Este trabalho tem como principais objetivos: desenvolver procedimentos sintéticos e novos materiais poliméricos que apresentem boa condutividade elétrica, estudar o comportamento eletro-óptico dos polímeros obtidos, desenvolver procedimentos para a construção de dispositivos eletroluminescentes, caracterizá-los e correlacionar as características eletro-ópticas observadas com a constituição da camada ativa polimérica. Foram realizadas diversas sínteses objetivando a preparação de polifluorenos com diferentes estruturas químicas a partir de monômeros difuncionais aromáticos boronados e bromados, utilizando uma mesma rota de acoplamento de Suzuki. Assim, foram preparados três polímeros, poli[2,7-(9,9-dioctilfluoreno)] (PF, polifluoreno), poli[1,4-fenileno-alt-2,7- (9,9-dioctilfluoreno)] [PFP, poli(fluoreno-fenileno)] e poli[(1,4-fenileno-2-flúor)-alt-2,7-(9,9- dioctilfluoreno)] [PFPF, poli(fluoreno-fenileno)fluorado]. Para obtenção destes polifluorenos com bom rendimento e com pureza adequada para a preparação de dispositivos poliméricos eletroluminescentes, foi necessário testar diversas condições de reação, até a otimização de um procedimento sintético robusto. Os polifluorenos preparados foram exaustivamente purificados por extração e solubilização-precipitação. Todos os polifluorenos tiveram a sua estrutura e composição químicas caracterizadas e confirmadas pelas técnicas de espectroscopia no infravermelho (FTIR), espectroscopia de ressonância magnética nuclear de hidrogênio (¹HNMR) e espectroscopia de energia dispersiva de raios-X (EDX). As massas molares médias e a polidispersão foram determinadas por cromatografia de permeação em gel (GPC). Soluções em clorofórmio dos polifluorenos foram analisadas por espectroscopias de absorção e emissão no UV-Vis. Estes resultados nos forneceram informações importantes quanto às propriedades de fotoluminescência dos polifluorenos obtidos. Até o momento, sabe-se que todos os três polímeros emitem cor azul e dentre as três estruturas estudadas, o PFPF apresentou maior intensidade de fluorescência. Para a fabricação dos P-OLEDs (Diodos Orgânico-Polimérico Emissor de Luz) foram feitas soluções de clorofórmio em concentrações de 1% dos três tipos de polímeros. Também foi estudada a influência dos compostos ETL (electron transport layer) (Alq3 ou butyl-PBD) com concentrações de 0,5%. Quando aplicada uma tensão no dispositivo, o PFPF apresentou menor tensão de operação entre os polímeros estudados. A partir das curvas de tensão vs. corrente, verificou-se que a adição do butyl-PBD nos três tipos de polímeros diminui a tensão de limiar em comparação com os dispositivos sem composto ETL. Os comprimentos de onda de eletroluminescência dos dispositivos polarizados permaneceram constante mesmo com a adição dos dois compostos ETL (Alq3 ou butyl-PBD). / This work has as main objectives: develop synthetic procedures and new electroluminescent polymeric materials that have good electrical conductivity, study the behavior of polymer systems thus obtained, and develop procedures for the construction of electroluminescent devices, characterize them and correlate the photo- electrical behavior with the features of the constitutive active polymeric layer Several syntheses were performed aiming at preparing polyfluorenes with different structures from boronated and brominated difunctional aromatic monomers using a Suzuki coupling route. So far, three polymers were prepared, poly[2,7-(9,9-dioctylfluorene)] (PF, polyfluorene), poly[1,4-phenylene-alt-2,7-(9,9-dioctylfluorene)] [PFP, poly(fluorenephenylene)] and poly[1,4-phenylene-2-fluoro)-alt-2,7-(9,9-dioctylfluorene)] [PFPF, fluorinated poly(fluorene-phenylene)]. To obtain these polyfluorenos with good yield and purity suitable for preparing polymeric electroluminescent devices, it was necessary to test various reaction conditions and to optimize a robust synthetic procedure. The polyfluorenes prepared were thoroughly purified by extraction and solubilization-precipitation. All polyfluorenes have had their structures and chemical composition characterized and confirmed by infrared spectroscopy (FTIR), and hydrogen and carbon-13 nuclear magnetic resonance spectroscopy (¹HNMR and 13CNMR). The average molar masses and polydispersity were determined by gel permeation chromatography (GPC). Polyfluorenes in chloroform solutions were analyzed by the UV-Vis absorption and emission spectroscopy. These results provided us with important information regarding the photoluminescence properties of polyfluorenes thus obtained. Until now, it is known that all three polymers emit in the blue region and among the three structures, the PFPF has the highest fluorescence intensity. The construction of PLEDs was carried out from the chloroform solutions at concentrations of 1% for each of the all three types of polymers. The influence of an ETL (electron transport layer) compound (Alq3, PBD) was also studied, and its concentration was kept constant at 5% in the polymer solution. Tests of the devices under applied voltage have shown a higher stability for PFPF among all. From the voltage vs. current curves, it was possible to observe that the addition of PBD decreased the threshold voltage for the devices prepared from the three types of polymers. The wavelength of electroluminescence remained constant despite the addition of the ETL compound (Alq3 or butyl-PBD).

Denna uppsats handlar om Suzukimetoden. Syftet med arbetet är att beskriva metoden med dess styrkor och svagheter samt att få förståelse för hur tidigare suzukielever ser på sin tid som suzukielev.   Den teoretiska bakgrunden utgörs av Lev Vygotskijs och Howard Gardners teorier. Utöver litteraturstudier har jag genomfört kvalitativa intervjuer med sex ungdomar/vuxna som tidigare varit suzukielever. De valde alla att sluta spela när de kom upp i tonåren. Det är deras berättelser som är studiens empiri.   Resultatet visar att personerna anser att suzukitiden betytt mycket positivt för dem. Framför allt lyfter de fram gemenskapen som de upplevde som suzukielever. Läger, kompisar och grupplektioner är roliga minnen som de bär med sig och som de anser har påverkat dem positivt. De positiva omdömena av undervisningen dominerar. I studien framkommer dock några områden som lärare och föräldrar behöver reflektera över. Det berör notinlärning, överdrivet föräldraengagemang och konkurrens. / This essay is about the Suzuki method. The purpose of this work is to describe the method and its strengths and weaknesses and to gain an understanding of how former Suzuki students view their studies in the Suzuki method.   The theoretical background consists of Lev Vygotsky and Howard Gardner’s theories. In addition to literature studies, I conducted interviews with six young adults who were Suzuki students and who chose to quit playing when becoming teenagers. It is their stories that are the study’s empirical evidence.   The results indicate that the Suzuki studies were very positive for them. Above all, they refer to the sense of community they felt as Suzuki students. Camp, friends and group lessons are fun memories that they share and which have been a positive influence. The positive reviews of teaching predominate. However, the study shows certain areas that teachers and parents need to reflect on. It affects note learning, excessive parental involvement and competition

Submitted by Samuel Campos de Pontes (samu.violino@gmail.com) on 2017-09-15T15:07:44Z No. of bitstreams: 1 Dissertação_Final_Samuel.pdf: 1111910 bytes, checksum: 97f2329fb78c73d2073d19bdb07c15ac (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-09-15T15:15:56Z (GMT) No. of bitstreams: 1 pontes_sc_me_ia.pdf: 1111910 bytes, checksum: 97f2329fb78c73d2073d19bdb07c15ac (MD5) / Made available in DSpace on 2017-09-15T15:15:56Z (GMT). No. of bitstreams: 1 pontes_sc_me_ia.pdf: 1111910 bytes, checksum: 97f2329fb78c73d2073d19bdb07c15ac (MD5) Previous issue date: 2017-06-12 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Partindo do trabalho realizado pela professora Shinobu Saito com o método Suzuki, esta pesquisa se propõe a refletir a respeito do ensino de música em nossa época, considerando os diversos aspectos desta metodologia e as implicações dessas ideias para o processo de ensino/aprendizagem. Para isso, considera-se a cultura japonesa e a visão de Suzuki acerca da Música e da Educação; o processo de Desenvolvimento Humano, na ótica de Vigotsky e algumas características do mundo contemporâneo. Esses aspectos aparecem no texto em contraponto com a História de Vida de Shinobu Saito, principal representante do método no Brasil. / Based on the work of the teacher Shinobu Saito with the Suzuki method, this research proposes to reflect on the teaching of music in our time considering the different aspects of this methodology and the implications of these ideas for the teaching/learning process. For this, one consider the japanese culture and Suzuki's vision of Music and Education; The process of Human Development, in Vygotsky's view and some characteristics of the contemporary world. These aspects rise in the text in counterpoint with the Life Story of Shinobu Saito, the main agent of the method in Brazil.

As cumarinas são compostos com potente atividade biológica. Foi explorada sua funcionalização, iniciando pela sua bromação, gerando o composto 3-bromocumarina, utilizado como material de partida para as reações de acoplamento do tipo Suzuki-Miyaura, que são uma das reações mais empregadas para a formação de ligação carbono-carbono, a qual utiliza paládio como catalisador e ácidos e ésteres borônicos como nucleófilo. Esses ácidos e ésteres borônicos possuem desvantagens, por isso foram substituídos pelos sais de organotrifluoroboratos de potássio, que são mais nucleofílicos, estáveis à umidade e à luz e não são higroscópicos. Assim, foi associada a catacterística reativa da cumarina para gerar derivados cumarínicos. Foram utilizados sais de ariltrifluoroboratos de potássio na primeira etapa e alquiniltrifluoroboratos de potássio na segunda etapa. Após o término destas duas etapas, foi utilizado o acoplamento de Sonogashira para a geração de um segundo material de partida, o 3-etiniltrimetilsililcumarínico, para poder sintetizar os 1,2,3-triazolilcumarínicos através da 1,3-dipolar cicloadição de Huisgen. Os 1,2,3-triazóis também possuem vasta atividade biológica, sendo de grande interesse sua preparação. / The coumarins are compounds with great biologic activity, for this reason in this dissertation we explored the functionalization beginning with bromination, generating the compound 3-bromocoumarin, used as starting material for the Suzuki-Miyaura cross-coupling reactions.The Suzuki-Miyaura cross-coupling reactions is one of the most employed protocol for carbon-carbon bond formation that use palladium as catalyst, boronic acid and ester as nucleophiles. But this boronic acid and ester have drawback and were substituted for potassium organotrifluoroborate salts that are more nucleophilic, moisture and light stable and are not hygroscopic. In this context, we associated the coumarin reactivity characteristic with the methodology mentioned above for create coumarin derivatives. We used potassium aryltrifluoroborate salts in the first step and potassium alkynyltrifluoroborate salts for the second step. After finished both steps mentioned before, we used the Sonogashira coupling to create the second starting material, the 3-((trimethylsilyl)ethynyl)-2H-chromen-2-one, so we could synthesize the 1,2,3-triazolyl coumarins through Huisgen 1,3-dipolar cycloaddtion. The 1,2,3-triazole also have a huge biologic activity, that represent a large interest for your preparation.

Orientador: Nelson Henrique Morgon / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-18T09:48:03Z (GMT). No. of bitstreams: 1 Silva_MauricioChagasda_D.pdf: 1640271 bytes, checksum: 4dc0aa6f7b350fe3e8808a9095aba5fe (MD5) Previous issue date: 2011 / Resumo: Utilizando a implementação do método da coordenada geradora discretizada nos orbitais atômicos, conjuntos de bases adaptados ao pseudopotencial de caroço SBKJC (conjuntos GBSMCS) foram desenvolvidos, validados e utilizados no estudo de possíveis efeitos de solvatação do tetraidrofurano sobre um mecanismo modelo de Suzuki-Miyaura. As metodologias de validação adotadas para os conjuntos GBSMCS foram os cálculos teóricos da afinidade por próton de sistemas atômicos e moleculares, iônicos e neutros, das entalpias de liquefação de alguns solventes orgânicos rotineiros e das entalpias de hidratação de 29 compostos orgânicos diversos. Nas etapas de validação, observou-se de uma maneira geral, uma boa relação entre custo e benefício na utilização dos conjuntos de bases GBSMCS, obteveram-se desvios médios por volta de 0 até 20 kJ.mol, nas propriedades estudadas. Com as metodologias propostas neste trabalho e com a utilização dos conjuntos GBSMCS, determinou-se o perfil potencial da reação modelo de Suzuki-Miyaura tanto em fase gasosa como em fase solvatada de tetraidrofurano. Não se observou efeitos significativos nas estruturas dos estados estacionários caracterizados e nem nas DrG para as etapas de adição-oxidativa, transmetalação, eliminação-redutiva e isomerização. Contudo, observou-se que há efeitos consideráveis de solvatação para as espécies individuais. As etapas de adição-oxidativa e de eliminação-redutiva apresentaram-se como sendo etapas exergônicas e a etapa de transmetalação como sendo uma etapa endergônica tanto em fase gasosa como em tetraidrofurano. Abordou-se um mecanismo associativo em todas as etapas principais reacionais, contudo inferiu-se que a etapa de transmetalação tenha possíveis rotas mecanísticas dissociativas iônicas que serão estudadas em trabalhos futuros / Abstract: Using the implementation of the discretized generator coordinate method in atomic orbitals, atomic basis sets adapted to the pseudopotential core SBKJC were developed ( GBSMCS ), validated and used to study possible effects of tetrahydrofuran¿s solvation over a model Suzuki-Miyaura¿s mechanism. The methodologies adopted for the validation of GBSMCS basis sets were the theoretical calculations of proton affinities of atomic and molecular, ionic and neutral, systems, the liquefaction enthalpies of some common organic solvents and the hydration enthalpies of 29 organic compounds. In the validation steps a good relationship was abserved between cost and benefit in the use of GBSMCS basis set, average deviations around 0 to 20 kJ.mol for the properties studied. Applying the methodologies proposed in this research and using the GBSMCS atomic basis sets, the potential profile of the Suzuki- Miyaura¿s model mechanism was determinated in the gas and tetrahydrofuran phases. No significant tetrahydronfuran¿s solvation effects were observed for molecular stationarys state structures, neither for DrG for oxidative- addition, transmetallation, reductive-elimination and isomerization reaction steps. However, some strong solvation effects were observed for individual species. The oxidative-addition and reductive-elimination reaction steps were characterized as exergonic steps, but transmetallation reaction step was presented as an endergonic step, both in the gas and tetrahydrofuran phases. This work approaches an associative mechanism for all main reaction steps; however, we inferred that the transmetallation reaction step could have some ionic pathways and should be studied in future works / Doutorado / Físico-Química / Doutor em Ciências

Este trabalho tem como principais objetivos: desenvolver procedimentos sintéticos e novos materiais poliméricos que apresentem boa condutividade elétrica, estudar o comportamento eletro-óptico dos polímeros obtidos, desenvolver procedimentos para a construção de dispositivos eletroluminescentes, caracterizá-los e correlacionar as características eletro-ópticas observadas com a constituição da camada ativa polimérica. Foram realizadas diversas sínteses objetivando a preparação de polifluorenos com diferentes estruturas químicas a partir de monômeros difuncionais aromáticos boronados e bromados, utilizando uma mesma rota de acoplamento de Suzuki. Assim, foram preparados três polímeros, poli[2,7-(9,9-dioctilfluoreno)] (PF, polifluoreno), poli[1,4-fenileno-alt-2,7- (9,9-dioctilfluoreno)] [PFP, poli(fluoreno-fenileno)] e poli[(1,4-fenileno-2-flúor)-alt-2,7-(9,9- dioctilfluoreno)] [PFPF, poli(fluoreno-fenileno)fluorado]. Para obtenção destes polifluorenos com bom rendimento e com pureza adequada para a preparação de dispositivos poliméricos eletroluminescentes, foi necessário testar diversas condições de reação, até a otimização de um procedimento sintético robusto. Os polifluorenos preparados foram exaustivamente purificados por extração e solubilização-precipitação. Todos os polifluorenos tiveram a sua estrutura e composição químicas caracterizadas e confirmadas pelas técnicas de espectroscopia no infravermelho (FTIR), espectroscopia de ressonância magnética nuclear de hidrogênio (¹HNMR) e espectroscopia de energia dispersiva de raios-X (EDX). As massas molares médias e a polidispersão foram determinadas por cromatografia de permeação em gel (GPC). Soluções em clorofórmio dos polifluorenos foram analisadas por espectroscopias de absorção e emissão no UV-Vis. Estes resultados nos forneceram informações importantes quanto às propriedades de fotoluminescência dos polifluorenos obtidos. Até o momento, sabe-se que todos os três polímeros emitem cor azul e dentre as três estruturas estudadas, o PFPF apresentou maior intensidade de fluorescência. Para a fabricação dos P-OLEDs (Diodos Orgânico-Polimérico Emissor de Luz) foram feitas soluções de clorofórmio em concentrações de 1% dos três tipos de polímeros. Também foi estudada a influência dos compostos ETL (electron transport layer) (Alq3 ou butyl-PBD) com concentrações de 0,5%. Quando aplicada uma tensão no dispositivo, o PFPF apresentou menor tensão de operação entre os polímeros estudados. A partir das curvas de tensão vs. corrente, verificou-se que a adição do butyl-PBD nos três tipos de polímeros diminui a tensão de limiar em comparação com os dispositivos sem composto ETL. Os comprimentos de onda de eletroluminescência dos dispositivos polarizados permaneceram constante mesmo com a adição dos dois compostos ETL (Alq3 ou butyl-PBD). / This work has as main objectives: develop synthetic procedures and new electroluminescent polymeric materials that have good electrical conductivity, study the behavior of polymer systems thus obtained, and develop procedures for the construction of electroluminescent devices, characterize them and correlate the photo- electrical behavior with the features of the constitutive active polymeric layer Several syntheses were performed aiming at preparing polyfluorenes with different structures from boronated and brominated difunctional aromatic monomers using a Suzuki coupling route. So far, three polymers were prepared, poly[2,7-(9,9-dioctylfluorene)] (PF, polyfluorene), poly[1,4-phenylene-alt-2,7-(9,9-dioctylfluorene)] [PFP, poly(fluorenephenylene)] and poly[1,4-phenylene-2-fluoro)-alt-2,7-(9,9-dioctylfluorene)] [PFPF, fluorinated poly(fluorene-phenylene)]. To obtain these polyfluorenos with good yield and purity suitable for preparing polymeric electroluminescent devices, it was necessary to test various reaction conditions and to optimize a robust synthetic procedure. The polyfluorenes prepared were thoroughly purified by extraction and solubilization-precipitation. All polyfluorenes have had their structures and chemical composition characterized and confirmed by infrared spectroscopy (FTIR), and hydrogen and carbon-13 nuclear magnetic resonance spectroscopy (¹HNMR and 13CNMR). The average molar masses and polydispersity were determined by gel permeation chromatography (GPC). Polyfluorenes in chloroform solutions were analyzed by the UV-Vis absorption and emission spectroscopy. These results provided us with important information regarding the photoluminescence properties of polyfluorenes thus obtained. Until now, it is known that all three polymers emit in the blue region and among the three structures, the PFPF has the highest fluorescence intensity. The construction of PLEDs was carried out from the chloroform solutions at concentrations of 1% for each of the all three types of polymers. The influence of an ETL (electron transport layer) compound (Alq3, PBD) was also studied, and its concentration was kept constant at 5% in the polymer solution. Tests of the devices under applied voltage have shown a higher stability for PFPF among all. From the voltage vs. current curves, it was possible to observe that the addition of PBD decreased the threshold voltage for the devices prepared from the three types of polymers. The wavelength of electroluminescence remained constant despite the addition of the ETL compound (Alq3 or butyl-PBD).

Face à l’apparition alarmante et continue de résistance massive des bactéries à l’arsenal actuel d’antibiotiques, la recherche de nouveaux agents antibactériens est actuellement un enjeu sociétal de tout premier ordre. Bien que connus depuis plus de 50 ans, les thiopeptides antibiotiques suscitent actuellement un très fort regain d’intérêt de la communauté scientifique internationale en raison de leurs propriétés antibactériennes remarquables, notamment contre les staphylococcus areus résistants à la méthiciline et les enterococci résistants à la vancomycine, impliquées dans de nombreuses infections qui engagent la vie des patients, et qui s’exercent de façon très intéressante selon deux modes d’action d’inhibition de la synthèse protéique originaux et encore inexploités en thérapie antibiotique humaine. Le travail développé s’inscrit dans ce programme international de valorisation pharmacologique qui repose pour une grande part sur le développement d’approches synthétiques rapides et modulables. Le projet a été centré en particulier sur la conception et la mise en oeuvre de nouveaux plans de synthèse des unités centrales di- ou trithiazolylpyridines, appelées coeurs hétérocycliques, communs à de nombreux thiopeptides de la série d et qui représentent les principaux défis synthétiques. Dans le cadre d’un programme de recherche du laboratoire ciblé sur l’étude de nouvelles méthodes de fonctionnalisation directe d’aromatiques et d’hétérocyclique, un premier travail méthodologique d’étude de la fonctionnalisation directe dans deux séries structurellement représentatives, thiazole-4-carboxylate et 2-cétothiazole, a été réalisé. Ainsi, une nouvelle méthodologie originale d’hétéroarylation directe pallado-catalysée régioselective du thiazole-4-carboxylate de tert-butyle avec une large gamme d’halogéno(hétéro)aromatiques a été développée avec succès. Une seconde méthodologie originale d’hétéroarylation directe de 4-bromo-2-cétothiazoles selon une séquence réactionnelle de boroylation pallado-catalysée suivie d’un couplage de Suzuki-Miyaura (BSC) a également été développée. Un second travail a porté sur l’exploitation des deux méthodologies de fonctionnalisation directe en série thiazolique développées et associées à la méthodologie de construction thiazolique de Hantzsch pour proposer et mettre en oeuvre un nouveau plan de synthèse expéditif et général d’accès aux coeurs hétérocycliques communs à une grande majorité des thiopeptides de la série d basé sur la fonctionnalisation séquencée d’un précurseur pyridinique aisément accessible. En particulier, la stratégie envisagée a permis, à partir des esters 5-bromopicolinates, la préparation tout d’abord d’un analogue thiazolique du coeur hétérocyclique des sulfomycines puis celle des coeurs hétérocycliques des micrococcines et des amithiamicynes. / Facing the alarmist and constant emergence of novel resistances of bacteria to the current arsenal of antibiotics, the research of novel antibacterial agents is of main importance in our modern society. Though being well-known since 50 years, the thiopeptide family display a high renewed of interest due to their high antibacterial properties against the Gram-positive bacteria, including the multi-drugs resistant staphylococcus areus strains (MRSA) and vancomycinresistant enterococci (VRE), through interestingly two original modes of action of the inhibition of the protein synthesis, yet unexploited by human therapeutics. The present work takes part of the current active international research program of pharmalogical valorisation of thiopeptides as novel human antibacterial therapeutics and one of the major points is the development of innovative and versatile synthetic approaches. Toward this direction, the project is mainly based upon the design of original synthetic strategy to the most synthetically challenging di- or trithiazolypyridines heterocyle cores of thiopeptide of serie d. In the course of a current research program on the development of metallo-catalyzed direct C-H(X) functionnalization in heteroaromatics series, the first part of this work had been focused on the setting of two innovative direct C-H(X) functionnalization methodologies in two structurally representative scaffolds, thiazole-4-carboxylate and 2- ketothiazoles. Thus, the direct regioselective C-H heteroarylation of thiazole-4-carboxylate as well as the direct C-Br heteroarylation of 4-bromo-2-ketothiazole through a boroylation Suzuki coupling sequence (BSC) have been examined. The last part of the work has been focused on the use of both novel direct C-H(Br) functionalization methodologies in thiazole series combined with the Hantzsch thiazole synthesis to propose a novel general and versatile synthetic approach toward the common heterocyclic cores of several thiopeptides of serie d through a pyridine modulation strategy from a ready available pyridine precursor. In particular, the novel developed strategy has been sucessfully applied to the preparation of the sulfomycinamate thio-analog as well as the heterocyclic cores of micrococcins and amithiamycins.

La recherche de nouvelles molécules à visée thérapeutique est un enjeu majeur pour la communauté scientifique et actuellement, 60% des médicaments utilisés cliniquement sont des produits naturels ou leurs analogues. Dans ce contexte, afin d’être capable de générer rapidement une bibliothèque de composés, le développement d’outils de synthèse efficaces est fondamental et c’est dans cette optique que s’inscrit le travail mené au cours de cette thèse. Les produits d’origine marine sont une source d’inspiration considérable dans le domaine de la création de nouveaux médicaments. Lors de ce travail, une attention particulière a été accordée à la ningaline B et à ses analogues avec pour objectif de mettre au point une voie d’accès simple et efficace. En effet, si la capacité de la forme hexaméthyléther à reverser la résistance aux anticancéreux par inhibition de la glycoprotéine-P a déjà été rapportée dans la littérature, l’étude d’analogues n’a été que peu exploitée.Dans ce contexte, une voie de synthèse reposant sur une étape clé de double couplage de Suzuki-Miyaura sur un dérivé (pseudo)dihalogéné symétrique a été proposée. Cette étape a fait l’objet d’une étude approfondie en envisageant deux approches. La première approche, basée sur des travaux antérieurs réalisés au laboratoire, a été de type simultané. Ainsi, à la manière d’une réaction multicomposante, tous les réactifs sont introduits dès le départ dans le milieu réactionnel. Cette méthode a montré des résultats intéressants dans le cas où deux dérivés borés électroniquement différents sont employés. En revanche, il a été montré que l’utilisation d’espèces borés électroniquement similaires était peu viable avec l’obtention d’un mélange statistique en produits de dicouplage. Toutefois, la préparation des cibles visées requérant l’utilisation d’aryles borés riches en électrons, une autre approche, séquentielle, a été envisagée. Après un travail d’optimisation sur des substrats simplifiés, avec pour objectif de disposer de conditions efficaces, adaptables, faciles avec des réactifs standards, une méthode de monoarylation de dérivés (pseudo)dihalogénés symétriques a été mise en place. Le champ d’application a ensuite été élargi en incluant les noyaux pyrroles nécessaires à la synthèse de la ningaline B et de ses dérivés. Ces travaux ont permis d’accéder aux molécules ciblées. En effet, une fois, les teraryles préparés, quelques étapes de manipulations fonctionnelles permettront d’avoir rapidement accès à de nombreux analogues. D’autre part, les motifs pouvant être obtenus par ce type de séquence réactionnelle pourraient être facilement dérivatisables afin de générer une bibliothèque d’analogues. / New therapeutic targets inversigation is one of the most serious challenges for the scientific community. Nowadays, 60% of clinically used drugs are natural products or their analogs. Thus, the development of new efficient synthetic tools to easily access such library of compounds is crucial. Marin natural products are an important source of inspiration for original drug design. Here we focused on development of an easy and efficient synthesis of ningalin B and its analogs. Indeed, while the literature reports the potential of the hexamethyl ether form to reverse multidrug resistance inhibing P-glycoprotein, only few studies have been done on analogs.Thereby, here we suggest a synthesis based on double Suzuki-Miyaura couplings on symmetrical dihaloarenes as a key step. This is a step to deal with studies in depth and two approaches have been envisaged. The first one relies on a previous simultaneous work in the laboratory. Thus, like a multicomponent reaction, all the starting materials are introduced in the mixture at the beginning of the reaction. This method show promising results when opposed electronic aryl boron derivatives are employ. Nevertheless, using electronic similar boron derivatives, a statistical mixture of dicoupling products is obtained. Since the preparation of our targets only needs the introduction of electron rich aryl moieties, a sequential approach has been envisaged. Preliminary optimizations afford optimal monocoupling conditions on symmetrical dihaloarenes. The scope of the reaction has then been studied including pyrrol nucleuses that are required for the synthesis of ningalins.This work led to desired molecules and analogs can be easily access in a few steps to fulfil a library of compounds.

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Die Immobilisierung homogener Katalysatoren ist eine wichtige Methode zur Realisierung der Abtrennbarkeit und Wiederverwendbarkeit aktiver Spezies. Im Rahmen dieser Arbeit wurde durch die Komplexierung von Palladium mit 1,4-Bis-(4′-pyrazolyl)benzen ein neues mikroporöses Koordinationspolymer generiert und dieses als heterogener Katalysator in der Suzuki-Miyaura-Kreuzkupplungsreaktion erfolgreich eingesetzt. Dabei konnten vollständige Umsätze und hohe Selektivitäten erzielt werden, die vergleichbar zu bereits kommerziell erhältlichen homogenen Katalysatoren sind. Die Besonderheit des Katalysators ist, neben dessen außergewöhnlich hohen chemischen Stabilität, die Variation seiner Struktureigenschaften durch die Wahl der Synthesebedingungen und die damit verbundene Steuerung seiner katalytischen Aktivität.