Depuis une quinzaine d’années, les polymères chiraux sont utilisés dans de nombreuses applications, comme phases stationnaires pour la séparation d’énantiomères ou encore en tant que catalyseurs en synthèse asymétrique. Aux vues de ces intérêts grandissants, de nombreuses méthodes ont émergé afin de les synthétiser. Nous nous sommes concentrés sur des méthodes organocatalytiques originales de synthèse de polymères chiraux par réaction de polyaldolisation et par désymétrisation de bis-anhydrides. Nous avons ainsi développé des processus de désymétrisation itératifs et ainsi généré une chiralité C-centrée sur la chaine polymérique. Des polyesters chiraux ont ainsi été obtenus avec de très bonnes séléctivités. / Chiral polymers are used in many applications such as stationary phases for chiral HPLC and catalysts in asymetric synthesis. The synthesis of chiral polymers traditionally deals with metal catalysts-based methodologies and often involved sensitive substrates. On the other hand, only a limited number of publications has been reported through environmentally-friendly organocatalytic pathways.The goal of this Ph.D. studies was devoted to the design of new routes toward chiral polymers under organocatalysis. We chose polyaldolisations and anhydride desymmetrizations with alcohols as key reactions to obtain original polymers with a C-centered chirality in the main polymer chain.

Les dérivés aminostéroïdiens analogues de la squalamine ont été largement étudiés pour leur large spectre d’activité sur les bactéries et les champignons multirésistants. Nous avons réalisé la synthèse de nouveaux dérivés aminostéroïdiens et présentant de nombreuses charges positives liées à la présence de groupements azotés, les 3,20-bis(polyaminostéroïdes) analogues de la squalamine. Une étude de la relation structure-activité a démontré l’importance des charges positives induites par la présence d’atomes d’azote dans les chaines carbonées portées par le motif cholestane. Nous avons mis en évidence les mécanismes d’action mis en oeuvre vis-à-vis des bactéries Gram positive et Gram négative. L’étude des activités antifongiques démontre que la squalamine et le dérivé aminostéroïdien DAS-1 possèdent de bonnes activités sur diverses souches de levures impliquées dans de nombreuses fongémies, avec des CMIs variant de 1 à 16 μg/mL. Nous avons étudié les applications potentielles de ces dérivés et démontré que ces dérivés en formulation de pommades à 1% de squalamine et de dérivé 3.20-bis(polyaminostéroïdien) étaient capables de réduire efficacement la colonisation cutanée à S. aureus sur un modèle animal. Il a été démontré que ces dérivés bis(polyaminostéroïdiens) sont également très actifs vis-à-vis de bactérie et de champignons multirésistants isolés des patients mucoviscidosiques. Nous avons testé leur activité en tant qu’agent désinfectant de matériel médical et plus particulièrement les nébuliseurs. La formation de cachets hydrosolubles à base de squalamine, nous a permis de développer un modèle de désinfection simple, rapide et peu onéreux des nébuliseurs contaminés. / Aminosterol derivatives analogues of squalamine possess a broad spectrum activity against multidrug resistant bacteria and fungi. We synthesized a new series of 3,20-bis(polyaminosteroïd) analogues involving a titanium reductive amination possessing numerous positives charges due to the presence of nitrogen groups. The study of relation structure-activity demonstrates that the nature of the amino group attached to the sterol plays a crucial role on antimicrobial activity of these compounds. We had also determined the mechanism of action of bis(polyaminosteroïd) on Gram negative and Gram positive bacteria. The study of antifungal activity of squalamine and aminosterol derivative ASD-1 show a good activity against various yeast responsible of fungal infections, minimal inhibitrice concentration ranging from 1 to 16 μg/mL. We studied a potential application of these compounds in human therapeutic. We evaluated squalamine and related parent-derived ointments (1%) as potential new compounds for S. aureus decolonization in a new mouse model. Using this model we found that squalamine ointment (1%) was able to reduce efficiently S. aureus colonization. Squalamine and bis(polyaminosteroïd) derivatives were actives against multidrug resistant bacteria and fungi isolated from cystic fibrosis patients. We investigated the potential use of squalamine compound in vitro in a nebulizer disinfection model. A formulation of squalamine disinfecting soluble tablets at 2.5 % (W/W) was developed and successfully applied for rapid nebulizer disinfection.

É notório o potencial farmacológico de lignanas, metabólitos secundários extraídos de produtos naturais, na sua maioria com baixos rendimentos. Usando a natureza como fonte de inspiração, foram propostas rotas sintéticas de compostos análogos, obtendo-se o 2,5-bis(2-metoxifenil)tiofeno, um análogo químico da lignana grandisina. De acordo com o potencial leishmanicida preliminarmente identificado, associado à reduzida citotoxicidade do análogo, despertou-se o interesse para o desenvolvimento de nova terapia medicamentosa para as leishmanioses em substituição aos tratamentos rotineiros e tóxicos utilizados. Entretanto, não há na literatura informações sobre os processos que abrangem a farmacocinética - absorção, distribuição, metabolismo e excreção (ADME) do composto. Portanto, o presente estudo objetivou a avaliação pré-clínica da disposição cinética do 2,5-bis(2-metoxifenil)tiofeno. Inicialmente foi desenvolvido um método analítico por cromatografia liquida de ultra eficiência acoplada a espectrometria de massas (CLUE-EM/EM) para quantificação do analito extraído da matriz de plasma, através de precipitação de proteínas com acetonitrila acidificada. O método foi validado de acordo com guias oficiais da Agência Nacional de Vigilância Sanitária e da Food and Drug Adminstration, mostrando-se sensível, exato, preciso e linear na faixa de 4 a 1000 ng.mL-1. A partir da administração intravenosa do 2,5-bis(2-metoxifenil)tiofeno em ratos foi possível obter curvas de decaimento plasmático versus tempo, observando-se que os dados adequaram-se ao modelo bicompartimental. O perfil farmacocinético do 2,5-bis(2-metoxifenil)tiofeno indicou rápida distribuição (t1/2? de 10,66 ± 2,37 min) e eliminação (t1/2? de 71,68 ± 13,84 min), não provocando acúmulo plasmático. / It is notorious the pharmacological potential of lignans, secondary metabolites extracted from natural products, mostly with low yields. Applying nature as a source of inspiration, synthetic routes of analogous compounds have been proposed getting 2,5-bis(2-methoxyphenyl)thiophene, a chemical analogue of lignan grandisine. According to the leishmanicide potential preliminarily identified, associated with the reduced cytotoxicity of the analogue, interest was aroused for the development of new drug therapy for leishmaniasis, replacing the typical and toxic treatments used. However, there is no information about the pharmacokinetics processes - absorption, distribution, metabolism and excretion (ADME) of the compound in the literature. Therefore, the present study aimed to evaluate the kinetic disposition of 2,5-bis (2-methoxyphenyl) thiophene. An analytical method was developed by ultra performance liquid chromatography coupled to mass spectrometry (UPLC-MS/MS) for quantification of the analyte extracted from the plasma matrix through precipitation of proteins with acidified acetonitrile. The method was validated in according to Agência Nacional de Vigilância Sanitária and Food and Drug Adminstration guidelines, showing to be sensitive, accurate, precise and linear over the concentration range of 4 to 1000 ng.mL-1. From the intravenous administration of 2,5-bis(2-methoxyphenyl)thiophene in rats it was possible to obtain the mean plasma concentration versus time profile, and the concentration data was best fitted to a two-compartment model. The pharmacokinetic profile of 2,5-bis (2-methoxyphenyl) thiophene indicated rapid distribution (t1 / 2? of 10.66 ± 2.37 min) and elimination (t1 / 2? of 71.68 ± 13.84 min), without plasma accumulation.

Les spirolides sont des phycotoxines marines macrocycliques neurotoxiques qui s’accumulent lors d’efflorescences algales, posant ainsi des problèmes de santé publique.Absorbés puis concentrés par les organismes filtreurs, ils sont ensuite potentiellement transmis,via la chaîne alimentaire, aux animaux marins et à l’Homme. A ce jour, le mode d’action des spirolides n’est pas totalement élucidé et la toxicité vis-à-vis de l’Homme reste encore à étudier. Dans ce but et compte tenu de leur faible biodisponibilité, leur synthèse s’avère indispensable pour disposer de quantités suffisantes à leur étude pharmacologique. Ces travaux de thèse, menés en collaboration avec l’équipe du Dr. Guillou à l’ICSN, visaient la synthèse totale du 13-desméthyle spirolide C, membre le plus toxique de la famille des spirolides (DL50 = 5-8 μg.kg-1i.p.). La stratégie de synthèse envisagée implique une déconnexion de la molécule en deux fragments. Notre cible, le fragment bis-spirocétal, a été obtenue par cyclisation en milieu acide d’une dicétone-1,4 issue d’une réaction de sila-Stetter. Ce manuscrit rapporte, dans un premier temps, l’étude de la réaction clé de type sila-Stetter, et, dans un second temps, les différentes approches ayant mené à la synthèse du fragment bis-spirocétal C10-C24 du 13-desméthyle spirolide C. Pour former les centres stéréogènes présents sur la dicétone-1,4 intermédiaire, des voies de synthèse énantiosélectives puis diastéréosélectives, reposant sur l’emploi de copules chirales, ont initialement été explorées. Finalement, ces centres ont été générés en exploitant le pool chiral et l’alcool tertiaire présent sur le fragment a été formé par régénération de chiralité. / Spirolides are marine macrocyclic neurotoxic phycotoxines which concentrateduring algal blooms, causing public health issues. First absorbed and concentrated by seafood,they are then potentially transmitted to marine wildlife and humans through the food chain. To date, the mode of action of spirolides is not fully elucidated and the toxicity toward humans stillneed studies. Considering their low bioavailability, their synthesis proves to be crucial to have enough material for pharmacological studies. These thesis works, performed in collaboration with Dr. Guillou’s team at ICSN, were aiming at the total synthesis of 13-desmethyl spirolide C, the most potent member of the spirolide family (IC50 = 5-8 μg.kg-1 i.p.). The envisioned synthetic strategy implies a disconnection of the molecule into two fragments. Our target, the bisspiroketal fragment, was obtained through acidic cyclisation of a 1,4-diketone formed via a sila-Stetter reaction. This manuscript first reports the methodology for the key sila-Stetter typereaction, and then the different approaches which have led to the synthesis of the C10-C24 bisspiroketalfragment of 13-desmethyl spirolide C. In order to form the stereogenic centers presents on the intermediate 1,4-diketone, enantioselective pathways and then diastereoselective pathways, relying on the use of chiral auxiliaries, were initially explored. Eventually these centers were generated from chiral pool and the tertiary alcohol present on the fragment was formed through self-regeneration of chirality.

Pirmoje darbo dalyje yra nagrinėjamos organizacijų ekonominės problemos ir ieškoma kaip tos problemos gali būti pašalintos. Išanalizavus kokios gali būti problemos pradėta analizuoti intelektualios verslo sistemos, kaip vienas geriausių sprendimo būdų. Darbe taip pat nagrinėjama intelektualių sistemų apibrėţimas, paaiškinama architektūra ir išskiriama kuo BIS skiriasi nuo kitų informacinių valdymo sistemų. Antroje dalyje yra nagrinėjamos pagrindinės problemos susijusios su intelektualiomis verslo sistemomis ir jų diegimu organizacijose. Analizuojama šiuo metu labiausiai paplitusios technologijos OLAP ir QlikView, kurios naudoja atmintį duomenų krovimui. Analizuojami jų privalumai ir trūkumai taip pat skirtumai. Trečioje dalyje analizuojama intelektualių verslo sistemų projektavimo metodika. Keliami klausimai ką reikia daryti, kad gautume sistemą atitinkančią organizacijos lūkesčius. Analizuojama projektavimo struktūra naudojant UML diagramas, taip pat elementų svarba pačioje sistemoje. Ketvirtoje dalyje yra projektuojami intelektualių verslo sistemų modeliai, kurie yra tik pavyzdiniai, kurie parodo kokie privalumai ir kaip veikia intelektualios verslo sistemos vykdant pirkimo funkcijas panaudojant marketinginius principus. / In the first part of master thesis analyzing the main problems, which are in organization management. The main purpose of this part is to find a solution how can resolve this problems. Business intelligence systems are the best solution. In this part analyzing business intelligence systems definition, architecture and also analyze what is different in business intelligence systems comparing with other informatics management systems. The second part of work analyzes business intelligence problems related with creation, developing and using BIS. Analyze the most popular tools like OALP and QlikView. Compare the OLAP and QlikView. Analyze QlikView like data loading from memory. Explain the advantages and disadvantages of QlikView and OLAP. The third part analyzes designing and planning of business intelligence systems. Analyze what is the main purpose to create good system which will be useful in organizations. In this part also analyze the UML modems for BIS. In the last part is presenting solutions for problems which was analyzed in the second part. The examples are created using UML diagrams.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study describes the attainment of twenty three (23) bis-heterocycles derived from the Levulinic Acid: Bis-Pyrazoles (6a-k) by the reaction of cyclecondensation between the 3-(5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-3-il)propanohidrazidamand a series of replaced β-alcoxiviniltrifluorometilcetonas. 1,3,4-oxadiazole 2-5-disubstituted (8-11) by reactions like [4 + 1] [OCNN+C], through the reactions of cyclecondensation between the 3-(5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-3-yl)propanohidrazida with different orthoesters as well as with carbon disulfide. It was also produced hydrazides (16c-d, g-h e 17c-d, g-h) derived of synthesized pyrimidines, to be used as precursorsn in the synthesis of bis-heterocycles, derivatizated of the reaction of those with some β- Ketones alcoxiviniltrifluormetil. The bis-heterocycles were obtained by the ordinary methodology, with efficiency between 61-97%.It was also gotten other original compounds (3i-k, 5), used as precursors in this study. The structure of these synthesized compounds were confirmed by the data of RMN 1H, 13C, besides the data of mass spectrometry. / Este trabalho descreve a obtenção de 23 novos bis-heterociclos derivados do Ácido Levulínico: Bis-Pirazóis (6a-k) a partir da reação de ciclocondensação entre o 3-(5-(trifluorometil)-4,5-dihidro-1H-pirazol-3-il)propanohidrazida e uma série de β-alcoxiviniltrifluorometilcetonas substituídas; 1,3,4-oxadiazóis 2-5-dissubstituídos (8-11) via reações do tipo [4 + 1] [OCNN+C], através de reações de ciclocondensação entre a 3-(5-(trifluorometil)-4,5-dihidro-1H-pirazol-3-il)propanohidrazida com diferentes ortoésteres, bem como com dissulfeto de carbono. Foram produzidas ainda, hidrazidas( 16c-d, g-h e 17c-d, g-h) derivadas de pirimidinas sintetizadas, para serem utilizadas como precursores na síntese de bis-heterociclos, derivatizados da reação destas com algumas β-alcoxiviniltrifluormetil cetonas. Os bis-heterociclos foram obtidos por metodologia convencional, com rendimentos entre 61-97%. Foram obtidos ainda outros compostos inéditos (3i-k, 5) utilizados como precursores nesse trabalho. As estruturas dos compostos sintetizados foram confirmadas por dados de RMN 1H, 13C, além de dados de espectrometria de massas.

Submitted by ANA KARLA PEREIRA RODRIGUES (anakarla_@hotmail.com) on 2017-08-02T13:41:04Z No. of bitstreams: 1 arquivototal.pdf: 3866821 bytes, checksum: 1b8fc11ea5100eea54ea37850025d528 (MD5) / Made available in DSpace on 2017-08-02T13:41:04Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 3866821 bytes, checksum: 1b8fc11ea5100eea54ea37850025d528 (MD5) Previous issue date: 2016-02-29 / This work reports the synthesis, characterization and the investigation of photoluminescence properties of systems [Ln(DPM)2(NO3)(L)2] and [Ln(L)3(NO3)3] (where L = THPO or TPPO and Ln3+ = Tb3+, Gd3+ or Eu3+), and the dimeric compounds [Eu2(DPM)6] and [Tb2(DPM)6]. The compounds were characterized by elemental analysis of CHN, vibrational spectroscopy in the infrared region, thermogravimetric analysis and their spectroscopic properties were investigated by molecular diffuse reflectance, excitation and emission as well as decay times of emitting states. The experimental data of CHN analysis and complexometric titrations of the synthesized complexes are in agreement with theoretical data for their respective formulas. The absorption spectra in the infrared region show that the coordination of β-diketonate and phosphine oxide ligands to the Ln3+ ions occurs by the oxygen atoms of carbonyl groups and P=O, respectively. The structural behavior of complexes [Eu(DPM)2(NO3)(TPPO)2] and [Tb (DPM)2(NO3)(TPPO)2] is significantly different from those dimeric ones [Eu2(DPM)6] and [Tb2(DPM)6]. In addition, the complex [Tb(DPM)2(NO3)(TPPO)2] presented fractoluminescence phenomenon, emitting green light when its crystals are broken. The presence of metal ligand charge transfer state (TCLM) of low energy in compounds of Eu3+ was also investigated. The luminescent properties studies showed that the bis-DPM systems Eu3+, an increase occurs in the energy state of TCLM, contributing to an increase in luminescence intensity of these compounds, when compared with dimeric complexes. This observation is evidenced by the luminescence at room temperature observed for the first compound, which is not observed for the second. The geometries of complexes [Ln2(DPM)6] and [Ln(DPM)2(NO3)(L)2] with Ln = Tb3+ or Eu3+ were optimized using SPARKLE/RM1 method, the first having a coordination polyhedron described by a monocapped trigonal prism trigonal and the second as distorted dodecahedron. / O presente trabalho envolve a síntese, caracterização e a investigação das propriedades fotoluminescentes dos complexos de fórmulas [Ln(DPM)2(NO3)(L)2] e [Ln(L)3(NO3)3], em que L = triciclohexilfosfinóxido (THPO) ou trifenilfosfinóxido (TPPO) e Ln3+ = Tb3+, Gd3+ ou Eu3+, além dos compostos diméricos [Eu2(DPM)6] e [Tb2(DPM)6]. Todos os sistemas foram caracterizados por análise elementar de CHN e Lantanídeo (Ln), espectroscopia vibracional na região do infravermelho, análise termogravimétrica e suas propriedades espectroscópicas foram investigadas por espectroscopia molecular de reflectância difusa, de excitação e emissão, assim como por medidas de tempos de decaimento dos estados emissores. Os dados experimentais das análises de CHN e titulações complexométricas dos complexos sintetizados estão em concordância com os dados teóricos calculados para as suas respectivas fórmulas. Os espectros de absorção na região do infravermelho evidenciam que a coordenação dos ligantes β-dicetonatos e fosfinóxidos aos íons Ln3+ ocorre por meio de átomos de oxigênio dos grupos carbonila e P=O, respectivamente. O comportamento estrutural dos complexos [Eu(DPM)2(NO3)(TPPO)2] e [Tb(DPM)2(NO3)(TPPO)2] é significativamente diferente daqueles complexos diméricos, [Eu2(DPM)6] e [Tb2(DPM)6]. Além disso, o complexo [Tb(DPM)2(NO3)(TPPO)2] apresentou o fenômeno de fractoluminescência, emitindo luz verde quando seus cristais são quebrados. A presença de estados de transferência de carga ligante-metal (TCLM) de baixa energia nos compostos de Eu3+ também foi investigada. Os estudos das propriedades luminescentes mostraram que nos sistemas bis-DPM de Eu3+, ocorre um aumento na energia do estado de TCLM, contribuindo para um aumento na intensidade de luminescência destes compostos, quando comparados com os complexos diméricos. Esta observação é evidenciada pela luminescência à temperatura ambiente observada para o primeiro composto, que não é observada para o segundo. As geometrias dos complexos [Ln2(DPM)6] e [Ln(DPM)2(NO3)(L)2] com Ln = Tb3+ ou Eu3+ foram otimizadas usando o método SPARKLE/RM1, o primeiro apresentando um poliedro de coordenação descrito como prisma trigonal monoencapuzado e o segundo como dodecaedro distorcido.

The purpose of this thesis is to analyse in detail the issue of consumer protection within the Brussels I bis regulation, establishment of the international court jurisdiction and the question of recognition and enforcement of a judgement. The thesis concentrates especially on a different position of consumer and measures that amend his situation. The thesis is composed of 9 chapters that are further divided into subchapters and points. Chapter One is an introductory chapter focusing on a consumer and defining reasons for his protection. Chapter Two explains the topic of international private law and european international private law, including the European judicial area. Chapter Three describes the development of legislation in the area of judicial cooperation in civil matters since the Brussels convention up to the Brussels I bis regulation and mentions respective changes. The chapter also focuses on different status of certain countries within the European judicial cooperation. Chapter Four examines the subject of regulation of Brussels I bis, lists the types of jurisdictions and looks at its specifics. It also investigates the applicability of regulation from the temporal, material, territorial and personal scopes of application. Chapter Five concerns several institutes. It defines the term...

La loi du 6 juin 2006 sur la gestion des déchets radioactifs de haute activité et à vie longue prévoit la recherche de solutions permettant la séparation et la transmutation des radioéléments à vie longue, pour réduire les quantités et la nocivité des déchets radioactifs ultimes. Ces déchets issus du retraitement du combustible nucléaire usé sont actuellement vitrifiés à La Hague. Ainsi, le projet " séparation poussée " vise à compléter le procédé industriel PUREX par le développement de procédés permettant d'extraire les actinides mineurs des raffinats PUREX où se trouvent également des produits de fission constitués principalement de lanthanides, neutrophages. Pour réaliser la séparation poussée, les actinides mineurs des raffinats PUREX doivent être séparés par des molécules spécifiques. Les BTP ou bis-triazinyl-pyridines ont été largement étudiées au CEA pour la séparation actinides(III)/lanthanides(III). Elles complexent sélectivement les actinides, mais l'origine de cette sélectivité n'est pas complètement expliquée : notamment l'influence des groupements (attachés à leur structure) sur la complexation ou la sélectivité reste à démontrer. En outre, elles sont sensibles à l'hydrolyse et à la radiolyse. La première partie du travail présente la synthèse de BTP ou de BTBP, différemment substituées pour améliorer leur résistance face à l'hydrolyse ou à la radiolyse, et une nouvelle famille de ligands polyaromatiques azotés : les BPBT, présentant un enchaînement original de cycles pyridine et triazine, différent de toutes les structures décrites jusqu'à présent dans la littérature. La seconde partie de ce travail est consacrée à l'étude physico-chimique de nouvelles molécules obtenues, en déterminant leurs constantes de protonation et de complexation, pour connaître l'influence des différents groupements sur la complexation et la sélectivité. Enfin, le troisième volet concerne l'étude des propriétés de ces ligands en extraction liquide-liquide, utilisés soit comme extractants lipophiles, soit comme complexants hydrophiles.