Cellulose is an extraordinarily abundant polymer that can be harvested and purified from trees and other renewable sources. Cellulose derivatives have been widely used as coatings, optical films, fibers, molded objects, and matrices for controlled release. The properties of cellulose derivatives are not only affected by the degree of substitution, but also by the position of substitution. In order to establish the structure-property relationships of cellulose derivatives, it is of great importance to impart regioselectivity into functionalized cellulose. However, regioselective substitution of cellulose is extremely challenging, especially in the synthesis of regioselectively functionalized cellulose esters due to the unstable ester bond under aqueous alkaline or acid conditions. In this dissertation, the main objective is to search for new tools to synthesize regioselectively substituted cellulose esters, to understand how structural changes impact properties and performance, and thus to design cellulose derivatives delivering high performance. Several strategies for regioselective preparation of cellulose esters are discussed in detail. The obtained regioselective cellulose esters were fully characterized analytically. / Ph. D.

This dissertation presents enabling technologies to fabricate thermo-responsive polymer composite based Lab-on-a-Chip (LOC) devices. LOC devices, also known as micro-total-analytical systems (microTAS) or microfluidic devices can amalgamate miniaturized laboratory functions on a single chip. This significant size reduction decreases the amount of required fluid volumes down to nano or pico-liters. The main commercial application of LOC devices is the biomedical fields. However, these devices are anticipated to make a technological revolution similar to the way miniaturization changed computers. In fact, medical and chemical analyses are predicted to shift from room-sized laboratories to hand-held portable devices. This dissertation is divided into three technologies. First, a series of terpolymer systems were synthesized and characterized to fabricate crosslinked coatings for phototunable swelling and create chemically patterned regions in order to conjugate cationic markers, proteins, or nanoparticles to the terpolymer coating. Second, antifouling surfaces were fabricated using magnetic thermo-responsive hydrogel structures via soft lithography. The structures were remote control activated with the use of AC magnetic fields. Finally, in order for LOC devices to fulfill its promise of bringing a laboratory to a hand-held device, they will have to be integrated with CMOS technology. Packaging will play a crucial role in this process. The last section will focus on the importance of coefficient of thermal expansion (CTE) mismatch in multi-chip modules. For the first technology, multi-functionalized terpolymer systems have been developed comprising of three units: N-isopropylacrylamide (NIPAAm), a stimuli responsive monomer that swells and collapses in response to temperature; methacryloxybenzophenone (MaBP), a photo-crosslinkable monomer that is activated at λ = 365 nm; and phenacyl methacrylate (PHEm), a photolabile protected functional group that generates localized free carboxyl groups in response to deprotection at λ = 254 nm. The multifunctional terpolymers can be spin-casted to form thin films of well-defined thickness, photo-crosslinked by a long UV wavelength light (λ = 365 nm) to form distinct structural patterns, and subsequently photo-chemically modified by a short UV wavelength light (λ = 254 nm). The photocleavage reaction by UV irradiation allows the production of free carboxylic groups that can be used to conjugate cationic markers, proteins, or nanoparticles to the terpolymer coating. Furthermore, the free carboxyl groups can be used to locally tune the swelling characteristics and transition temperature of the coatings. For the second technology, when Fe3O4 magnetic nanoparticles are integrated into PNIPAAm based composite systems, their resultant hyperthermia behavior becomes an ideal mechanism for remote controlled actuation. In this work, nano Fe3O4 octopods were seeded in fabricated PNIPAAm hydrogel micro-actuators. When the magnetic hydrogel structures were exposed to a magnetic field strength of 63 kA/m at a frequency of 300 kHz, the hydrogel micro-beams underwent a buckling effect when the field was absent and an unbuckling effect when the field was present. The hydrogel micro-beams were fabricated at an approximate distance from one another developing micromanipulating surfaces that were remote control activated. The response time, heating efficiency, and magnetic behavior were thoroughly studied. Lastly, micron sized polystyrene beads were exposed to the antifouling surfaces and movement of the beads was observed as the magnetic hydrogel micro-beams underwent their physical changes. For the third technology, a major reason of device failure in multi-chip module assemblies is a CTE mismatch between the underfill encapsulant material and the integrated circuit chip. Some of the failure mechanisms of microelectronic packaging due to CTE mismatch include fractures, delamination, or cracks through the device. In this section, the CTE of a commercially available underfill material is greatly reduced by loading the polymer resin material with hollow glass beads, to realize an overall effective CTE of 6.6 ppm/°C. Furthermore, the newly developed composite material exhibited outstanding thermomechanical stability at high temperatures beyond 150°C by holding a 3X lower CTE and a higher glass transition temperature.

Boronic acids are attractive synthetic intermediates and have been shown to be effective as inhibitors of various enzymes. In this project, the overarching goal is the selective inhibition of a protease present in the mitochondria known as human ClpXP. To study the potential selective inhibition of Human ClpXP using N-terminal peptidic boronic acid, we have designed a synthetic scheme that includes?-borylation of °,?-unsaturated carbonyl compounds using Cu(I) as catalyst, °-alkylation, saponification/hydrogenation, amidation, and oxidative removal of pinacolyl group with sodium periodate. A simple amidoboronic acid was also synthesized for stability studies. This compound, synthesized in 44% overall yield, could be used as a surrogate for N-terminal peptidic boronic acid to provide basic understanding of the stability of more elaborate N-terminal peptidic boronic acids. During the synthesis of this compound, published deprotection methods were not suitable to deprotect the pinacol group. A two-step protocol for pinacolyl boronic ester deprotection via a diethanolamine protected intermediate was successfully developed with the advantages of mild reaction conditions, tolerance to various functional groups, short reaction time and ease of product isolation. The current results will be useful for the deprotection of other boronic esters, such as pinanediol protected compounds, which are being used extensively in stereoselective synthesis. / Master of Science

Âncoras de glicosilfosfatidilinositol (GPI) são estruturas essenciais para a ancoragem de glicoconjugados e proteínas na superfície celular de protozoários. Trypanosoma cruzi produz uma gama de estruturas únicas de GPI, as quais ancoram mucinas e trans-sialidases, que participam de processos envolvidos na interação entre parasita e hospedeiro. Afim de estudar a biossíntese de âncora de GPI de T. cruzi e possivelmente utilizá-la como um potencial alvo anti-T.cruzi, este trabalho visa sintetizar análogos de âncoras de GPI e analisar o potencial destas moléculas como substratos da via biossintética de GPIs. Neste contexto, um pseudo-dissacarídeo 31 foi sintetizado através de O-glicosilação entre os doadores derivados de azido-glicopiranosídeo (32 ou 33a-d) e o acceptor de mio-inositol (34), preparados a partir de cloridrato de glucosamina (35) e metil-?-D-glucopiranósido (36), respectivamente, usando proteção/desproteção ortogonais. Cinco diferentes dadores de glicosídicos (32 e 33a-d) foram preparados para investigar a influcia dos seus grupos protetores na estereoselectividade da reações de O-glicosilação na presença de diferentes solventes para estudar o favorecimento da configuração ?, presente em GPIs. Ademais, a síntese do aceptor de mio-inositol 34 foi realizada em 12 etapas pela estratégia do rearranjo Ferrier para formar um derivado de ciclitol, além de diversas proteções/desproteções, funcionalizado que permite a introdução regiosselectiva da unidade de azido glicose (32-33a-d) e uma porção de fosfolípido no seu C-1 e posições C-6, respectivamente. Assim, O-glicosilação entre doador 33c e o acceptor 34, foi realizada utilizando TMSOTf como promotor para originar o composto 31c com boa estereoseletividade para ?, com elevado rendimento (~70%). Após a dealilação de 31c, a porção fosfodiéster contendo uma cadeia C-8 (87), preparada pela abordagem do H-fosfonato, foi anexada ao pseudo-dissacarídeo para gerar, após desprotecção global, o composto alvo 30a. A mesma estratégia sintética foi aplicada ao preparo do composto 91 contendo uma cadeia lateral alquil-naftil (90) que está em últmas etapas de desproteção para gerar o composto final 30c. Atualmente, o composto 30a está sendo testado como substrato da biossíntese de âncoras de GPI em membranas microssomais de Euglena gracilis, uma alga unicelular não patogênica, que pode potencialmente ser utilizada como modelo para parasitas humanos filogeneticamente relacionados. Após a incubação do potencial substrato de GPI 30a com membranas microssomais de E. gracilis para geração de metabólitos, será realizada análise do extrato por LC-MS e, eventualmente, isolamento dos produtos formados para posterior caracterização. Os produtos que apresentarem atividade como substrato ou como inibidores da biossíntese de GPI em E. gracilis serão também ensaiados na membrana microsomal do T. cruzi. / Glycosylphosphatidylinositol (GPI) anchors are essential molecules to attach glycoconjugates and proteins in protozoan\'s cell surface. Trypanosoma cruzi produces a range of unique GPI structures that anchor mucins and trans-sialidases which participate in important processes involved in the interaction between parasite and host. As an effort to study T. cruzi GPI anchor biosynthesis and possibly use it as a potential target for an antichagasic drug, this work aims to synthesize GPI anchor analogs (labelled or not) and analyze the potential of these molecules as substrates in the GPI biosynthetic pathway. In this context, a pseudo-disaccharide 31 was synthesized by O-glycosylation reaction between azide glycosyl donors (32 or 33a-d) and myo-inositol acceptor (34), prepared from glucosamine (35) hydrochloride and methyl ?-D-glucopyranoside (36), respectively, using orthogonal protection/ deprotection. Five different glycosyl donors (32 and 33a-d) were prepared to investigate the influence of their protective groups on the stereoselectivity of the O-glycosylation reaction in the presence of different solvents to afford the required GPI ?-linkage. In addition, the synthesis of the myo-inositol acceptor 34 was achieved using several protection/deprotection steps, besides the Ferrier rearrangement, to form a functionalized cyclitol derivative that enables the regioselective introduction of the azide glycoside unit and phospholipid moiety on its C-1 and C-6 positions, respectively. Then, O-glycosylation of acceptor 34 with donor 33c was accomplished in diethyl ether, using TMSOTf as promoter to give exclusively ?-anomer 31c in high yield. After deallylation of 31c, the phosphodiester moiety bearing an octyl chain (87), prepared by the H-phosphonate approach, was appended to the pseudo-disaccharide to yield, after deprotection, target compounds 30a. The same synthetic strategy was applied to the preparation of 30c, even though in the protective form, compound 91 bearing an alkyl-naphthyl side chain (90). Currently, compound 30a is being tested as substrates of GPI anchor biosynthesis in Euglena gracilis cell membranes, a non-pathogenic unicellular algae, which may potentially be used as a model for phylogenetically related human parasites. After incubation of the potential GPI substrate 30a with E. gracilis microsomal membranes for generation of metabolites, the analysis by LC-MS and, eventually, isolation of the products will be performed for further characterization. Products that show any substrate or inhibitory activities will be also assayed in T. cruzi microsomal membrane.

Submitted by Marilene Donadel (marilene.donadel@unioeste.br) on 2018-09-10T18:47:39Z No. of bitstreams: 1 Sonia_Silva_2018.pdf: 2515694 bytes, checksum: a478d4c4ee19f1a7d4f6782b4d90e96a (MD5) / Made available in DSpace on 2018-09-10T18:47:39Z (GMT). No. of bitstreams: 1 Sonia_Silva_2018.pdf: 2515694 bytes, checksum: a478d4c4ee19f1a7d4f6782b4d90e96a (MD5) Previous issue date: 2018-06-25 / The central theme of this research is old age, with emphasis on violence against the elderly and, in particular, financial violence. The problem that guided this research was: what are the elements and impacts of financial violence suffered by the elderly population in face of the contradictions and antagonisms produced by capitalist society? The objective of this research was to understand and analyze the elements and impacts of financial violence against elderly people assisted by the CREAS/CRAM of the municipality of Umuarama-PR, in the period of 2015 and 2016. Having as method of approach the scientific method, the research process was based on the qualitative, exploratory and bibliographical research, in the case study and in the documentary research by means of analysis in the assistance records for the elderly inserted in the CREAS/CRAM service, in the years 2015 and 2016. Based on the research, it was possible to identify that, in the delimited time frame, 190 cases of elderly people in situation of violation of rights were inserted, being that the universe of the research. From this universe, we identified that 27 cases of complaints received were of financial violence, however, when analyzing the records, we identified that the complaint proceeded in 18 of the cases. Thus, we have the sample of the research, that is, 18 assistance records for the elderly in situations of financial violence. After the analysis, as well as the study of authors investigating the subject matter, it was possible to verify the hypothesis formulated – financial violence against the elderly is the result of a capitalist culture present in contemporary social relations that are accentuated before a consumer culture, individuality and loss of the sense of the common good, leading to the fragility of the elderly's well-being – to answer the research problem. Research has shown that the hypothesis has been confirmed, since the analysis of the content indicates that financial violence against the elderly is intertwined with the capitalist system culture present in contemporary social relations. Therefore, the relationship of power and the scarcity of respect have their roots in capitalist culture, which generates social inequality and creates and recreates ideologies of individualism, selfishness, disrespect, consumerism, competitiveness and domination. / O tema central dessa pesquisa é a velhice, com ênfase na violência contra a pessoa idosa e, em particular, na violência financeira. O problema que orientou essa investigação foi: quais são os elementos e impactos da violência financeira sofrida pela população idosa diante das contradições e dos antagonismos produzidos pela sociedade capitalista? O problema que norteou essa pesquisa teve como objetivo geral compreender e analisar os elementos e impactos da violência financeira contra as pessoas idosas atendidas pelo CREAS/CRAM do Município de Umuarama-PR, no período de 2015 e 2016. Tendo como método de abordagem o método científico, o processo de investigação foi baseado na pesquisa qualitativa, exploratória e bibliográfica, no estudo de caso e na pesquisa documental por meio de análise nos prontuários de atendimentos à pessoa idosa, inseridos no Serviço CREAS/CRAM, nos anos 2015 e 2016. A partir da pesquisa, foi possível identificar que, no espaço temporal delimitado para pesquisa, foram inseridos 190 casos de pessoas idosas em situação de violação de direitos, sendo este o universo da pesquisa. Desse universo, identificamos que 27 casos de denúncias recebidas eram de violência financeira, contudo, ao analisar os prontuários, identificamos que a denúncia procedia em 18 dos casos. Chegamos, pois, a amostra da pesquisa, isto é, 18 prontuários de atendimento à pessoa idosa em situação de violência financeira. Após a análise, bem como o estudo de autores que investigam a temática em questão, foi possível realizar a verificação da hipótese formulada – a violência financeira contra a pessoa idosa é fruto de uma cultura capitalista presente nas relações sociais contemporâneas que se acentuam diante de uma cultura de consumo, da individualidade e da perda do senso do bem comum, levando à fragilidade do bem-estar da pessoa idosa – para responder ao problema da pesquisa. A investigação nos mostrou que a hipótese foi confirmada, pois a análise do conteúdo apreendido aponta que a violência financeira contra a pessoa idosa está interligada à cultura do sistema capitalista presente nas relações sociais contemporâneas. Assim, a relação de poder e a escassez de respeito têm suas raízes na cultura capitalista, que gera a desigualdade social e constrói e reconstrói ideologias de individualismo, egoísmo, desrespeito, consumismo, competitividade e dominação.

The thesis entitled ‘Chemistry of molybdenum xanthate (MoO2[Et2NCS2]2): Applications in organic synthesis’ is presented in 4 chapters. Molybdenum (IV and VI) oxo-complexes are the subject of significant interest due to their functional and structural similarities with several molybdo-enzymes.1 Literature survey suggests that, molybdenum (VI as well as IV) xanthate2 1 resembles the active sites of various molybdo-enzymes. Therefore, in the present thesis, we are presenting our attempts directed towards exploiting molybdenum xanthate 1 in developing various useful methodologies. Figure 1: Molybdenum xanthate Chapter 1 discloses the utility of molybdenum xanthate (1) in catalytic, aerobic oxidation of organic azides and alcohols as presented in part A and B. Part A: A mild molybdenum xanthate catalyzed, chemoselective oxidation of benzylic azides to the corresponding aldehydes3 under aerobic condition is described. This oxidation turned out to be a general method and a variety of benzylic azides were oxidized to the corresponding aldehydes. This oxidation protocol tolerates a variety of functional groups including alcohols, esters, ketones, halides and olefins. More importantly, the oxidation of azides stops at corresponding aldehyde stage without further oxidation to the corresponding carboxylic acids. A few examples are presented in scheme 1. Part B: As our attempts to oxidize alcohols with molybdenum xanthate 1 were unsuccessful (Chapter 1, Part A), we have attempted supporting the reagent 1 and investigated its utility in the oxidation of alcohols. As a consequence, polyaniline supported molybdenum xanthate (MoO2[Et2NCS2]2) is designed and used in an aerobic and mild chemoselective oxidation of alcohols4 to the corresponding aldehydes and ketones. The scheme to use polyaniline as the support for molybdenum xanthate was derived from the fact that polyaniline is known to increase the redox activity of various metal complexes by coordinating to the metal centre.5 The present oxidation strategy tolerates a variety of functional groups such as olefin, ketones, sulfides, tertiary amines, propargyl group etc. This oxidation strategy also works very well for the oxidation of secondary benzylic alcohols. Interestingly, the supported catalyst can be filtered after the reaction and reused for further oxidation without loss of its activity. Some representative examples are presented in Scheme 2. Chapter 2 describes the chemoselective and efficient reduction of azides to the corresponding amines. In this chapter, we have shown that a catalytic amount of molybdenum xanthate (1, MoO2[S2CNEt2]2) with PhSiH3 is an effective catalyst for the reduction of azides to the corresponding amines.6 This reduction of azides by 1, was inspired by the reductive silylation of aldehydes through the activation of silanes.7 This reduction tolerates a variety of reducible functional groups such as olefin, aldehydes, ketones, esters, amides and ethers, acetals etc. This strategy was also extended to various aliphatic azides to synthesize amine and their N-Boc derivatives in good yields. Scheme 3 illustrates few examples. Chapter 3 discloses convenient methods for the synthesis of substituted thiourea derivatives as presented in part A and B. Part A: A convenient method for the synthesis of tri-substituted thiourea derivatives by the reaction of primary amines with molybdenum dialkyl dithiocarbamates is presented in Part A.8 Primary amines on reaction with molybdenum xanthate produce corresponding thioureas in moderate to good yields. Similar reactions with propargylamine and 2-aminoethanol produce cyclic thiaoxazolidine and oxazolidine derivatives respectively. This methodology has been successfully adopted for the synthesis of amino acids derived chiral thioureas. Some examples are presented in Scheme 4. Scheme 4: Molybdenum xanthate mediated synthesis of thioureas Part B: An efficient method for the synthesis of symmetrical and unsymmetrical substituted thiourea9 derivatives by simple condensation of amine and carbon disulfide in aqueous medium is extensively studied. Present method describes the involvement of amino dithiol moiety as an intermediate. Though this method is not successful with secondary amines and aryl amines, it works smoothly with aliphatic primary amines to afford various di- and tri-substituted thiourea derivatives. The present method is also useful in synthesizing various substituted 2-mercapto imidazole heterocycles in moderate yields. A few examples are seen in Scheme 5. Scheme 5: Synthesis of thiourea derivatives in aqueous medium Chapter 4 describes a chemoselective deprotection10 of terminal acetonides (isopropylidines) by using aqueous TBHP (70%). A variety of acetonide derivatives on reaction with aq. TBHP in water:t-BuOH (1:1) as solvent mixtures furnish the corresponding acetonide deprotected diol products in good yields. This unprecedented deprotection strategy, tolerates a variety of acid sensitive functional groups such as silyl ether, trityl, olefin, propargyl, methoxymethyl ether, N-Boc, lactones, esters etc. A few examples are documented in Scheme 6. Scheme 6: Chemoselective deprotection of acetonides (For structural formula pl see the pdf file)

Orientador: Adriana Giaqueto Jacinto / Resumo: Trazer à tona discussões e reflexões em torno da reiteração das práticas infracionais configura-se como um grande desafio, já que de um lado nos deparamos com o crescente discurso burguês de combate à criminalidade, alinhado à ideologia neoliberal, cujos pressupostos se fortalecem pela lógica tutelar, moralista e segregacionista em relação aos adolescentes e jovens que cometem atos infracionais. Na outra ponta, nas fronteiras da subalternidade, situam-se meninos e meninas, que estereotipados pela periculosidade e pela identidade marginal, experimentam os mais perversos impactos da violação de direitos e da (des) proteção social. Sendo assim, o presente estudo tem por objetivos investigar a reiteração do ato infracional, na perspectiva do adolescente\jovem, na sociedade de classes; analisar os rebatimentos do modo de produção capitalista na trajetória de vida dos adolescentes\jovem bem como contextualizar as políticas sociais de proteção à infância e juventude e como essas atuam na efetivação dos direitos sociais. O estudo pauta-se no método do materialismo histórico dialético, sendo a abordagem qualitativa o desenho metodológico adotado. Além da pesquisa bibliográfica, o estudo contempla também a pesquisa documental realizada em autos judiciais, a qual possibilitou uma aproximação aos discursos e posicionamentos políticos-ideológicos dos operadores do sociojurídicos que se situam entre a lógica da responsabilização penal e da punição. Já a pesquisa empírica adota a História O... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Bringing up discussions and reflections on the reiteration infractions of is a major challenge, since on one hand we are faced with the growing bourgeois discourse to fight crime, aligned with the neoliberal ideology, whose assumptions are strengthened by the tutelary, moralistic and segregationist logic in relation to adolescents and young people who commit infractions. At the other end, at the borders of subalternity, are boys and girls, who are stereotyped by dangerousness and marginal identity, experience the most perverse impacts of violation of rights and social deprotection. Thus, the present study aims to investigate the reiteration of the infraction, from the perspective of the adolescent \ youth, in the class society; to analyze the repercussions of the capitalist mode of production in the life trajectory of adolescents and yonug youth as well as to contextualize the social policies for the protection of children and youth and how they act in the realization of social rights. The study is based on the method of dialectical historical materialism, with the qualitative approach being the methodological design adopted. In addition to bibliographic research, the study also contemplates documentary research carried out in court records, which allowed an approximation to the speeches and political-ideological positions of socio-legal operators that are situated between the logic of criminal accountability and punishment. Empirical research, on the other hand, adopts Oral ... (Complete abstract click electronic access below) / Resumen: Plantear debates y reflexiones sobre la reiteración de las prácticas de infracción es un gran desafío, ya que, por un lado, nos enfrentamos con el creciente discurso burgués para combatir el crimen, alineado con la ideología neoliberal, cuyos supuestos se fortalecen con la lógica tutelar, moralistas y segregacionistas en relación con adolescentes y jóvenes que cometen infracciones. En el otro extremo, en las fronteras de la subordinación, se encuentran los niños y niñas, que son estereotipados por el peligro y la identidad marginal, experimentando los impactos más perversos de la violación de los derechos y la (des) protección social. Por lo tanto, el presente estudio tiene como objetivo investigar la reiteración de la infracción, desde la perspectiva de los adolescentes / jóvenes, en la sociedad de clases; analizar las repercusiones del modo de producción capitalista en la trayectoria de la vida de los adolescentes y jóvenes, así como contextualizar las políticas sociales para la protección de niños y jóvenes y cómo actúan en la realización de los derechos sociales. El estudio se basa en el método del materialismo histórico dialéctico, siendo el enfoque cualitativo el diseño metodológico adoptado. Además de la investigación bibliográfica, el estudio también contempla la investigación documental realizada en los registros judiciales, que permitió una aproximación a los discursos y las posiciones político-ideológicas de los operadores socio-legales que se encuentran entre la l... (Resumen completo clicar acceso eletrônico abajo) / Doutor

Ce travail décrit la synthèse et l’étude conformationnelle de nouveaux oligomères mixtes. Dans le premier chapitre, en exploitant des travaux antérieurs concernant la synthèse des N-aminodipeptides, nous avons obtenu des oligomères mixtes, alternant des liens amides et N-aminoamides nommés [[allpha]/[alpha]-N-amino]mères. L’oligomérisation des N-aminopeptides en phase liquide est réalisable grâce à un couplage au fluorure d’acide à partir d’une unité de base possédant les protections Boc (extrémité N-terminale), Bn (extrémité C-terminale) et phtaloyle (azote latéral). Le deuxième chapitre présente les résultats obtenus par différentes méthodes spectroscopiques (RMN, IR et DC) et modélisation moléculaire sur les différents oligomères synthétisés dans le chapitre 1. Ces travaux ont permis de mettre en évidence un repliement répétitif original par une liaison hydrogène de type C8 impliquant un groupement carbonyle du phtalimide et un proton amidique / This work describes the synthesis and the conformational study of new mixed oligomers. In the first chapter, using previous work on the synthesis of N-aminodipeptids, we were obtained mixed oligomers alternating amid and N-aminoamid bond named [[alpha]/[alpha]-N-amino]mers. The oligomerization of N-aminopeptids in liquid phase was achieved through an acid fluorid coupling from a building block with the protections Boc (N-terminus), Bn (C-terminus) and phtaloyl (N-side). The second chapter presents the results obtained by different conformational spectroscopic methods (NMR, IR and DC) and molecular modeling on the various oligomers synthesized in Chapter 1. This work has allowed to highlight a original repetitive folding by a C8 hydrogen bond involving the carbonyl group of phthalimid and a amid proton

Made available in DSpace on 2016-04-29T14:16:17Z (GMT). No. of bitstreams: 1 Loana Rios Andrade Lima Bartolotti.pdf: 7292119 bytes, checksum: 78f2ea4114d00cb3c6cc026f96e744a3 (MD5) Previous issue date: 2012-10-04 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study has as objective to analyze the impact of Varig's bankruptcy for the laid off and retired people from that company in their conditions of existence, focusing on the impacts of layoffs and loss of rights with the intervention of Aerus. It examines the consequences of a financial lawsuit which withdrew the rights of social protection of workers from that company. It deals with the creation and collapse of Varig company established in 1927, emphasizing the Ruben Berta Foundation and the Aerus pension fund. The historical reconstruction of the company by means of documents and bibliographies is enriched by interviews. It makes use of oral history to characterize the transformations in the everyday life of workers and their families from bankruptcy. There are thirty-two testimonies collected in this research that aggregate eighteen laid off workers and fourteen retired ones who occupied different positions in the company for over 15 years. The company's bankruptcy in July 2006 had an impact not only on their employees, but on much of the national society and was part of a process of changing the standard operation of Brazilian transportation airlines. Among the main causes of the bankruptcy of Varig, the following stand out: the exhaustion of the management of a national airline company of transportation that, although of quality, was placed in conflict with the interests of the economic and political situation of the country coupled with the lack of interest from the government to maintain that model of business management. Since the "hard landing" of Varig, their laid off and retired workers still struggle and hope for a future that brings back their dignity consistent with their story of hard work and dedication to the great airline company / Este estudo tem por objetivo analisar o impacto da falência da Varig, para os demitidos e aposentados dessa empresa, nas suas condições de existência, enfocando as demissões e perdas de direitos com a intervenção no Fundo de Pensão Complementar Aerus. Examina as sequelas de um processo jurídicofinanceiro que retirou direitos de proteção social dos trabalhadores daquela empresa. Ocupa-se da criação e falência da empresa Varig, criada em 1927, dando ênfase à Fundação Ruben Berta (FRB) e ao Aerus. A reconstrução histórica da empresa, feita por meio de documentos e bibliografias, é enriquecida por depoimentos. Vale-se da história oral para caracterizar as transformações ocorridas no cotidiano de vida dos trabalhadores e de suas famílias a partir da falência da empresa. São 32 depoimentos colhidos na pesquisa, que agregam 18 trabalhadores demitidos e 14 aposentados, que ocuparam diferentes cargos na empresa ao longo de mais de 15 anos. A falência da empresa, em julho de 2006, causou impacto não somente em seus funcionários, mas em grande parte da sociedade nacional e fez parte de um processo que alterou o padrão operacional da viação aérea brasileira. Dentre as causas principais de falência da Varig, destaca-se o esgotamento do modelo de gestão da empresa nacional de viação aérea que, embora de qualidade, se colocava em confronto com os interesses da conjuntura econômico-política do País, somada à ausência de interesse do governo em manter aquele modelo de gestão empresarial. Desde o pouso forçado da Varig, seus trabalhadores, demitidos e aposentados, ainda lutam e esperam por um futuro que faça retornar a dignidade compatível com sua história de trabalho e dedicação à grande empresa aérea

Les Héparanes sulfates (HS) appartiennent à la famille des glycosaminoglycanes (GAGs) qui sont des polysaccharides existants sur la surface cellulaire ou dans la matrice extracellulaire des cellules animales. Les GAGs jouent des rôles essentiels dans plusieurs processus biologiques via leurs interactions avec certaines protéines (chemokines, cytokines, facteurs de croissance, enzymes…) dont ils modulent les activités biologiques. Ils sont constitués par la répétition d’un motif disaccharidique de base comportant un acide uronique lié à un 2-amino-sucre. Une diversité moléculaire considérable provient de l’existence de divers motifs de O-et/ou N-sulfatation ainsi que de motifs d’épimérisation au niveau de l’acide uronique. Cette diversité qui est responsable d’interactions spécifiques de haute affinité avec différentes protéines serait due à l’action des différentes enzymes de biosynthèse. Ce travail de thèse vise à développer de nouvelles méthodologies nécessaires à la préparation d’une chimiothèque octasaccharidique de fragments d’HS, dans le but d’étudier la spécificité des enzymes de biosynthèse des HS et principalement la N-déacétylase N-sulfotransférase (NDST) et la C-5 épimérase. La chimiothèque octasaccharidique peut être obtenue à partir d’un seul octasaccharide dont les quatre atomes d’azote seraient protégés par des groupements protecteurs différents (octasaccharide « N-différencié »). La synthèse de cet octasaccharide constitue notre objectif principal.Nous nous sommes intéressés dans un premier temps à l’optimisation de la synthèse d’une brique disaccharidique impliquée dans la synthèse des fragments d’héparane sulfate. Dans cet objectif nous avons mis au point une méthode d’acétylation sélective de l’hydroxyle primaire, une méthode de benzylation compatible avec la présence à l’acétate et une procédure « one-pot » comportant quatre étapes de synthèse du disaccharide et facilitant l’accès au disaccharide avec 45 % de rendement global.Par la suite, nous avons optimisé la réaction de glycosylation entre les briques disaccharidiques en utilisant le donneur N-phényltrifluoroacétimidate, dans le but d’avoir une stéréosélectivité α maximale et d’améliorer le rendement de glycosylation. Les conditions optimisées ont permis l’accès au tétrasaccharide et à l’octasaccharide ayant les fonctions amines sous forme de groupements azido, avec un excellent rendement (95 %) et une bonne stéréosélectivité (96/4) en faveur de l’anomère α et sont reproductibles à grande échelle. La troisième partie était consacrée à une étude méthodologique afin de permettre la synthèse de l’octasaccharide « N-différencié » précurseur de la chimiothèque octasaccharidique. Dans ce but, nous avons choisi les groupements Fmoc, Alloc, pNZ et N3 comme groupements protecteurs des fonctions amines de l’octasaccharide. Nous avons préparé différents accepteurs ayant les fonctions amines protégées avec ces groupements afin d’étudier l’influence des différents groupements N-protecteurs de la fonction amine de l’accepteur sur la réaction de glycosylation. Les différents tétrasaccharides ont été obtenus avec d’excellents rendements (87–97 %) et une bonne stéréosélectivité (autour de 95/5 en faveur de l’anomère α). Enfin, nous avons effectué une étude de l’orthogonalité de la déprotection de ces groupements protecteurs (N3, Alloc, Fmoc et pNZ). Cette étude est essentielle avant la préparation de l’octasaccharide pour prouver la stratégie de la synthèse. En plus cette étude facilitera la préparation de la chimiothèque octasaccharidique une fois l’octasaccharide « N-différencié » préparé. / Heparan sulfate (HS), a highly sulfated glycosaminoglycan present in the extracellular matrix and at the cell surface, is known to play vital functional roles in various biological processes due to its interactions with proteins (chemokines, cytokines, growth factors, enzymes ...). HS consist of a repeating disaccharide unit, composed of a glucosamine and a hexuronic acid (glucuronic acid or its C5 epimer, iduronic acid).The HS chains are further modified by some epimerases and sulfotransferases during their biosynthesis. These sulfation/epimerization patterns provide considerable complexity. These modifications are required for interaction with many protein ligands.This thesis aims to develop new methodologies for the preparation of a library of octasaccharides, HS fragments, in order to study the specificity of HS biosynthesis enzymes, mainly N-deacetylase N-sulfotransferase (NDST) and the C-5 epimerase. The library can be obtained starting from a single octasaccharide whose four nitrogen atoms are protected by various protecting groups (octasaccharide N-differentiated). The synthesis of this octasaccharide is our main goal.We are interested in first to optimize the synthesis of a fully protected disaccharide which is used as building block in our heparan sulfate fragments synthesis. For this purpose we have developed a regioselective acetylation method of a disaccharide bearing three hydroxyl groups using a temporary protection, a benzylation method compatible with the presence of one acetate group using silver oxide and a one-pot procedure incorporating up to four steps, reducing work-up and time-consuming purifications. In the second chapter, we optimized the glycosylation reaction between two disaccharides using the N- phényltrifluoroacétimidate donor in order to have good α stereoselectivity and yield. We are now able to obtain the tetrasaccharide and the octasaccharide with 95 % yield and (α/β : 96/4) stereoselectivity.The third part was devoted to the methodological study to obtain the N-differentiated octasaccharide, precursor of a octasaccharides library. For this purpose, we chose Fmoc, Alloc, pNZ and N3 as protecting groups of the amine groups. We have prepared various acceptors with these different protecting groups in order to study them in glycosylation reactions. The tetrasaccharides were obtained with excellent yields (87-97%) and good stereoselectivity (around 95/5 for the α anomer) with the four protecting groups. Finally, we conducted a study to deprotect these protecting groups (N3, Alloc, Fmoc and pNZ) on the tetrasaccharides. This study is essential before preparing the octasaccharide as a proof of the synthesis strategy. In addition this study will facilitate the preparation of the octasaccharides library once the N-differentiated octasaccharide prepared.