, especially the kinetics.
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Lobb, Kevin Alan. "Camphor derivatives in asymmetric synthesis: a synthetic, mechanistic and theoretical study." Thesis, Rhodes University, 2008. http://hdl.handle.net/10962/d1006770.
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A series of 3,3-ethylenedioxy-exo- and endo- bornyl esters have been prepared and subjected to α-benzylation using lithium diisopropylamide and benzyl bromide. In the exo-series of esters the diastereofacial selectivity of benzylation was found to improve (up to 34% d.e.) as the steric bulk of the O-alkyl group increased, whereas in the endo-series, a surprising decrease in stereoselectivity was observed as the steric bulk increased – an observation attributed to flexibility of the metal-coordinated endo-enolate system, compared to the relative rigidity of the exo analogues. The conformational options for each series was explored at the density functional theory level. Reductive cyclization of a range of specially prepared N-carbobenzyloxy-amino acid esters has been shown to afford the corresponding derivatives, contrary to previous reports that the cyclization is limited to the glycine derivative. The cyclization sequence has been explored in detail, and the yield has been shown to be critically dependent on the stereochemistry of the α-amino acid moiety. Moreover, it seems that reductive cyclization occurs more readily with the endo- rather than the exo-bornyl N-CBZ-amino acid esters. Molecular modelling of relevant transition states at the DFT levels indicates that L-amino acid-derived systems should cyclize preferably in the exo-series and D-amino acid-derived systems should cyclize preferably in the endo series. Studies of alkylation of an iminolactone system have reported an interesting anomaly - exo-methylation is observed while endo-alkylation predominates for larger alkyl groups. This has been studied in detail at the DFT level, and the anomaly is attributed to thermodynamic control in the methyl case, whereas kinetic control is the norm in this system. Preliminary computer modelling of the intramolecular rearrangement of a 3,3-xylylbornyl system at the HF/STO-3G level raised doubts concerning the structure assigned by Evans to one of the rearrangement products, prompting an X-ray crystallographic analysis and leading to the revision of its structure from a pinene to a camphene derivative. The previously elusive spiro[bornane-3,2’-indan]-2-exo-tosylate has been successfully isolated, and the kinetics of its ready decomposition to the two camphene products has been followed by 1H NMR spectroscopy. The endo-tosylate analogue, on the other hand, was found to be remarkably stable. Kinetic data obtained for rearrangement of this exo-bornyl tosylate have indicated the operation of tandem autocatalytic and pseudo-first-order transformations leading sequentially to the two isomeric camphene products. An extensive coset analysis of all possible rearrangement processes of the initially-formed cation formed from decomposition of the exo-tosylate has afforded a graph containing 336 classical cations (modelled at the AM1 and B3LYP levels) and 526 transition-state complexes (modelled at the AM1 level). This analysis afforded a viable 4-step classical mechanism connecting the first camphene product with the second. A more realistic study, involving non-classical carbocations, has afforded a graph of all possible (classical and non-classical) cations that could be formed by rearrangment of the initiallyformed cation. The resulting graph confirms that the only energetically feasible path corresponds to the classical mechanism, but simply involves two steps, including a novel, concerted Wagner-Meerwein – 6,2-hydride shift – Wagner-Meerwein rearrangement.
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Matthews, Jason Shastri. "Design and synthesis of volatile compounds for chemical vapor deposition of electronic materials." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/30487.
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Mehdizadeh, Ali. "A mechanistic study of the reactions of geminal dihalides with lithium diisopropylamide (LDA)." Thesis, Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/27172.
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Crews, Everett III. "Retroaldo-trapping reactions of [beta]-hydroxy-[alpha]-phenylsulfenyl cyclohexanone and decalone derivatives and the total synthesis of the California red scale sex pheromone." Diss., Georgia Institute of Technology, 1985. http://hdl.handle.net/1853/27404.
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Sproule, Kenneth. "Microbial production of an aromatic cis-1,2-dihydrodiol and its application in chemical synthesis." Thesis, University of Warwick, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334161.
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Dominique, Romyr. "Application of olefin metathesis reaction towards the synthesis of oligosaccharide mimics: A novel strategy in chemical glycobiology." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/28952.
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Glycobiology has gained a lot of interest in the scientific community in the past few years. It is now well established that the oligosaccharides on cell surfaces are involved in key recognition processes. However, the determination of oligosaccharide sequence on a specific glycoconjugate and their chemical synthesis are still far from routine. Herein, we report a new strategy in chemical glycobiology making use of olefin metathesis reaction as a powerful chemical tool towards the synthesis of oligosaccharide mimics. This strategy allows the synthesis of multivalent molecules that could help to understand and control events mediated by oligosaccharides. A glycomimetic approach to the branched trimannoside 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside will also be described.
The synthesis of carbohydrate homodimers was accomplished by self metathesis of O- and C-alkenyl glycosides using 10 mol% of Grubbs' catalyst bis (tricyclohexylphosphine) benzylidene ruthenium (IV) dichloride, [(PCy3)2RuCl2 = CHPh]. The reaction is high yielding, compatible with different protecting groups and the length of the linker can be easily changed. A mixture of stereoisomers was obtained in which the E isomer was major. Once deprotected, these homodimers can be viewed as chemical inducers of dimerization therefore the hypothesis that they can induce signal transduction was suggested.
Extension of O- and C-alkenyl glycosides was also achieved by cross-metathesis reaction using Grubbs' catalyst. Extended alkenyl glycosides with reactive functional groups were obtained in high yield and good stereoselectivity. The utilization of 2--4 equiv. of alkenes and 20 mol % of catalyst were sufficient to favor the formation of the cross-metathesis products. A novel C-linked (1-6)-pseudodisaccharide could be synthesized using this procedure.
A sequence of olefin metathesis and Sharpless asymmetric dihydroxylation reactions were used to create a novel class of glycoclusters having varied structural and stereochemical environments. Well-defined tri- and tetra-valent mannoside-based glycoclusters were thus prepared.
Another application of olefin metathesis reaction was found in the synthesis of a trimannoside ligand toward human Mannose-binding protein which plays an important role in the innate immunity. To further understand its role, the design of high affinity ligands was attempted. Preliminary biological results showed improved inhibitory potentials.
Finally, two generation of glycomimetics of 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, the natural ligand recognized by legume lectin, concanavalin A were synthesized. Thus, highly substituted C-aryl mannoside, as well as O, N, C-linked 1,2,3-triazole mannosides were prepared.
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Samra, Babinder Kaur. "The use of enzyme catalysts in organic media for the synthesis of biodegradable polyesters." Thesis, Aston University, 1996. http://publications.aston.ac.uk/9771/.
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The enzyme catalysed polytransesterification of diesters with diols was investigated under various conditions. The most consistent results were obtained using crude porcine pancreatic lipase (PPL) suspended in anhydrous diethyl ether. Addition of molecular sieve to the above system gave higher molecular weight products. The PPL catalysed reaction of bis(2,2,2-trichlorethyl) adipate and glutarate with butane-1,4-diol in anhydrous ether with and without molecular sieve was investigated over a range of times from 8 to 240 hours. The 72 hour adipate reaction with molecular sieve gave the highest molecular weight polymer (Mn 6,500 and Mw 9,400). The glutarate gave the maximum molecular weight polyester after 24 hours (Mn 5,700 and Mw 9,500). Occasionally the glutarate reaction produced very high molecular weight polyester-enzyme complexes. Toluene generally gave lower molecular weight products than diethyl ether. Dichloromethane and tetrahydrofuran gave mainly dimers and trimers. Alternative enzyme and diol systems were also investigated. These yielded no polymeric products. The molecular weights of the polyesters were determined by 1H NMR end-group analysis and by GPC. The molecular weights determined by NMR were on average about twice as great as those determined by GPC. The synthesis of the following diesters is described: i)Bis(2,2,2-trichloroethyl) succinate, glutarate, adipate, trans-3-hexenedioate, and trans-3,4-epoxyadipate. ii) Diphenyl glutarate and adipate. iii)Bis(2,2,2-fluoroethyl) glutarate and trans-3-hexendioate. iv) Divinyl glutarate. v) N,N'Glutaryl dicyclohexanone oxime. The polytransesterification of all the above esters with diols was investigated. The easily synthesised bis(2,2,2-trichloroethyl) glutarate and adipate gave the best results and the work was concentrated on these two esters.
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Ndi, Cornelius Ndi. "Synthesis of Chemical Models of Hydrolase Enzymes for Intramolecular Catalysis." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etd/1356.
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Most nuclease enzymes can hydrolyze phosphoester bonds (in DNA and RNA) by using metal ions cofactors that coordinate and activate water molecules in the enzymes' active sites. However, there are some hydrolase enzymes (including nucleases) that can function without the aid of metal ions. 2,6-Di(1H-imidazol-2-yl)phenol, a model compound for hydrolase enzyme, was synthesized by the reaction between ethylenediamine and dimethyl-3-carboxysalicylate, initially resulting in the formation of diimidazoline. The diimidazoline was subsequently aromatized to the diimidazole by dehydrogenation over palladium. The overall reaction yield was low; therefore, other dehydrogenation transformation reactions were tried but all failed to improve the yield. Converting this diimidazolphenol into diimidazolphenyl monophoshpate derivative was attempted but failed to give desired products.
Synthesis of 2,2'-anthracene-1,8-diylbis-1H-imidazole, another model compound for hydrolase enzymes, was attempted using dimethyl-1,8-anthracenedicarboxylate, but synthesis was unsuccessful due to solubility problem.
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楊小雯 and Siu-man Yeung. "The synthesis and reactions of 3H-pyrroles bearing methyl and aryl groups." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1991. http://hub.hku.hk/bib/B31210119.
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Vargas, Morales Juan Manuel. "Towards a low temperature synthesis of graphene with small organic molecule precursors." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/50278.
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Graphene, a 2D honeycomb lattice of sp² hybridized carbons, has attracted the attention of the scientific community not only for its interesting theoretical properties but also for its myriad of possible applications. The discovery of graphene led to the Nobel Prize in physics for 2010 to be awarded to Andrei Geim and Konstantin Novoselov.
Since its discovery, many methods have been developed for the synthesis of this material. Two of those methods stand out for the growth of high quality and large area graphene sheets, namely, epitaxial growth from silicon carbide (SiC) and chemical vapor deposition (CVD). As it stands today, both methods make use of high concentrations of hydrogen (10-20%) in N₂ or Ar, high temperatures, and a vacuum system. Epitaxial growth from SiC in addition requires very expensive single crystal SiC wafers. In the case of CVD, organic molecules are used as the carbon source to grow graphene on a metal substrate. Although graphene has been grown on many metal substrates, the experiments highlighted here make use of copper as the metal substrate of choice since it offers the advantage of availability, low price, and, most importantly, because this substrate is self-limiting in other words, it mostly grows single layer graphene. Because the CVD method provides with a choice as for the carbon source to use, the following question arises: can a molecule, either commercially available or synthesized, be used as a carbon source that would allow for the synthesis of graphene under low temperatures, low concentrations of hydrogen and at atmospheric pressure?
This dissertation focuses on the synthesis of graphene at lower temperatures by using carbon sources with characteristics that might make this possible. It also focuses on the use of forming gas (3% H₂ and 97% N₂ or Ar) in order to make the overall process a lot safer and cost effective. This dissertation contains two chapters on the synthesis of organic molecules of interest, and observations about their reactivity are included.
CVD experiments were performed at atmospheric pressure, and under vacuum. In both instances forming gas was used as the annealing and carrier gas. Results from CVD at atmospheric pressure (CVDAP), using organic solvents as carbon sources, show that at 1000℃, low quality graphene was obtained. On the other hand, CVD experiments using a vacuum in the range of 25 mTorr to 1 Torr successfully produced good quality graphene. For graphene growth under vacuum conditions, commercially available and synthesized compounds were used. Attempts at growing graphene at 600℃ from the same carbon sources only formed amorphous carbon. These results point to the fact that good quality graphene can basically be grown from any carbonaceous material as long as the growth temperature is 1000℃ and the system is under vacuum.
In addition to the synthesis of graphene at low temperatures, there is a great amount of interest on the synthesis of graphene nanoribbons (GNR’s) and, as with graphene, several approaches to their synthesis have been developed. One such method is the synthesis of GNRs encapsulated in carbon nanotubes. Experiments were conducted in which aluminosilicate nanotubes were used. These nanotubes provided for an easier interpretation of the Raman spectrum since the signals from the nanotubes do not interfere with those of the GNR’s as in the case when carbon nanotubes are used. The use of aluminosilicate nanotubes also allowed for the successful synthesis of GNR’s at temperatures as low as 200℃ when perylene was used as the carbon source.
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Ye, Yulin. "Design and synthesis of myo-inositol (1,4,5)-trisphosphate receptor antagonists : design and synthesis of IP3 receptor antagonists." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:5e75b5e0-d42a-4b58-9c46-7fabff99e10e.
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Well-regulated Ca2+ signalling is essential for every living organism, and disruption of this signalling can lead to diseases including heart failure, neurological disorders and diabetes. Intracellular Ca2+ levels are regulated by influx of extracellular Ca2+ through channels located in the cell membrane. In addition, release of Ca2+ from intracellular stores also plays an important role in controlling intracellular Ca2+ concentration. Of the three types of intracellular Ca2+ stores that have been characterised those with D-myo-Inositol 1,4,5 trisphosphate receptors (InsP3Rs) showed a close relationship with cell proliferation. Hence, selective blockage of InsP3Rs will allow better understanding of Ca2+ signalling and might also unveil novel treatment for cancers, in the long term. There were no selective InsP3Rs antagonists known at the start of these studies. Based on the crystal structure of InsP3Rs bound to InsP3 and SAR studies of InsP3, we designed and tested several InsP3 analogues.1 Compound 15, 16 and 23 acted as InsP3R antagonists, though their selectivity for InsP3Rs was not completely determined. Furthermore, we also attempted to improve the potency of 16 via substitution at the 1-postion phosphate. By considering the interaction formed between adenophosphostins and InsP3Rs compounds (53-55) were designed and synthesised. In addition, analogues of compound 92, selected from an in silico screen, have led to the discovery of another novel scaffold that acts as an InsP3R antagonist.
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Learmonth, Robin Alec. "Studies in asymmetric synthesis." Thesis, Rhodes University, 1991. http://hdl.handle.net/10962/d1005018.
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The concept of combining two well established areas of organic chemistry, viz., organosilicon chemistry and the use of chiral auxiliaries, into a viable, alternative method of asymmetric synthesis has only very recently begun to receive attention. At the outset of this investigation, no asymmetric reactions of silyl enol ethers, chiral by virtue of optically active substituents on the silicon, had been reported. A range of novel chiral silyl enol ethers have thus been prepared from a variety of ketones, including pinacolone, cyclohexanone, and α-tetralone, and employing menthol, borneol, and cholesterol as chiral auxiliaries. These preparations have been achieved via several distinct routes, including a novel convergent approach involving the isolation of either the chloro(menthyloxy)dimethylsilane or the (bornyloxy)chlorodimethylsilane. The MS and NMR spectra of these silyl enol ethers were examined in detail and, in the case of the crystalline cholesteryloxy silyl enol ether, the X-ray structure has been determined. The potential of chloroalkoxysilanes to act as general, chiral derivatizing agents has been established by the preparation of diastereomeric silyl acetal mixtures of racemic secondary alcohols (e.g. I-phenylethanol and 2-octanol). The experimental diastereomeric ratios, obtained by GLC and ¹H NMR spectroscopy, approached the expected value of unity, confirming the potential of the alkoxychlorosilanes as chiral probes. The chiral silyl enol ethers have been successfully oxidized to the corresponding α-siloxy ketones employing MCPBA, MMPP, and 2-(phenylsulphonyl)-3-phenyloxaziridine as oxidizing agents and the diastereomeric excesses obtained, which varied from 0 to 16%, indicated some potential for stereochemical control. Alkylation and hydroxyalkylation reactions of the silyl enol ethers have yielded the expected α-iert-butyl and β-hydroxy ketones in good to excellent material yields, with the enantiomeric excesses, as determined by chiral shift reagent studies, reaching 14%. To improve the stereo control in these reactions, attempts have been made to prepare chiral silyl enol ethers with auxiliaries possessing the potential for transition state complex co-ordination in the reactions under consideration. The preparation of such silyl enol ethers, incorporating the proline-derived auxiliaries, N-methyl-2-hydroxymethylpyrrolidine and 2-methoxymethylpyrrolidine met with only limited success. In an alternative approach, three derivatives of 2,3-dihydroxybornane have been prepared. However, two of these auxiliaries, viz., 3-exo-benzyloxy-2-exo-hydroxybornane and 3-exo-(1-methoxyethoxy)-2-exo-hydroxybornane failed to form silyl enol ethers, even under considerably more vigorous conditions than normally employed. The third derivative, 3,3-ethylenedioxy-2-hydroxybornane has been successfully utilized in the preparation of a pinacolone-derived chiral silyl enol ether. Hydroxyalkylation of this compound with benzaldehyde has yielded the β-hydroxyketone with significantly improved enantiomeric excess (26%) and a transition state complex has been proposed to rationalize this improvement.
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Hagberg, Daniel. "Synthesis of Organic Chromophores for Dye Sensitized Solar Cells." Doctoral thesis, KTH, Organisk kemi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-10547.
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This thesis deals with development and synthesis of organic chromophores for dye sensitized solar cells. The chromophores are divided into three components; donor, linker and acceptor. The development of efficient organic chromophores for dye sensitized solar cells starts off with one new organic chromophore, D5. This chromophore consists of a triphenylamine moiety as an electron donor, a conjugated linker with a thiophene moiety and cyanoacrylic acid as an electron acceptor and anchoring group. Alternating the donor, linker or acceptor moieties independently, would give us the tool to tune the HOMO and LUMO energy levels of the chromophores. The following parts of this thesis regard this development strategy. The contributions to the HOMO and LUMO energy levels were investigated when alternating the linker moiety. Unexpected effects of the solar cell performances when increasing the linker length were revealed, however. In addition, the effect of an alternative acceptor group, rhodanine-3-acetic acid, in combination with different linker lengths was investigated. The HOMO and LUMO energy level tuning was once again successful. Electron recombination from the semiconductor to the electrolyte is probably the cause of the poor efficiencies obtained for this series of dyes. Finally, the development of functionalized triphenylamine based donors and the contributions from different substituents to the HOMO and LUMO energy levels and as insulating layers were investigated. This strategy has so far been the most successful in terms of reaching high efficiencies in the solar cell. A top overall efficiency of 7.79 % was achieved.QC 20100716
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Cho, Joungmo. "Computational studies of reacting flows with applications in nanoscale materials synthesis." Amherst, Mass. : University of Massachusetts Amherst, 2009. http://scholarworks.umass.edu/dissertations/AAI3372259/.
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