Organoboron compounds are highly valued synthetic intermediates due to their diverse array of reactivity, which is often utilized in the synthesis of valuable organic molecules. For this reason, there is significant interest in the development of novel borylation protocols, especially those whose products are suitable for further synthetic transformations towards valuable classes of compounds. Research in organoboron synthesis has been geared heavily toward transition metal-catalyzed addition to double and triple bonds, though an increasing number of publications detail transition metal-free borylation techniques involving substrate-mediated activation of a diboron reagent. This dissertation describes the author's contributions to the development of both a transition metal-catalyzed diboration and a transition metal-free protoboration. A transition metal-free diboration of alkynamides is described in Chapter 1 which uses the unsymmetrical, differentially protected diboron reagent, pinBBdan. The method installs both boron moieties in a regio- and stereoselective fashion. The products have synthetic value because they are shown to have chemoselectivity in downstream cross-coupling reactions; chemoselectivity is made possible by to the significant difference in Lewis acidity of the pinacol and diaminonapthalene-protected boron centers. This method allows for facile synthesis of tetrasubstituted alkenes with a set geometry about the double bond. A protoboration of allenes employing a Cu(II) catalyst under aqueous and atmospheric conditions is described. Though Cu(I)-catalyzed allene protoboration is well-described in the literature, this is the first report of an analogous Cu(II)-mediated process. The selectivity of the reaction is ligand-controlled, and moderate to good regioselectivities and yields can be achieved through use of a triphenylphosphine as ligand. The method is an environmentally friendly and facile means by which to borylate a challenging cumulated substrate. / Ph. D. / Organoboron compounds are valuable because of their ability to undergo a wide variety of chemical transformations, and they are often used as intermediates in the synthesis of challenging target molecules. In order for this reactivity to be exploited, methods must exist for the efficient synthesis of the desired boron-containing compound. This dissertation describes the author’s contributions to the development of two new methods by which to synthesize organoboron products. The first method involves installation of two differently ligated boron moieties onto an alkynamide substrate to produce a single, uncommon trans isomer as product. A synthetic application of these diboration products is described. The second method involves installation of a single boron moiety into allenes. Though the same overall transformation has been achieved in the literature with use of highly air-sensitive catalysts and organic solvents, the described method entails use of air-stable CuSO4 as catalyst and water as solvent. Therefore, the method is operationally simple and environmentally friendly relative to previously described methods.

O objetivo deste estudo foi avaliar in vitro a desadaptação cervical vertical de coroas confeccionadas com o sistema CEREC 3 utilizando dosi diferentes materiais para confecção de troquéis. Um modelo padrão em níquel-cromo foi confeccionado nas dimensões convencionais para o preparo de um canino superior. A partir da moldagem com silicone de adição do modelo mestre foram obtidos cinco troquéis com gesso Herostone (grupo 1) e conco com gesso CAM-base (grupo 2). Aos troquéis de gesso Herostone foi aplicado uma substância de contraste (CEREC powder). Os troquéis foram escaneados utilizando o sistema CEREC 3, por profissional calibrado, observando as orientações do fabricante. Dez coroas cerâmicas foram fresadas a partir das imagens obtidas no escaneamento. Com a utilização de um disco diamantado, foram marcados quatro pontos para medição da desadaptação marginal vertical no modelo padrão: vestibular, lingual, mesial e distal. As coroas forma fixadas no modelo padrão com adesivo à base de cianocrilato e posteriormente o conjunto modelo-padrão/coroa foram levados à observação no microscópio eletrônico de varredura sendo realizada quatro leituras em cada ponto, para obter a média, que foi considerado o valor da mensuração. Os resultados foram submetidos ao tratamento estatístico, aplicando-se os testes ANOVAOne Way e Tukey. Concluiu-se que as coroas confeccionadas com gesso CAM-base apresentaram menor desadaptação marginal vertical (69 um) em relação às produzidas com gesso Herestone mais aplicação CERC power (88 um). / The purpose of this study was to evaluate in vitro the inability to adapt marginal crown biult with the CERC 3 system use two unlike materials to making the die. A nickel-chromium pattern was made in conventional prportion an upper canine. A pattern model was impressing by adicion silicone and was made 5 dies with gypsum Herostone (group 1) and 5 dies with CAM-base gypsum (group 2). The dies were applied a contrast substance power CEREC. Those dies were scannied using a CEREC 3 system by qualified person, paying attention to the users guide. Ten ceramics crowns were passed a milling attending the images copied. Sing a diamond disk, were set four points to measure the marginal adapt into the pattern; bucal, lingual, mesial and distal. Those crowns were fixed into pattern with sticking made by cianocrilate and lately the pattern/crown were took get observation at the scanning electron microcopy, in prder to do the measures, were made four lectures in each point. The results were submitted to the statistics treatment, wich was applied the Anova one-way and Tuckey testis. Was achieved that the crowns made by gypsium CAM-base seemed less marginal desadaptation than respecting the does produced by gypsum Herostone plus the powder CEREC.

O presente trabalho está relacionado com o desenvolvimento e análise do desempenho eletroquímico de eletrodos compósitos do tipo nonwoven também chamados de free-standing binder/metal-free electrodes, em eletrólito líquido orgânico que contem íons de lítio. Os eletrodos de excelente resistência mecânica, livre de metais e binder, e que podem conter vários miligramas dematerial eletroativo por cm3, são constituídos por substratos de fibras de carbono derivado de poliacrilonitrila, e a carga eletroativa composta por nanotubos de carbono de parede múltipla (NTC) e nanotubos de MnO2 (NT). Foram utilizados dois tipos de substrato (denominados aqui de feltro e tecido de carbono) de diferentes condutividades eletrônicas e geometrias tridimensionais. O recobrimento das fibras de carbono dos nonwovens com NTC foi realizado por decomposição química de vapor (CVD) mantendo-se constante as variáveis operacionais, o que resultou em NTC do mesmo tipo para todas as amostras e um bom controle da massa depositada. O MnO2 foi incorporado por eletrodeposição em eletrólito aquoso, esse método garantiu um bom controle de massa eletrodepositada de NT. Os eletrodos obtidos foram caracterizados estruturalmente empregando-se microscopia de varredura (MEV), difração de raios-X e microscopia Raman. Para análise de desempenho eletroquímico e mecanismo de armazenagem/conversão de energia nos eletrodos empregadas as técnicas de voltametria e cronopotenciometria cíclicas. Os resultados mostram que os eletrodos compósitos são híbridos, podem atuar como capacitores e eletrodos de baterias de íons lítio. As metodologias aplicadas se mostram extremamente reprodutíveis reprodutivas e controláveis. Depedendo das composições e combinações foi possível obter capacidades específicas associadas com armazenagem/estocagem de lítio em altas densidades de corrente (A/g) na janela de potencial de 0,005 - 3,5V vs Li/Li+ (por exemplo, 800 mAh/g em 1 A/g, taxa C-rate = 1,25C, 400 mAh/g em 2,66A/g, taxa C-rate = 5C). A eficiência faradaica para o primeiro ciclo carga/descarga variou entre 83% e 54%, dependendo da quantidade de MnO2 e da corrente aplicada. Foi observado que é possível melhorar ainda mais os resultados com adição de outros constituintes, como por exemplo, a adição de partículas de prata (<1 % em peso). Neste caso os eletrodos forneceram eficiência faradaica de 83%, 1.100 mAh/g em 1,7A/g, em taxa C-rate = 1,66C e 550 mAh/g em 2,8A/g em taxa C-rate = 5C). Em termos de capacitância os compósitos também se mostram muito positivos. Valores de capacitância da ordem de 180F/g foram facilmente obtidos em tempos de descarga de 58s e num intervalo de potencial em relação ao Li/Li+ (~3,05 V vs H2/H+) de 1,4 a 3,8V vs Li/Li+, o que permite gerar densidade de energia e potência da ordem de 63 Wh/kg e 3,6 kW/kg respectivamente. Os eletrodos estudados podem atuar como eletrodo em baterias de íons lítio e em dispositivos de capacitores, o que significa que pode ser útil para o desenvolvimento de sistemas híbridos de armazenamento/conversão de energia, particularmente, de sistemas híbridos bipolar bateria-supercapacitor. / The present work is correlated with the development and electrochemical analisys of a nonwoven kind of electrode, also called as free-standing binder/metal-free electrodes, into lithium-ion liquid organic electrolyte, whereas the constituents are the substrate made of carbon fiber derived from carbonization of polyacrylonitrile, and the electroactive material which are defective multi-walled carbon nanotubes (MWCNT) and MnO2 nanotubes. Two types of nonwoven substrates (here denominated felt and cloth) with different electronic conductivity and three-dimensional geometry were employed. MWCNT coating of the nonwoven carbon fibers was achieved with chemical vapor decomposition (CVD) of methanol at same growth conditions, which resulted in electrodes with same type of MWCNT and a good control of the deposited mass. MnO2 was incorporaded by electrodeposition in aqueous electrolyte and this methodology was found appropriate to provide electrodes with same MnO2 NT loading, although the structural phase of MnO2 was affect by nonwoven substrate type. The robusts electrodes able to support several miligrams of electroactive material per cm3 obtained were structurally characterized using scanning electron microscopy (SEM, TEM), X-ray diffraction and Raman microscopy. It was employed cyclic voltammetry at different scan rate and chronopotentiometry (discharge/charge curves at galvanostatic conditions) aiming the understanding of the electrochemical performance and mechanism of energy storage/conversion of MnO2/MWCNT coated nonwoven electrodes. The results show that the composite electrode is hybrid, can act like capacitor or lithium ion battery electrode. It can provide very high specific capacity associated with storage/extraction of Li same in elevated gravimetric current density of A/g in the potential window of 0.005-3.5V vs Li/Li+ (e.g 800 mAh/g at 1 A/g, rate = 1,25C, 400 mAh/g at 2,66A/g, rate = 5C). The Faradic efficiency measure during the first charge/discharge cycle was between 83% to 54% depending on amount of MnO2 constituent and applied current. It was also observed a gain in the electrochemical performance of MnO2/MWCNT coated nonwoven electrode with Ag nanoparticles addition (about 1% wt). With presence of Ag constituent into the composites nonwovens it was found for instance 83% of Faradic efficiency at 1st discharge/charge cycle, 1,100 mAh/g at 1,7A/g rate = 1,66C and 550 mAh/g at 2,8A/g rate = 5C. In terms of capacitance the nonwoven were able to provide values like 180 F/g during 58s in high voltage window (1.4-3.8V vs LI/Li+) which correspond to energy and power density of 63 Wh/kg e 3.6 kW/kg, respectively. The electrodes developed in the present study could therefore act both as an electrode for Li intercalation and for capacitors devices, which means that it can be useful for the development of hybrid energy storage/conversion systems, particularly, bipolar battery-supercapacitor hybrid single.

O presente trabalho está relacionado com o desenvolvimento e análise do desempenho eletroquímico de eletrodos compósitos do tipo nonwoven também chamados de free-standing binder/metal-free electrodes, em eletrólito líquido orgânico que contem íons de lítio. Os eletrodos de excelente resistência mecânica, livre de metais e binder, e que podem conter vários miligramas dematerial eletroativo por cm3, são constituídos por substratos de fibras de carbono derivado de poliacrilonitrila, e a carga eletroativa composta por nanotubos de carbono de parede múltipla (NTC) e nanotubos de MnO2 (NT). Foram utilizados dois tipos de substrato (denominados aqui de feltro e tecido de carbono) de diferentes condutividades eletrônicas e geometrias tridimensionais. O recobrimento das fibras de carbono dos nonwovens com NTC foi realizado por decomposição química de vapor (CVD) mantendo-se constante as variáveis operacionais, o que resultou em NTC do mesmo tipo para todas as amostras e um bom controle da massa depositada. O MnO2 foi incorporado por eletrodeposição em eletrólito aquoso, esse método garantiu um bom controle de massa eletrodepositada de NT. Os eletrodos obtidos foram caracterizados estruturalmente empregando-se microscopia de varredura (MEV), difração de raios-X e microscopia Raman. Para análise de desempenho eletroquímico e mecanismo de armazenagem/conversão de energia nos eletrodos empregadas as técnicas de voltametria e cronopotenciometria cíclicas. Os resultados mostram que os eletrodos compósitos são híbridos, podem atuar como capacitores e eletrodos de baterias de íons lítio. As metodologias aplicadas se mostram extremamente reprodutíveis reprodutivas e controláveis. Depedendo das composições e combinações foi possível obter capacidades específicas associadas com armazenagem/estocagem de lítio em altas densidades de corrente (A/g) na janela de potencial de 0,005 - 3,5V vs Li/Li+ (por exemplo, 800 mAh/g em 1 A/g, taxa C-rate = 1,25C, 400 mAh/g em 2,66A/g, taxa C-rate = 5C). A eficiência faradaica para o primeiro ciclo carga/descarga variou entre 83% e 54%, dependendo da quantidade de MnO2 e da corrente aplicada. Foi observado que é possível melhorar ainda mais os resultados com adição de outros constituintes, como por exemplo, a adição de partículas de prata (<1 % em peso). Neste caso os eletrodos forneceram eficiência faradaica de 83%, 1.100 mAh/g em 1,7A/g, em taxa C-rate = 1,66C e 550 mAh/g em 2,8A/g em taxa C-rate = 5C). Em termos de capacitância os compósitos também se mostram muito positivos. Valores de capacitância da ordem de 180F/g foram facilmente obtidos em tempos de descarga de 58s e num intervalo de potencial em relação ao Li/Li+ (~3,05 V vs H2/H+) de 1,4 a 3,8V vs Li/Li+, o que permite gerar densidade de energia e potência da ordem de 63 Wh/kg e 3,6 kW/kg respectivamente. Os eletrodos estudados podem atuar como eletrodo em baterias de íons lítio e em dispositivos de capacitores, o que significa que pode ser útil para o desenvolvimento de sistemas híbridos de armazenamento/conversão de energia, particularmente, de sistemas híbridos bipolar bateria-supercapacitor. / The present work is correlated with the development and electrochemical analisys of a nonwoven kind of electrode, also called as free-standing binder/metal-free electrodes, into lithium-ion liquid organic electrolyte, whereas the constituents are the substrate made of carbon fiber derived from carbonization of polyacrylonitrile, and the electroactive material which are defective multi-walled carbon nanotubes (MWCNT) and MnO2 nanotubes. Two types of nonwoven substrates (here denominated felt and cloth) with different electronic conductivity and three-dimensional geometry were employed. MWCNT coating of the nonwoven carbon fibers was achieved with chemical vapor decomposition (CVD) of methanol at same growth conditions, which resulted in electrodes with same type of MWCNT and a good control of the deposited mass. MnO2 was incorporaded by electrodeposition in aqueous electrolyte and this methodology was found appropriate to provide electrodes with same MnO2 NT loading, although the structural phase of MnO2 was affect by nonwoven substrate type. The robusts electrodes able to support several miligrams of electroactive material per cm3 obtained were structurally characterized using scanning electron microscopy (SEM, TEM), X-ray diffraction and Raman microscopy. It was employed cyclic voltammetry at different scan rate and chronopotentiometry (discharge/charge curves at galvanostatic conditions) aiming the understanding of the electrochemical performance and mechanism of energy storage/conversion of MnO2/MWCNT coated nonwoven electrodes. The results show that the composite electrode is hybrid, can act like capacitor or lithium ion battery electrode. It can provide very high specific capacity associated with storage/extraction of Li same in elevated gravimetric current density of A/g in the potential window of 0.005-3.5V vs Li/Li+ (e.g 800 mAh/g at 1 A/g, rate = 1,25C, 400 mAh/g at 2,66A/g, rate = 5C). The Faradic efficiency measure during the first charge/discharge cycle was between 83% to 54% depending on amount of MnO2 constituent and applied current. It was also observed a gain in the electrochemical performance of MnO2/MWCNT coated nonwoven electrode with Ag nanoparticles addition (about 1% wt). With presence of Ag constituent into the composites nonwovens it was found for instance 83% of Faradic efficiency at 1st discharge/charge cycle, 1,100 mAh/g at 1,7A/g rate = 1,66C and 550 mAh/g at 2,8A/g rate = 5C. In terms of capacitance the nonwoven were able to provide values like 180 F/g during 58s in high voltage window (1.4-3.8V vs LI/Li+) which correspond to energy and power density of 63 Wh/kg e 3.6 kW/kg, respectively. The electrodes developed in the present study could therefore act both as an electrode for Li intercalation and for capacitors devices, which means that it can be useful for the development of hybrid energy storage/conversion systems, particularly, bipolar battery-supercapacitor hybrid single.

Thesis advisor: Amir H. Hoveyda / Catalytic enantioselective reactions are of great importance in synthetic organic chemistry. Thus, development of efficient, selective and easily accessible catalyst for various bond formations is the main task in our laboratories. First, we have developed the first broadly applicable enantioselective boryl conjugate addition reactions to a variety of α,β-unsaturated carbonyls, promoted by a chiral Lewis basic N-heterocyclic carbene. The valuable β-boryl carbonyls were further used in complex molecule syntheses. The mechanism of these C–B bond formations was studied in details. We have also developed a practical method for enantioselective addition of an allene unit to aryl-, heteroaryl- and alkyl-substituted Boc-aldimines. These efficient C–C bond formations, catalyzed by an aminophenol-derived boron-based catalyst, were further utilized in succinct syntheses of anisomycin and epi-cytoxazone. Finally, chiral NHC–Cu complexes were employed for site-, diastereo- and enantioselective silyl conjugate additions to acyclic and cyclic dienones and dienoates. The precious enantiomerically enriched allylsilane obtained can be converted into a ketone-aldol type product, which is difficult to access through alternative methods. / Thesis (PhD) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Piers-Rubinsztajn (P-R) conditions, involving catalysis by tris(pentafluorophenyl)borane, were applied to siliconize triarylamines. A phenylated linear methylhydrosiloxane copolymer was utilized to create a hydrolytically-stable composite with promising optical, electrochemical and thermal properties. However, the reaction was highly exothermic, had rapid uncontrollable kinetics and produced methane as a byproduct; problematic characteristics for larger scale syntheses. Thereafter, triarylamines with bulkier substituents were studied to determine whether the kinetics could be slowed and a less volatile byproduct created. The rate of conversion was retarded significantly as expected, but not all derivatives reacted quantitatively in ambient conditions. Finally, P-R conditions were applied to methylhydrosiloxane-dimethylsiloxane copolymers. Gelation in air upon extended reaction time was effectively avoided by “finishing” excess Si-H sites using anisole. The result was the preparation of composites with up to 61 wt % arylamine content, which are expected to have significant applications as cost-effective flexible hole transport layers in organic electronic devices.

Piers-Rubinsztajn (P-R) conditions, involving catalysis by tris(pentafluorophenyl)borane, were applied to siliconize triarylamines. A phenylated linear methylhydrosiloxane copolymer was utilized to create a hydrolytically-stable composite with promising optical, electrochemical and thermal properties. However, the reaction was highly exothermic, had rapid uncontrollable kinetics and produced methane as a byproduct; problematic characteristics for larger scale syntheses. Thereafter, triarylamines with bulkier substituents were studied to determine whether the kinetics could be slowed and a less volatile byproduct created. The rate of conversion was retarded significantly as expected, but not all derivatives reacted quantitatively in ambient conditions. Finally, P-R conditions were applied to methylhydrosiloxane-dimethylsiloxane copolymers. Gelation in air upon extended reaction time was effectively avoided by “finishing” excess Si-H sites using anisole. The result was the preparation of composites with up to 61 wt % arylamine content, which are expected to have significant applications as cost-effective flexible hole transport layers in organic electronic devices.

Submitted by Elielson Nobrega da Silva (nobrega_elielson@hotmail.com) on 2018-11-09T01:23:55Z No. of bitstreams: 1 Dissertação Ficha 08_11_1.pdf: 3453656 bytes, checksum: a1cff4951db4dde58ae977a59c6423b6 (MD5) / Approved for entry into archive by Silvana Alvarez null (silvana@ict.unesp.br) on 2018-11-19T18:56:22Z (GMT) No. of bitstreams: 1 silva_en_me_sjc.pdf: 3453656 bytes, checksum: a1cff4951db4dde58ae977a59c6423b6 (MD5) / Made available in DSpace on 2018-11-19T18:56:22Z (GMT). No. of bitstreams: 1 silva_en_me_sjc.pdf: 3453656 bytes, checksum: a1cff4951db4dde58ae977a59c6423b6 (MD5) Previous issue date: 2018-08-21 / A introdução da zircônia na Odontologia deu-se pela necessidade de melhores propriedades mecânicas dos materiais cerâmicos, pois com a crescente demanda estética, os cerâmicos tornaram-se materiais de largo uso, devido às suas propriedades estéticas e mecânicas. Em busca dessas propriedades, vários estudos analisaram a taxa de sobrevivência de restaurações zircônia-porcelana, relatando como uma das causas de falha a fratura precoce da porcelana de cobertura e o aumento significativo nos relatos clínicos de lascamento da porcelana de recobrimento aplicada sobre "coping" de zircônia. Diante desse problema, o objetivo deste trabalho foi determinar a tensão de falha no lascamento a partir de casos de clínicos e experimentais pertinentes a esse fenômeno em próteses fixas livres de metal .Foram coletados dados de artigos dos últimos 15 anos, por meio das bases de dados Pubmed e Google Schoolar, sendo selecionados para essa revisão os que obtiveram melhor abordagem do assunto, dando ênfase às possíveis causas de falhas nas restaurações cerâmicas dos casos clínicos e os ensaios realizados, visando um melhor entendimento desse fenômeno, via análise quantitativa e qualitativa, para melhor utilização e aproveitamento desse material na Odontologia. Para determinação da tensão de falha, foi empregada a mecânica da fratura linear elástica e determinado o fator de correção da trinca com base nas dimensões da trinca.Com a presente pesquisa, nota-se que amplitude de tensão influencia no processo de fratura, embora não tenha apontado exatamente para a causa da fratura. No entanto, pode-se inferir que uma baixa taxa de sobrevivência está relacionada a um grande defeito que, por sua vez, necessitou de uma sobrecarga para conduzir o processo de lascamento. Portanto, melhorias no processo de fabricação podem otimizar as características do material e sua aplicação final para suportar as tensões, a fim de aumentar a taxa de sobrevivência. / The introduction of zirconia in dentistry was due to the need for better mechanical properties of ceramic materials, because of an increasing aesthetic demand. Ceramics became widely used materials due to their aesthetic and mechanical properties. Aiming at these properties, several studies have analyzed the survival rate of zirconia-porcelain restorations, reporting as one of the causes of failure. Early porcelain fracture coverage and a significant increase in clinical reports of veneering porcelain applied over "coping "of zirconia. In view of this problem, the objective of this work was to determine the failure causes of chipping from clinical and experimental cases associated to this phenomenon in fixed metal free prostheses. Data from articles of the last 15 years were collected through the Pubmed and Google Schoolar databases. Those who obtained the best approach to the subject were selected for this analysis, emphasizing the possible causes of failures in the ceramic restorations of the clinical cases and the tests performed. Aiming for a better understanding of this phenomenon, via quantitative and qualitative analysis, to better use this material in dentistry. To determine the failure causes, linear elastic fracture mechanics were used and the crack correction factor was determined based on the crack dimensions. With the present research, it is noticed that stress amplitude influences in the fracture process, although it has not pointed exactly the cause of the fracture. However, it can be inferred that a low survival rate is related to a large defect, this in turn needed an overload to conduct the chipping process. Therefore, the manufacturing process can improve the characteristics of the material and its final application to withstand the stresses in order to increase the survival rate.

Les iminosucres sont des composés azotés polyhydroxylés mono- (pyrrolidine, piperidine, azepane) ou bicycliques (pyrrolizidine, indolizidine, nortropane) démontrant une forte activité inhibitrice envers les glycosidases, enzymes catalysant l'hydrolyse des liaisons glycosidiques des glycoconjugués. Le développement de nouveaux dérivés d'iminosucres est essentiel afin d'obtenir de nouveaux traitements contre des maladies comme le diabète de type II, la mucoviscidose ou les troubles du stockage lysosomale (maladies de Gaucher ou de Fabry par exemple). Des études récentes ont démontré que l'utilisation de systèmes multivalents d'iminosucres peut amener à des inhibitions plus fortes et plus sélectives envers les glycosidases comparés aux inhibiteurs monovalents. Cependant, une grande majorité de ces systèmes multivalents, incluant des systèmes multivalents basés sur une plateforme de type calixarène synthétisés au début de cette thèse, sont obtenus grâce à la cyclo-addition azoture alcyne catalysée par le cuivre(CuAAC). Malheureusement, cette réaction puissante mène à la contamination des systèmes multivalents par des quantités non négligeables d'ions cuivre toxiques. C'est pour cela que le principal but de ce doctorat a été de développer de nouvelles méthodes de ligations afin de former des architectures multivalentes d'iminosucres sans utiliser de catalyseurs métalliques toxiques.Premièrement, des ligations déjà exploitées pour la préparation de sucres multivalents comme l'addition radicalaire photoinduite d'un thiol sur un alcène terminal (couplage thiol-ène) et la ligation oxime ont été appliqués aux iminosucres avec succès. Ces approches ont alors permis de synthétiser des systèmes multivalents basés respectivement sur des plateformes de type calixarènes ou peptides cycliques.Dans un second temps, une nouvelle approche vers des systèmes multivalents de sucres et d'iminosucres a été développée en exploitant les remarquables stabilité et réactivité des fluorures de sulfonyle. Le couplage de ces derniers avec des partenaires portant une amine primaire a permis d'obtenir des clusters de sucres et d'iminosucres liés par une fonction sulfonamide avec de très bons rendements.Parallèlement, le couplage thiol-ène a permis la préparation simple et rapide de pseudo-disaccharides d'iminosucres, une nouvelle classe d'inhibiteur de glycosidases exhibant de meilleures activités et sélectivités que les iminosucres monosaccharidiques correspondants. Ce comportement est probablement du à la présence de l'unité saccharidique qui améliore l'analogie entre l'inhibiteur et les oligosaccharides naturels, substrats des glycosidases. / Iminosugars are naturally occurring, polyhydroxylated monocyclic (pyrrolidine, piperidine, azepane) and bicyclic (pyrrolizidine, indolizidine, nortropane) nitrogenated compounds endowed with strong inhibition activity against glycosidases, the enzymes that catalyse the cleavage of the glycosidic bonds in glycoconjugates. The development of new iminosugar derivatives is essential to obtain new treatments against diseases such as type II diabetes, cystic fibrosis or lysosomal storage disorders (Gaucher and Fabry diseases). Although the development of glycosidase inhibitors based on iminosugar clusters was not explored for a long period of time, recent studies have demonstrated that multivalent iminosugars are stronger and more selective inhibitors than the corresponding monovalent compounds. However, nearly two thirds of all the di- and multivalent iminosugars known to date, including the calixarene-based iminosugar clusters synthesized at the beginning of the thesis work, were obtained by means of the copper-mediated azide-alkyne cycloaddition (CuAAC). Unfortunately, this highly efficient reaction leads to the contamination of the multivalent compounds by significant amounts of noxious copper ions. Thus, the main aim of the present PhD research was the development of new ligation tools for the synthesis of multivalent iminosugars in the absence of metal catalysts. First, the ligations already exploited for the preparation of multivalent sugars, such as the photoinduced radical addition of thiol to terminal akenes (thiol-ene coupling) and the oxime ligation, were successfully applied to the iminosugars. Both approaches allowed the synthesis of iminosugar clusters based on calixarene and cyclopeptide scaffolds, respectively. Then, an unprecedented approach to multivalent sugars and iminosugars was developed taking advantage of the uncommon stability and reactivity of the sulfonyl fluoride moieties. The coupling of the latter with partners bearing a primary amine group afforded the corresponding sulfonamide-linked sugar and iminosugar clusters in high yield. Finally, the above-mentioned thiol-ene coupling also allowed the straightforward preparation of new iminosugar pseudo-disaccharides, a class of inhibitors endowed with higher glycosidase selectivity than the corresponding monosaccharidic iminosugar. This feature is due to the presence of the sugar unit which improves the analogy with the natural oligosaccharidic substrates of the glycosidases.

Carbon monoxide (CO) is an endogenous signaling molecule and has therapeutic values. However, the application of CO in the development of therapeutic options is hampered by the lack of pharmaceutically acceptable delivery methods. Inhalation of CO is not an ideal option for wide-spread clinical applications. Existing CO releasing molecules (CORMs) are mostly metal complexes, which have toxicity concerns to overcome. Some metal free CORMs have been developed. However, they all require light as a trigger to release CO, which limits their applications in vivo. Herein, we describe a metal-free CO prodrug approach using an intramolecular inverse electron-demanded Diels-Alder reaction. Such prodrugs can release CO spontaneously under physiological conditions with tunable release rates with the concomitant formation of a fluorescent reporter after CO releases. This intramolecular “click and release” strategy represents a milestone in the development of CO based therapeutics.