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Turner, Richard Vernon. "SYNTHETIC CANNABINOIDS: CHARACTERIZING THEIR USE AND CESSATION." OpenSIUC, 2019. https://opensiuc.lib.siu.edu/dissertations/1766.
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Since their introduction to the United States in 2008, synthetic cannabinoids became the most widely used recreational drug behind marijuana, then regressed to an estimated prevalence of less than 1%. Contrary to expectations for a drug declining in use, emergency department presentations and acute poisonings related to the use of synthetic cannabinoids are increasing. Alongside this phenomenon, a growing body of literature is beginning to uncover a relationship between psychosis and synthetic cannabinoid use. A current gap in the literature exists surrounding harm prevention methods and targeted intervention strategies for users of synthetic cannabinoids. To date, no known studies have examined individuals with a history of use of these substances and investigated the reasons they decided to discontinue recreational use. The purpose of the current study was to fill this gap in the literature while also further confirming and expanding existing research on the characterization of synthetic substance use, perceived harm of synthetic cannabinoids, and users’ knowledge about synthetic cannabinoids. Cross sectional survey methods in a non-experimental comparative design was utilized with participants recruited through the online crowd sourcing platform Amazon MTurk. Significant motivating factors for both discontinuation and continuation of synthetic cannabinoid use were found including personal experience, accessibility, preference towards other substance, and questions surrounding the source and purity of the synthetic cannabinoids. It was also found that individuals who currently use synthetic cannabinoids have less general knowledge about the substance class when compared to individuals who have discontinued use. These results suggest that psychoeducational campaigning surrounding general knowledge about the substance class as well as information on the physiological effects of synthetic cannabinoids may be an effective harm reduction method.
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Costa, Lia Filipa Alvarez Pereira da Mota e. "Cannabinoids impact on pregnancy: effects in trophoblast cells." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15948.
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Mestrado em Biologia Molecular e CelularCannabinoids (CBs) can be classified as: phytocannabinoids, the constituents of the Cannabis sativa plant; synthetic cannabinoids lab-synthesized and the endocannabinoids that are endogenous lipid mediators. Cannabinoid compounds activate cannabinoid receptors – CB1 and CB2. The most prevalent psychoactive phytocannabinoid is Δ9tetrahydrocannabinol (THC), but more than 60 different CBs were already identified in the plant. The best characterized endocannabinoids (eCBs) are anandamide (AEA) and 2arachidonoylglycerol (2-AG), that are involved in several physiological processes including synaptic plasticity, pain modulation, energy homeostasis and reproduction. On the other hand, some synthetic cannabinoids that were initially designed for medical research, are now used as drugs of abuse. During the period of placental development, highly dynamic processes of remodeling occur, involving proliferation, apoptosis, differentiation and invasion of trophoblasts. It is known that a tight control of eCBs levels is required for normal pregnancy progression and that eCBs are involved in trophoblast cells turnover. Therefore, by sharing activation of the same receptors, exposure to exocannabinoids either by recreational or medicinal use may lead to alterations in the eCBs levels and in the endocannabinoid system homeostasis In this work, it was studied the impact of CBs in BeWo trophoblastic cells and in primary cultures of human cytotrophoblasts. Cells were treated for 24 hours with different concentrations of THC, the synthetic cannabinoid WIN‐55,212 (WIN) and 2-AG. Treatment with THC did not affect BeWo cells viability while WIN and 2-AG caused a dose-dependent viability loss. Morphological studies together with biochemical markers indicate that 2-AG is able to induce apoptosis in cytotrophoblasts. On the other hand, morphological studies after acridine orange staining suggest that autophagy may take part in WIN-induced loss of cell viability. All cannabinoids caused a decrease in mitochondrial membrane potential (Δψm) but only 2-AG led to ROS/RNS generation, though no changes in glutathione levels were observed. In addition, ER-stress may be involved in the 2-AG induced-oxidative stress, as preliminary results point to an increase in CCAAT-enhancer-binding protein homologous protein (CHOP) expression. Besides the decrease in cell viability, alterations in cell cycle progression were observed. WIN treatment induced a cell cycle arrest in G0/G1 phase, whereas 2-AG induced a cell cycle arrest in G2/M phase. Here it is reinforced the relevance of cannabinoid signaling in fundamental processes of cell proliferation and cell death in trophoblast cells. Since cannabis-based drugs are the most consumed illicit drugs worldwide and some of the most consumed recreational drugs by pregnant women, this study may contribute to the understanding of the impact of such substances in human reproduction.
Os canabinóides (CBs) podem ser classificados como: fitocanabinóides, os constituintes da planta Cannabis sativa L.; canabinóides sintéticos, sintetizados em laboratório e os endocanabinóides, que são mediadores lipídicos endógenos. Os compostos canabinóides ativam recetores canabinóides – CB1 e CB2. O composto psicoativo mais prevalente é o Δ9-tetrahidrocanabinol (THC), mas mais de 60 diferentes CBs foram já identificados a partir da planta. Os endocanabinóides (eCBs) melhor caracterizados são a anandamida (AEA) e o 2-araquidonoilglicerol (2-AG), que estão envolvidos em vários processos biológicos, incluindo plasticidade sináptica, modulação da dor, homeostasia energética e reprodução. Por outro lado, alguns canabinóides sintéticos, inicialmente projetados para investigação médica, são agora usados como drogas de abuso. Durante o período de desenvolvimento placentário ocorrem processos de remodelação que envolvem proliferação, apoptose, diferenciação e invasão dos trofoblastos. Sabe-se que um controlo rigoroso dos níveis de eCBs é necessário para uma progressão normal da gravidez e que os eCBs estão envolvidos no turnover celular dos trofoblastos. Assim sendo, ao partilharem a ativação dos mesmos recetores, a exposição a exocanabinóides, seja pelo uso recreativo ou medicinal, pode levar a alterações nos níveis de eCBs e na homeostasia do sistema endocanabinóide (ECS). Neste trabalho foi estudado o impacto dos CBs em células trofoblásticas BeWo e em culturas primárias de citotrofoblastos humanos. As células foram tratadas durante 24 horas com diferentes concentrações de THC, do canabinóide sintético WIN-55,212 (WIN) e de 2AG. O tratamento com THC não afetou a viabilidade das células BeWo, enquanto que o WIN e o 2-AG causaram uma perda de viabilidade dependente da dose. Estudos morfológicos, juntamente com marcadores bioquímicos, indicam que o 2-AG é capaz de induzir apoptose em citotrofoblastos. Por outro lado, estudos morfológicos realizados com laranja de acridina sugerem que a autofagia pode estar envolvida na perda de viabilidade induzida pelo WIN. Todos os canabinóides induziram perda de potencial de membrana mitocondrial (Δψm), mas apenas o 2-AG levou a um aumento na formação de ROS/RNS, sem terem sido observadas diferenças nos níveis de glutationa. O stress reticular pode estar envolvido no stress oxidativo induzido pelo 2-AG, visto que resultados preliminares apontam para um aumento na expressão de CCAAT-enhancer-binding protein homologous protein (CHOP). Para além da diminuição da viabilidade celular, os resultados sugerem alterações na progressão do ciclo celular. O tratamento com WIN induziu retenção do ciclo celular em fase G0/G1, enquanto que o 2-AG levou a uma retenção em fase G2/M. Neste trabalho é reforçada a importância da sinalização canabinóide em processos importantes de proliferação e morte celular de células trofoblásticas. Visto que as drogas canabinóides são as mais consumidas a nível mundial, e umas das drogas recreativas mais consumidas pelas mulheres grávidas, este estudo pode contribuir para a compreensão do impacto destas substâncias na reprodução humana.
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Wang, Pu. "Synthetic studies on natural products." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/13199.
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This thesis consists of three relative independent projects all of which concentrate on the syntheses of biologically active natural products. In the first project, a convenience route for synthesis of [8-3H]-berberine sulfate has been established and two routes for preparation of 14C labelled berberine are explored. A series of compounds containing a methylenedioxyphenyl functionality have been synthesised for using as antigens in immunological studies. The second project concerns development of chemistry directed towards the stereocontrolled synthesis of Baogongteng A, a novel 2,6-disubstituted tropane alkaloid which is a powerful M-cholinergic agonist used in the treatment of glaucoma. By exploiting 4-hydroxy-L-proline as the chiral synthon, useful methods such as preparation of 2-formyl 4-hydroxy-L-proline derivatives, and the stereoselective bromination of the C-3 of 4-hydroxy-L-proline derivatives, have been established. About forty new organic compounds have been synthesised and identified. The final project concerns exploration of new routes for the syntheses of biotin biosynthetic precursors and their fluorined analogues which are types of compounds potentially valuable in agricultural chemistry. This work has led to the development of methods of wide application, such as the preparation of highly purified N-Boc-L-alaninal, which should prove to be of use in future studies in this and related fields.
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Stephens, Jason L. "Synthetic Cannabinoid Usage among College Students: The Example of K2 and Spice." Thesis, University of North Texas, 2011. https://digital.library.unt.edu/ark:/67531/metadc84283/.
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The primary goal of this study was to investigate the awareness and prevalence of Spice and K2 usage among a population of college students, as well as the demographics of such users. The study also sought to determine whether or not students prefer these products over natural cannabis, in addition to examining the most popular methods of obtainment and the most commonly reported side effects of K2 and Spice usage. Participants consisted of 643 undergraduate students enrolled at the University of North Texas during the fall 2011 semester. Findings indicate that while students exhibit a relatively high awareness of K2 and Spice, usage of these products is not a prevalent occurrence. Implications of the findings are discussed.
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Jin, Changdong. "Natural antifungals and their synthetic analogues." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0013/NQ59979.pdf.
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Pfeiffer, Matthew W. B. "Synthetic studies on cyathane natural products." Diss., Connect to online resource, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3219217.
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Liu, Yunqi. "Synthetic approaches toward natural product synthesis." Diss., The University of Arizona, 1995. http://hdl.handle.net/10150/187050.
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1,2-Dithiolan-3-one-1-oxide exists in antihumor antibiotic leinamycin and can cause DNA cleavage in the presence of thiols. Diastereoselective synthesis of this unique ring system has been achieved by low temperature oxidation of the corresponding 1,2-dithiolan-3-ones with 3,3-dimethyldioxirane. 5-Methyl-1,2-dithiolan-3-one-1-oxides were synthesized by oxidation of 5-methyl-1,2-dithiolan-3-one with 3,3-dimethyldioxirane. Eu(fod)₃ and C₆D₆ induced proton chemical shift studies showed that the major isomer in the product has a trans sulfoxide relative to the 5-methyl group. Low temperature oxidation of 4-substituted-amino-5,5-dimethyl-1,2-dithiolan-3-ones by 3,3-dimethyldioxirane preferentially led to the corresponding trans-1,2-dithiolan-3-one-1-oxides. This assignment was made on the basis of a X-ray crystallographic structure study. Formation of azlactones as well as 1,2-dithiolan-3-one-1,1-dioxide were also observed when some substituted 1,2-dithiolan-3-ones were oxidized by 3,3-ditnethyldioxirane. Three 2,2-dimethyl-1,3-dithian-4-ones were synthesized by SnCl₄ mediated condensation of β-mercaptothioacids and acetone. Oxidation of 2,2,6-trimethyl-1,3-dithian-4-one with Ce(IV) did not give 1,2-dithiolan-3-one or 1,2-dithiolan-3-one-1-oxides as anticipated; 1,3-dithian-5-en-4-one was detected as the product instead. Synthetic approaches toward loline were explored. Intramolecular photoaddition of bicyclic olefinic N-nitrosamine did not give the desired product. An epoxide approach did not furnish loline due to unsuccessful epoxide ring opening by azide ion. In the urea approach, the tertiary nitrogen of the bicyclic urea preferentially undergoes a transannular iodocyclization. The same results were obtained by halocyclizing bis-silylimidate or mono-silylimidate of the bicyclic urea.
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Belfort, Georges. "Diffusion in synthetic and natural membranes." Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-184597.
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Thornhill, Andrew John. "Synthetic studies towards marine natural products." Thesis, Bangor University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364987.
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Xiong, Xin. "Synthetic approaches towards heterocyclic natural producers." Thesis, Cardiff University, 2005. http://orca.cf.ac.uk/55520/.
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A variety of tri- and tetrasubstituted pyridines are prepared by new one-pot processes, developed by modification and improvement of the traditional Bohlmann-Rahtz reaction. The use of zinc(II) bromide catalysis, microwave irradiation and conductive heating in a sealed tube is described to facilitate rapid Michael addition-cyclodehydration of an enamine and alkynone in a single synthetic step and with total control of regiochemistry. Expanding the Bohlmann-Rahtz heteroannulation reaction leads to the development of a mild one-pot three-component syntheses of pyridines, a tandem oxidation-heteroannulation process for one-pot synthesis of pyridines from propargylic alcohols, a highly facile combined three-component tandem oxidation-heteroannulation process and a novel tetrasubstituted bromopyridine synthesis mediated by N-bromosuccinimide. The synthesis of dimethyl sulfomycinamate (13), the acidic methanolysis product of the sulfomycin family of thiopeptide antibiotics, from methyl-4-(trimethylsilyl-2-oxobut-3-ynoate (216) is achieved in 13 steps by the Bohlmann-Rahtz heteroannulation of 1-(oxazol-4-yl)enamine 252 or in 12 steps and 9% overall yield by three-component cyclocondensation with N-[3-oxo-3-(oxazol-4-yl)propanoyl]serine 251 and ammonia in methanol, in a 2,3,6-trisubstituted pyridine synthesis that proceeds with total regiocontrol. Bohlmann-Rahtz reaction of a chiral non-racemic enamine 312 and thiazolylpropynone 114 gives a terminal-protected pyridine-containing gamma-amino acid 311 in high optical purity in a sequential one pot multicomponent reaction that proceeds with total control of regiochemistry and with minimal racemisation. Further elaboration has established the first synthesis of the gamma-lactam acidic hydrolysate of the macrocyclic thiopeptide antibiotic cyclothiazomycin, a selective rennin inhibitor, in only four steps and 30% overall yield and has confirmed its structure.
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Gautier, Elisabeth C. L. "Synthetic approaches to epoxyquinol natural products." Thesis, University of East Anglia, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240835.
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Malhi, B. S. "Synthetic studies related to natural products." Thesis, University of Newcastle Upon Tyne, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381529.
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Payne, Lloyd James. "Synthetic studies towards selected natural products." Thesis, University of Sussex, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388677.
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Pothoulakis, Georgios. "Organised natural structures using synthetic biology." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/56916.
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Pattern formation is found widely throughout nature serving important roles in many different biological contexts. Multicellular organisms form patterns to enable new functions and pattern formation is also a crucial step for biological adaptation. The work presented here lays the foundations for the creation and control of multicellular growth patterns with a normally single-celled organism. The natural capacity for strains of Saccharomyces cerevisiae yeast to perform multicellular growth is here genetically and externally-controlled using synthetic biology tools. This allows S. cerevisiae grow in multicellular filamenting patterns, following a unique phenotype called pseudohyphal growth. Fine-control of the dynamic behaviour and gene expression of a colony of cells growing with this phenotype should enable fractal-like growth formations to be genetically-encoded. In this work, synthetic gene regulatory networks were first constructed in order to control genetic targets than induce or repress the pseudohyphal growth phenotype. This generated haploid and diploid yeast strains that can quickly switch to growing as filaments when simple chemical stimuli are externally provided or removed. In order to enable control over pattern formation with these strains, further genetic targets such as the BUD genes were investigated and the pseudohyphal growth phenotype was linked to previously described timer gene regulatory networks that dynamically change the expression of target genes over hours and days. These timer networks allowed cells to be programmed to transition from pseudohyphal growth back to normal yeast growth as the cells are grown in a colony over days. Finally, in an attempt to create controlled growth from pseudohyphal yeast so that fractal-like patterns could be made, new hybrid promoters with multiple modes of regulation were generated. These externally-inducible promoters were constructed to only express in mother cells after they have budded a daughter cell, and were designed in order to control how often filaments form new branches when S. cerevisiae grows in pseudohyphal form. While a full integration of the whole system to generate controllable fractal-like patterns was not achieved in the end, this study delivers several valuable new tools for yeast research and yeast synthetic biology.
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Ustriyana, Putu Ayu Ditta Sarita. "Natural and Synthetic Biomacromolecules in Biomineralization." University of Akron / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron1573830824042347.
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Hayes, John, Robyn L. Bellestri, and Lisa Goldstone. "Trends in Use and Effects of Synthetic Cannabinoids and Cathinones Pre- and Post-Amendment of the Controlled Substance Act in 2012." The University of Arizona, 2014. http://hdl.handle.net/10150/614187.
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Class of 2014 AbstractSpecific Aims: To compare trends in user demographics, clinical effects, and clinical outcomes associated with the use of synthetic cannabinoids and cathinones before and after signing into law the Synthetic Drug Abuse Prevention Act of 2012 on July 9, 2012. Methods: Reports generated by the National Poison and Drug Information Center’s Toxic Exposure Surveillance System were used to isolate calls regarding patients who reportedly used either synthetic cannabinoids or synthetic cathinones from July 2011 to March 2013. Clinical effects, clinical outcomes, and demographic information of patients associated with these calls from July 9, 2011 to July 8, 2012, were compared to that of patients associated with calls from July 9, 2012 to July 8, 2013. Main Results: Pending Conclusion: Pending
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Grim, Travis. "Synthetic cannabinoids versus delta-9-tetrahydrocannabinol: abuse-related consequences of enhanced efficacy at the cannabinoid 1 receptor." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4039.
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In the past ten years, synthetic cannabinoids (SC) have emerged as drugs of abuse. Unlike D9-tetrahydrocannabinol (THC), many SCs are associated with serious health complications and death. One way in which THC and SCs differ lies with their enhanced potency and efficacy at the CB1 receptor. No current methods exist to measure efficacy at the CB1 receptor in vivo, and the abuse-related properties of SC cannabinoids are not well explored. Here, we utilized CB1 wild type (WT), heterozygous (HET), and knockout (KO) mice. By employing CB1 ligands which differ in efficacy we have developed a method to explore the relationship between efficacy and the ability to produce cannabimimetic (catalepsy, hypothermia, and antinociception) effects when CB1 expression was reduced by half. Additionally, the intracranial self-stimulation procedure (ICSS) was utilized to investigate the effects of enhanced efficacy at CB1 upon reward processes using representative SC CP55,940. As predicted, the potency shift between WT and HET mice inversely correlated with the efficacy of the test drug for both hypothermia and antinociception, but not catalepsy. This efficacy stratification was correlated with the agonist-stimulated [35S]GTPgS binding assay, demonstrating this model as an effective tool to ascertain in vivo efficacy differences at CB1. In ICSS, CP55,940 elicited only rate-decreasing effects acutely, although tolerance developed following repeated dosing, with no evidence for spontaneous or rimonabant-precipitated withdrawal. Together, these data indicate that highly efficacious cannabinoid ligands require few receptors to produce cannabimimetic effects, and that the model provides an effective means to quickly ascertain differences in efficacy.
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Metternich, Sonja [Verfasser], and Carolin [Akademischer Betreuer] Huhn. "Advantages and limitations of spectroscopic, chromatographic and electrophoretic methods for the characterisation of synthetic cannabinoids and synthetic cathinone derivatives / Sonja Metternich ; Betreuer: Carolin Huhn." Tübingen : Universitätsbibliothek Tübingen, 2020. http://d-nb.info/1212849876/34.
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Davis, Nathan Ernest. "Experimental deformation of natural and synthetic dolomite." Thesis, Texas A&M University, 2005. http://hdl.handle.net/1969.1/2585.
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Natural and hot isostatically pressed dolomite aggregates were experimentally deformed at effective pressures of Pe = 50 ?? 400 MPa, temperatures of 400 ?? 850??C, and strain rates of ε& = 1.2x10-4 s-1 to 1.2x10-7 s-1. Coarse- and fine-grained dolomite deformed at low temperature (T ≤ 700??C for coarse-grained natural dolomite, T < 700??C for fine-grained natural and synthetic dolomite) exhibit mechanical behavior that is nearly plastic; differential stresses are insensitive to strain rate, fitted either by a power law no⎟⎟⎠⎞⎜⎜⎝⎛−=??σσεε31&& with n values that range from 12 to 49 or an exponential law ([31exp )] σσαεε−=o&& with exponential law term α values from 0.023 to 0.079 MPa-1. Microstructures of samples deformed at low temperatures include mechanical twins, and undulatory extinction suggesting that twin glide and dislocation slip are the predominant deformation mechanisms. At high temperatures (T ≥ 800??C) flow strengths of coarse- and fine-grained dolomite depend more strongly on strain-rate and exhibit pronounced temperature dependencies. Microstructures of coarse-grained dolomite samples deformed at T ≥ 800??C include undulatory extinction and fine recrystallized grains suggesting that recovery and dynamic recrystallization contribute to dislocation creep at these conditions. By comparison with lower temperature deformation, mechanical twinning is unimportant. Fine-grained synthetic dolomite deformed at high temperature (T ≥ 700??C) exhibits nearly linear (Newtonian) viscous behavior, with n = 1.28 (??0.15) consistent with grain boundary (Coble) diffusion creep. At low temperatures (T ≤ 700??C) coarse-grained dolomite exhibits higher strengths at higher temperatures which cannot be described by an Arrhenius relation, while fine-grained dolomite strengths show little or no temperature dependence. At high temperatures (T ≥ 800??C), dislocation creep of coarse-grained dolomite can be described by a thermally activated power law ⎟⎟⎠⎞⎜⎜⎝⎛−⎟⎟⎠⎞⎜⎜⎝⎛−=RTHno*31exp??σσεε&& with H*/n = 60 kJ/mol, or by an exponential law ()[]⎟⎟⎠⎞⎜⎜⎝⎛−−=RTHo*31expexpσσαεε&& with H*/α = 25447 kJ/mol. At high temperatures, diffusion creep of fine-grained synthetic dolomite can be described by ⎟⎟⎠⎞⎜⎜⎝⎛−⎟⎟⎠⎞⎜⎜⎝⎛−⎟⎠⎞⎜⎝⎛Ω=RTHdno*313exp??σσεε&& with H* = 280 ??45 kJ/mol. Taken together, the flow laws for coarse- and fine-grained dolomites constrain the high temperature conditions over which crystal plasticity, dislocation creep, and diffusion creep dominate.
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Jeon, Insik. "New synthetic methods for hypericum natural products." [Ames, Iowa : Iowa State University], 2006.
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Mandel, Alexander. "Synthetic studies applied to polyketide natural products." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3288813.
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Thesis (Ph. D.)--University of California, San Diego, 2008.Title from first page of PDF file (viewed January 14, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 142-155).
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Baker, Sara Jane. "Oxygen diffusion in natural and synthetic perovskites." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287878.
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Reeder, Andrew Tony. "Synthetic studies towards the pinguisane natural products." Thesis, University of York, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533477.
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Thom, Stephen M. "Synthetic studies with natural thiazoles and thiazolines." Thesis, University of Nottingham, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334420.
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Walker, Deborah Anne. "Synthetic approaches towards the natural product forskolin." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283449.
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Telling, Robert Henry. "The fracture of natural and synthetic diamond." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624385.
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Yoshimitsu, Yuji. "Synthetic Studies of Tetrahydrofuran-containing Natural Products." 京都大学 (Kyoto University), 2013. http://hdl.handle.net/2433/174546.
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Fletcher, Matthew James Edwin. "Synthetic studies towards (-)-Dysiherbaine." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268523.
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Montanari, Serena <1986>. "Cannabinoid system combined to classic targets for a new MTDL strategy: design and synthesis of natural inspired molecules for Alzheimer's disease." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6903/.
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In this thesis is described the design and synthesis of potential agents for the treatment of the multifactorial Alzheimer’s disease (AD). Our multi-target approach was to consider cannabinoid system involved in AD, together with classic targets.
In the first project, designed modifications were performed on lead molecule in order to increase potency and obtain balanced activities on fatty acid amide hydrolase and cholinesterases. A small library of compounds was synthesized and biological results showed increased inhibitory activity (nanomolar range) related to selected target.
The second project was focused on the benzofuran framework, a privileged structure being a common moiety found in many biologically active natural products and therapeutics. Hybrid molecules were designed and synthesized, focusing on the inhibition of cholinesterases, Aβ aggregation, FAAH and on the interaction with CB receptors. Preliminary results showed that several compounds are potent CB ligands, in particular the high affinity for CB2 receptors, could open new opportunities to modulate neuroinflammation.
The third and the fourth project were carried out at the IMS, Aberdeen, under the supervision of Prof. Matteo Zanda. The role of the cannabinoid system in the brain is still largely unexplored and the relationship between the CB1 receptors functional modification, density and distribution and the onset of a pathological state is not well understood. For this reasons, Rimonabant analogues suitable as radioligands were synthesized. The latter, through PET, could provide reliable measurements of density and distribution of CB1 receptors in the brain.
In the fifth project, in collaboration with CHyM of York, the goal was to develop arginine analogues that are target specific due to their exclusively location into NOS enzymes and could work as MRI contrasting agents. Synthesized analogues could be suitable substrate for the transfer of polarization by p-H2 molecules through SABRE technique transforming MRI a more sensitive and faster technique.
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Aldlgan, Abdulaziz. "Chromatographic analysis and survey studies to evaluate the emerging drugs of synthetic cannabinoids in Scotland and Saudi Arabia." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7579/.
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Synthetic cannabinoid receptor agonists or more commonly known as synthetic cannabinoids (SCs) were originally created to obtain the medicinal value of THC but they are an emerging social problem. SCs are mostly produced coated on herbal materials or in powder form and marketed under a variety of brand names, e.g. “Spice”, “K2”. Despite many SCs becoming controlled under drug legislation, many of them remain legal in some countries around the world. In Scotland, SCs are controlled under the Misuse of Drugs Act 1971 and Psychoactive Substances Act 2016 that only cover a few early SCs. In Saudi Arabia, even fewer are controlled. The picture of the SCs-problem in Scotland is vague due to insufficient prevalence data, particularly that using biological samples. Whilst there is evidence of increasing use of SCs throughout the world, in Saudi Arabia, there is currently no data regarding the use of products containing SCs among Saudi people. Several studies indicate that SCs may cause serious toxicity and impairment to health therefore it is important to understand the scale of use within society. A simple and sensitive method was developed for the simultaneous analysis of 10 parent SCs (JWH-018, JWH-073, JWH-250, JWH-200, AM-1248, UR-144, A-796260, AB-FUBINACA, 5F-AKB-48 and 5F-PB-22) in whole blood and 8 corresponding metabolites (JWH-018 4-OH pentyl, JWH-073 3-OH butyl, JWH-250 4-OH pentyl, AM-2201 4-OH pentyl, JWH-122 5-OH pentyl, JWH-210 5-OH pentyl, 5F-AKB-48 (N-4 OH pentyl), 5F-PB-22 3-carboxyindole)in urine using LLE and LC-MS/MS. The method was validated according to the standard practices for method validation in forensic toxicology (SWGTOX, May 2013). All analytes gave acceptable precision, linearity and recovery for analysing blood and urine samples. The method was applied to 1,496 biological samples, a mixture of whole blood and urine. Blood and/or urine samples were analysed from 114 patients presenting at Accident and Emergency in Glasgow Royal Infirmary, in spring 2014 and JuneDecember 2015. 5F-AKB-48, 5F-PB-22 and MDMB-CHMICA were detected in 9, 7 and 9 cases respectively. 904 urine samples from individuals admitted to/liberated from Scottish prisons over November 2013 were tested for the presence of SCs. 5F-AKB-48 (N-4 OH pentyl) was detected in 10 cases and 5F-PB-22 3-carboxyindole in 3 cases. Blood and urine samples from two post-mortem cases in Scotland with suspected ingestion of SCs were analysed. Both cases were confirmed positive for 5F-AKB-48. A total of 463 urine samples were collected from personnel who presented to the Security Forces Hospital in Ryiadh for workplace drug testing as a requirement for their job during July 2014. The results of the analysis found 2 samples to be positive for 5F-PB-22 3carboxyindole. A further study in Saudi Arabia using a questionnaire was carried out among 3 subpopulations: medical professionals, members of the public in and around smoking cafes and known drug users. With regards to general awareness of Spice products, 16%, 11% and 22% of those participants of medical professionals, members of the public in and around smoking cafes and known drug users, respectively, were aware of the existence of SCs or Spice products. The respondents had an overall average of 4.5% who had a friend who used these Spice products. It is clear from the results obtained in both blood and urine testing and surveys that SCs are being used in both Scotland and Saudi Arabia. The extent of their use is not clear and the data presented here is an initial look into their prevalence. Blood and urine findings suggest changing trends in SC use, moving away from JWH and AM SCs to the newer 5F-AKB-48, 5-F-PB-22 and MDMBCHMICA compounds worldwide. In both countries 5F-PB-22 was detected. These findings clarify how the SCs phenomenon is a worldwide problem and how the information of every country regarding what SCs are seized can help and is not specific for that country. The analytes included in the method were selected due to their apparent availability in both countries, however it is possible that some newer analytes have been used and these would not have been detected. For this reason it is important that methods for testing SCs are updated regularly and evolve with the ever-changing availability of these drugs worldwide. In addition, there is little published literature regarding the concentrations of these drugs found in blood and urine samples and this work goes some way towards understanding these.
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Pereira, Carlos Victor Montefusco. "Assessment of neuronal cytotoxicity of JWH-073 and JWH-250." Master's thesis, Instituto Superior de Ciências da Saúde Egas Moniz, 2014. http://hdl.handle.net/10400.26/6715.
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Dissertação de Erasmus Mundus para obtenção do grau de mestre em Técnicas Laboratoriais ForensesSynthetic cannabinoids from marijuana herbal blends like ‘Spice’ and ‘K2’ are drawing the attention of drug of abuse organizations, including the UNODC1, the EMCCDA2 and emergency hospital all over the world. This concern rises from clinical episodes of psychotropic effects that go beyond the regular range of marijuana and THC – namely, panic attacks, psychosis, catatonia, addiction and withdrawal symptoms. Our study addressed two emergent synthetic cannabinoids (napthtoylindoles) denominated JWH-073 and JWH-250 that are currently detected on ‘Spice’-like products, in order to observe their cell toxicity profile on neuronal cells in vitro model (SH-SY5Y). Using 0.2% DMSO as negative control, MTT and LDH results revealed that within concentrations of 1, 5, 10, 25, 37.5 and 50 μM, JWH-250 is identified as ‘toxic’ in a statistically significant manner at higher concentrations. This work did not detect any statistically significant toxicity from JWH-073. This data suggests to extend these studies on new synthetic cannabinoids to neuronal cells with increased concentrations, as well as the application of assays assessing apoptosis (conditions and signalling), neuronal function and activity (as cell membrane potential assay) within differentiated cells as neurons and glia. At the same time, the evaluation of herbal mixtures of more than one cannabinoids and plant types is advisable in order to understand synergic effects.
EACEA - European Commission
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Choi, Peter Jaein. "Synthetic studies towards aromatic polyketide derived natural products." Thesis, University of Auckland, 2011. http://hdl.handle.net/2292/6978.
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The first part of this thesis describes the successful synthesis of a series of 6,6- bisbenzannulated spiroketal analogues of the rubromycin family. The synthesis of spiroketals 183a-183e and spiroaminal 237 were successfully executed using a novel microwave-assisted DIHMA approach. Coupling of an aryl acetylene and an aryl aldehyde via acetylide anion addition resulted in the formation of an alkynol which was followed by oxidation to the desired ynone. Spirocyclisation using the DIHMA protocol afforded the desired bisbenzannulated spiroketals 183a-183e and spiroaminal 237 in good yields. Hydroxy-substituted 6,6- bisbenzannulated spiroketal 182 was successfully furnished by the reduction of ketosubstituted 6,6-bisbenzannulated spiroketal 183a with sodium borohydride. The second part of this research presents synthetic attempts to access the chiral 3-substituted phthalide containing natural products; aigialospirol (256) and herbaric acid (255). The synthesis of chiral vinylphthalide 406 proved challenging and was overcome by the use of a microwave-assisted chemoenzymatic resolution to install the C3 stereocenter of phthalide 406. Despite various attempts to functionalise vinylphthalide 406 towards the synthesis of aigialospirol, results were unsuccessful. With chiral vinylphthalide 406 in hand, the first synthesis and the structural assignment of (--)-herbaric acid (255) was accomplished. This was achieved via heteroatom-directed Wacker oxidation on vinylphthalide 406 to form aldehyde 460. Aldehyde 460 underwent smooth oxidation with Oxone® affording acid 488 which underwent facile methyl ester formation to facilitate purification, thus delivering enantioenriched lactone ester 489. Smooth demethylation with concomitant ester hydrolysis was effected by boron tribromide to give (--)-herbaric acid (255). The realisation of this entirely regioselective anti-Markovnikov addition of water during the Wacker oxidation provides a mild alternative to hydroboration/oxidation protocols that are traditionally used for terminal alkenes.Whole document restricted until August 2012, but available by request, use the feedback form to request access.
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Khan, Usman 1980. "Peroxidase-catalysed oxidation of natural and synthetic hormones." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98980.
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One of the fastest growing concerns in the wastewater treatment industry is the presence of estrogenic compounds in wastewater effluents that may threaten the reproductive success and development of aquatic organisms. The fact that such contaminants have been detected in surface waters at potentially detrimental levels indicates that conventional treatment plants are unable to effectively remove them; hence, supplementary treatment technologies must be considered. As one of these, enzymatic treatment offers numerous advantages which make such a treatment methodology almost tailor-made for the selective removal of such contaminants. In order to evaluate the potential for enzymatic treatment to be used to target important estrogenic compounds, the enzyme-catalysed oxidation of selected potent estrogens including estradiol, estriol and ethinylestradiol was studied. Horseradish peroxidase (HRP) enzyme was selected as the candidate enzyme since it is amongst the most studied oxidative enzymes and has been investigated extensively in waste treatment applications. Experiments were conducted at concentrations higher than those found in typical effluents in order to characterize the reactivity of the enzymes toward these compounds without being hampered by analytical difficulties. In order to gauge the importance/relevance of the data obtained for the enzymatic oxidation of estrogens parallel experiments were also conducted with phenol, which has been the subject of many past studies as a substrate of HRP and for which the technical feasibility of enzymatic treatment has been well established.HRP was able to effectively catalyse the oxidation of estrogens over a wide range of pHs, with optimal performance in the pH range typically experienced in wastewaters. Measurements of the stoichiometry of the reaction between estrogens and peroxide and also the enzyme dose required to achieve certain target levels of substrate removal suggested that the enzymatic oxidation of estrogens consistently had lower peroxide and enzyme requirements than phenol. In fact, phenol required between 2.5 and 5 times more enzyme than the estrogens to achieve various target levels of removal. For all substrates studied, similar kinetics of removal were found, provided that sufficient enzyme was added to reactions to compensate for differences in substrate affinity. In contrast to earlier studies conducted with HRP, minimal inactivation of the enzyme was observed during the treatment of all substrates. The lesser inactivation observed in the present study was probably due to the very low concentration of target substrates used. Collectively, the results indicate that the removal of estrogens is likely to be more feasible than phenol itself. It is also suggested that since the estrogen concentrations utilized here were an order of magnitude higher than environmentally-relevant concentrations and since the enzyme dose required and the level of inactivation observed are directly related to the amount of substrate targeted for treatment, the feasibility of removing estrogens may be more favourable at environmentally relevant values, except where kinetic limitations may dominate.
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Smith, Dustin Ryan. "Studies of natural and synthetic anti-inflammatory compounds." Oklahoma City : [s.n.], 2004.
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Sirichaisit, Jutarat. "Deformation processes in synthetic and natural polymer fibres." Thesis, University of Manchester, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488312.
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Turvill, Michael W. "The synthesis of natural and synthetic colouring materials." Thesis, University of Nottingham, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280103.
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Varnavas, Christalla Zenos. "Synthetic studies directed towards sesquiterpene-phenol natural products." Thesis, University of Salford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366319.
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Foot, Jonathan Stuart. "New synthetic methodology and antiviral natural product synthesis." Thesis, University of York, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412621.
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Andrew, R. G. "Synthetic studies on aaptamine and related natural products." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383699.
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Heltzel, Carl E. "Structural and synthetic studies of bioactive natural products." Diss., Virginia Tech, 1993. http://hdl.handle.net/10919/40067.
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Bioassay directed fractionation of the methyl ethyl ketone extract of Crescentia cujete resulted in the isolation of nine bioactive compounds, and detailed spectroscopic interpretation led to the assignment of their structures as (2S,3S)-3-hydroxy-5,6-dimethoxy dehydroiso-α-Iapachone [2.10], (2R)-5,6- dimethoxydehydroiso-α-Iapachone [2.11], (2R)-5-methoxy dehydroiso-alapachone [2.12], 5-hydroxy-2-(1'-hydroxyethyl)naphtho[2,3-b ]furan-4,9-dione [2.13], 2-(1 '-hydroxyethyl)naphtho[2,3-b ]furan-4,9-dione [2.14]' 2-isopropenylnaphtho[ 2,3-b ]furan-4,9-dione [2.15], 5-hydroxydehydro-iso-a-Iapachone [2.16], 3-hydroxymethylfuro[3,2-b ]naphtho[2,3-d]furan-5,10-dione [2.17], and 9- hydroxy-3-hydroxymethylfuro[3,2-b ]naphtho[2,3-d]furan-5,10-dione [2.18]. Compounds 2.10-2.12 are new, showing selective activity towards DNA repair-deficient yeast mutants. The selective DNA damaging activity of known compounds 2.13-2.16 is reported herein for the first time. Compounds 2.17 and 2.18 also show DNA damaging activity, and possess a novel fused ring system.
The bioactive sterols ergosta-5-24(28)-diene-3β,7α-diol [3.1] and 24,28- epoxyergost-5-ene-3β,7α-diol [3.2], originally isolated from Pseudobersama mossambicensis, have been synthesized from stigmasterol. In addition to these sterols, some of their analogs were prepared, and the bioactivity of all compounds were assessed.Ph. D.
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Tang, Shoubin. "Structural and Synthetic Studies of Bioactive Natural Products." Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/26104.
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As part of an ongoing investigation for anticancer agents from natural resources, four plant extracts were determined to contain interesting bioactivity. These extracts were separated by chromatography to afford a number of bioactive compounds that were characterized by spectral analysis.
Fractionation of the fruit extract of Cryptocarya crassifolia led to the isolation of two known flavonoids and two known cryptocaryalactones. Fractionation of the bark extract of the same plant also gave the same two cryptocaryalactones. All these compounds were weakly active in a cytotoxicity assay.
Two new isoflavones were isolated from the roots of an Egyptian lotus plant, Lotus polyphyllos. Both compounds were characterized by UV, NMR, and mass spectroscopic analysis
The methanol extract from the leaves and bark of a Brexiella sp. were found to display significant cytotoxic activity versus the A2780 mammalian cell line. Two highly active cardenolides, glucodigimetholide and xysmalogenin glucoside, were isolated and found to be responsible for the bioactivities. Both compounds were characterized by spectroscopic analysis and comparison to the known literature data.
Two marine extracts were also investigated. The pyridoacridine alkaloids, amphimedine and neoampimedine, were isolated from the marine sponge Petrosia sp., and three bromo-tyrosine alkaloids were isolated from the marine sponge Porphyria flintae. The structures of these known compounds were all elucidated by comparison to literature data.
Two 6-amino-glycoglycerolipids had been previously isolated from a marine algae species and shown to inhibit the activity of the enzyme Myt-1 kinase. These compounds and some related compounds were synthesized and their bioactivities against Myt1 kinase were determined.
Two isotopically labeled paclitaxel analogs (2D, 19F) were prepared in preparation for studies of the tubulin-binding conformation of paclitaxel by REDOR NMR. A new macrocyclic A-nor-paclitaxel was also synthesized, and was found to have good cytotoxicity and improved tubulin-binding activity as compared with paclitaxel.Ph. D.
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Shearman, James. "Bromotyrosine-derived natural products : synthetic and biological studies." Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/239411.
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Bromotyrosine-derived natural products are a fascinating class of compounds that areproduced by marine sponges of the order Verongida. Furthermore, they exhibit a richvariety of chemical structures and display a diverse range of bioactivities whichmakes them of great interest to both the chemical and biological researchcommunities. This thesis is divided into four Chapters and describes the total syntheses of fivebromotyrosine-derived natural products and analogues thereof. The anticancer activityof these compounds was also investigated. In addition, studies towards the totalsyntheses of the ceratamines are reported. The first Chapter gives a general introduction into the history, biosynthesis, structuresand biological activities of bromotyrosine-derived natural products. A backgroundinto the anticancer properties of ceratamines A and B is also provided. The research in Chapter two is concerned with bromotyrosine-derived oximes and isdivided into two parts. The syntheses of the natural products (5)-bromoverongamine,ianthelline and JBIR-44 are described in Part one and the structure-activityrelationship studies into these products is described in Part two. The total syntheses of subereamollines A and B are discussed in Chapter three. Furthermore, both enantiomers of the natural products were accessed and theirabsolute stereochemistry was unambiguously assigned. The first section of Chapter four provides an in-depth review of the research carriedout by the Andersen and Coleman groups into the ceratamines. This is followed by anaccount of the Ley group approach towards the syntheses of these natural products.
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Tworek, Luiza. "Development of a liquid chromatography - high resolution mass spectrometry method for multi-component screening of synthetic cannabinoids in blood." Thesis, Örebro universitet, Institutionen för hälsovetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-50803.
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Thomson, Peter. "Synthetic studies towards galbonolide B." Thesis, University of Sussex, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285131.
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Ravi, Janani. "CROSSTALK BETWEEN CANNABINOID RECEPTORS AND EPIDERMAL GROWTH FACTOR RECEPTOR IN NON-SMALL CELL LUNG CANCER." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1426697196.
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Foote, Kevin M. "Synthetic studies towards phomactin A." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243488.
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Townsend, Robert J. "Synthetic studies towards manzamine A." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266928.
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Thomas, Jason M. "Mechanistic studies of natural ribozymes and a synthetic DNAzyme." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/12563.
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This thesis reports the results of experiments designed to help elucidate the catalytic mechanisms of three RNA cleaving nucleic acid catalysts (the 9₂₅-11 DNAzyme, and the hammerhead and hairpin ribozymes). A number of enzymological and chemical probing experiments were employed in this regard, which were inspired by antecedent studies of RNA cleaving protein enzymes. First, a novel affinity labeling technique for nucleic acid catalysts was developed to probe general base catalysis. The affinity labeling substrate analogues bear a 2'-bromoacetamide modification at their cleavage sites. The second mechanistic probe employed was 5'-bridging phosphorothioate (S-link) substrate analogues, in which sulphur replaces the native oxygen leaving group. Investigation of S-link substrate cleavage in the context of active site mutations provided insight into general acid catalysis. A novel, simplified method for synthesizing S-link substrates is also presented. Several other experiments provided further mechanistic insight including pH-rate profiling, pKa perturbation, and the use of nonbridging phosphorothioate substrates.
Using many of the aforementioned experiments, the catalytic mechanism 9₂₅-11 DNAzyme (a synthetically modified DNAzyme that contains unnatural protein-like functional groups) was investigated in detail. The data suggest that 9₂₅-11 uses its synthetic functional groups to mimic the active site mechanism of the protein enzyme RNaseA.
Affinity labeling, pKa perturbation, and S-link cleavage experiments were also applied to the hammerhead ribozyme. The affinity labeling data suggest that the deprotonated N1 position of G12 acts as a general base catalyst. The results of pKa perturbation and S-link cleavage experiments provide strong evidence for a unique general acid mechanism in the hammerhead ribozyme. Therein, metal coordination is used to acidify a 2'-hydroxyl and thereby improve its ability to act as general acid.
Finally, affinity labeling was used to characterize the role of hairpin ribozyme G8 residue, which occupies a similar structural position to the hammerhead G12 residue. Affinity labeling indeed identified G8 as a potential general base in the hairpin ribozyme. The properties of the hairpin and hammerhead affinity labeling reactions are compared and the mechanistic implications are discussed.
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Friis, Henrik. "Luminescence spectroscopy of natural and synthetic REE-bearing minerals." Thesis, St Andrews, 2009. http://hdl.handle.net/10023/756.
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Lakshminarayan, Ganeshkumar. "Synthetic studies of diphenyl ether and anthraquinone natural products." [Ames, Iowa : Iowa State University], 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3403083.
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