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La variante « glyoxylique » de la réaction de Perkin permet de lier entre eux deux fragments aromatiques par un pont maléique. La rigidification de cet intermédiaire flexible mène à des systèmes aromatiques polycycliques étendus par création des liaisons carbone-carbone manquantes. Cette stratégie requiert l'utilisation d'acides arylacétiques et arylglyoxyliques, et l’utilisation d'unités bifonctionnelles a auparavant permis la synthèse de cibles variées allant des phénacènes plans aux (poly)hélicènes très distordus, mais aussi des macrocycles conjugués. Afin d'étendre la taille et la variété des molécules obtenues à l'aide de cette stratégie, des méthodes générales de protection/déprotection sont développées. Une dissymétrisation efficace des unités bifonctionnelles mène à des nouveaux précurseurs monoprotégés qui sont ensuite assemblés par la réaction de Perkin en oligomères de taille contrôlée possédant encore des fonctions chimiques réactives aux extrémités après déprotection. L'utilisation de ces derniers lors d'une deuxième réaction de Perkin donne alors accès à de longs précurseurs flexibles, d’au moins cinq unités, qui donneront ensuite de très longs phénacènes, de grands macrocycles mais aussi des cyclo-tris[5]hélicènes qui présentent une géométrie de Möbius persistante et une aromaticité de Möbius. / The “glyoxylic” variant of the Perkin reaction allows to link two aromatic fragments by a maleic bridge. The stiffening of the obtained flexible intermediate by the creation of the missing carbon-carbon bonds leads to extended polycyclic aromatic systems. This strategy relies on the use of arylacetic and arylglyoxylic acids, and the use of bifunctional units has previously allowed the synthesis of a variety of targets spanning from flat phenacenes to strongly distorted (poly)helicenes, as well as of conjugated macrocycles. This approach is generalized here by developing protection/deprotection techniques in order to enhance the size and the variety of the molecules that can be obtained by this strategy. These techniques enable an efficient dissymetrization of bifunctional units and the recycling of symmetrical side products. The new monoprotected building blocks are connected by Perkin reactions to yield oligomeric intermediates with reactive functions at their extremities after deprotection. Several of these intermediates are assembled in a second Perkin reaction to obtain long phenacenes, large macrocycles and also cyclo-tris[5]helicenes with persistent Möbius geometry and Möbius aromaticity.

Les IDE sont au cœur de la mondialisation et des rapports Economiques Nord-Sud. La question de leur protection et de leur régulation juridique se pose avec acuité. Devant la rareté des autres sources de financement du développement et d’accès à la technologie, l'IDE constitue une source importante pour combler l'insuffisances des ressources internes. raison pour laquelle, les pays d'Afrique de l'ouest se livrent à une concurrence farouche pour les accueillir. Dans la sous région ouest africaine le droit et la réglementation sont utilisés comme des instruments importants pour mesurer l'attractivité et la sécurité juridiques des pays. Le sujet s'interroge, analyse la dimension sécuritaire(traitement et garantie) a t'elle permise une plus grande promotion et d'accueil des IDE?. Notre sujet tentera d'analyser et situer l'effectivité du régime juridique des investissements étrangers au plan interne( codes des investissements, codes miniers et codes pétroliers). Mais aussi au plan externe( Traité bilatéraux d'investissement TBI,conventions sectoriels de protection arbitrage et garantie). Le dernier axe de ce travail de recherche, est le phénomène de la Communautarisation de la protection avec les tentatives d'harmonisation et d'uniformisation des réglementations nationales en Afrique de l'Ouest. Le dernier aspect, c'est l'institutionnalisation à travers les Organisations Economique Internationales (Banque Mondiale et Banque Africaine de développement BAD) du système juridique de protection en Afrique de l'Ouest. / "The protection of foreign direct investment in developing countries: the example of West Africa"FDI is at the heart of globalization and north-south economic relations. The question of their protection and legal regulation is acute. Faced with the scarcity of other sources of development finance (development aid) and the difficulties of access to technology, FDI is an important resource for filling the insufficiency of internal resources. This is why African countries in general, and those in West Africa in particular, are competing vigorously to receive foreign capital by providing them with an attractive, secure and non-discriminatory legal and institutional framework. Indeed, in the West African subregion, the law is used by States, but also by subregional integration organizations such as ECOWAS as an important instrument for demonstrating economic attractiveness. Thus, the analysis and measurement of the legal and institutional framework for FDI in West Africa will be discussed. In other words, has the security dimension of the investment (reception, processing, guarantee and settlement of disputes etc.) allowed for greater promotion and reception of investments from these countries?The interest of the subject is multiple. Indeed, at the legal and academic level, it allows to know, analyze and situate the entire legal regime of foreign investment at the internal level (investment code, mining code, oil code). At the external level, there is a multitude of conventions - such as bilateral BIT investment treaties -, accession to the relevant international investment conventions, and of course the increasingly visible and visible role of Community law in through the "communitisation of the law of foreign direct investment". The study of this subject shows the deep gap that exists between theory and practice in the FDI legislation of the countries of this part of Africa. If, upstream, the texts are more or less similar to those of the advanced countries, downstream, the execution of the texts by the public administrations makes mediocre the environment and the practice of the businesses. This theme on the legal protection of investments raises other questions and issues such as: the intervention of more and more actors and the instruments negotiated within them (World Bank, ADB, WTO, OECD, ECOWAS and UEMOA). etc.). There are also new issues related to environmental issues, corporate social responsibility and heritage issues. Finally, the problems posed by new types of investment, particularly PPP public-private partnerships, will be studied. The current nature of the research is striking, as there are several issues related to investment protection in countries such as West Africa. It is about the transfer of technology in a new context, the industrialization by the natural resources, the contribution on the development of the host country and the creation of jobs especially in an international context where Africa became again attractive.

Les héparanes sulfates (HS) sont des polysaccharides linéaires et sulfatés exprimés sur la surface cellulaire où ils interagissent et régulent l’activité de nombreuses proteines, en particulier les cytokines et chimiokines. Ils sont à ce titre de bons candidats médicaments dans des pathologies inflammatoires, autoimmunes ou en oncologie. L’unité répétitive de ce biopolymère est constituée d’un résidu de D-glucosamine lié à un acide uronique par une liaison 1,2-cis. Malheureusement, la formation d’un glycoside 1,2-cis dans la série 2-azido-2-déoxy-D-glucose avec une haute stéréosélectivité reste un des plus grands défis de la glycochimie. Parmi les nombreuses méthodologies permettant d’accéder à la synthèse des fragments d’HS avec de bons rendements et une bonne stéréosélectivité, nous avons été particulièrement intéressés par l’assistance anchimérique d’un groupement protecteur en position 6 du donneur. L’objectif de ce travail était de trouver des groupements protecteurs qui favoriseront la stéréosélectivité 1,2-cis. Nous avons préparés plusieurs donneurs thioglycosides modifiés en position 6 par des différents groupements protecteurs. L’activation des thioglycosides passe par une étape de formation des triflates anomériques. Nous avons élaboré un protocole de suivi de l’activation sur un donneur modèle afin de suivre la formation du triflate anomérique, sa plage de stabilité, ses produits de dégradation ainsi que les produits secondaires d’activation par RMN à basse température. Ensuite, ce protocole d’activation a été utilisé avec tous les donneurs synthétisés afin d’ajuster les conditions de glycosylation. Les tests de glycosylation nous ont permis de décéler plusieurs groupes capables de favoriser la stéréosélectivité 1,2-cis. Certains groupements protecteurs ont manifesté une incompatibilité avec les conditions d’activation des thioglycosides. Pour contourner ce problème, nous avons remplacé les thioglycosides par les donneurs N-phényltrifluoroacétimidates. Après avoir effectué des études d’activation sur ces donneurs toujours par RMN à basse température, les glycosylations ont été effectuées. Finalement, les groupements protecteurs favorisant la stéréosélectivité 1,2-cis ont été testés dans différentes conditions de déprotection afin d’établir la compatibilité de ces groupements protecteurs avec les conditions de synthèse des oligosaccharides d’HS. / Heparin sulfate (HS) are linear and sulfated polysaccharides present at the cell surface. HS interact and regulate activity of numerous proteins, especially cytokines and chemokines. Therefore, HS oligosaccharides are targeted as potential drugs in inflammation, autoimmune disease or tumor treatment. The basic disaccharide unit of HS consists in D-glucosamine residue linked to an uronic acid by 1,2-cis glycosidic linkage. Unfortunately, the formation of highly stereoselective 1,2-cis glycosidic bond in 2-azido-2-deoxy-D-glucose series is still a major concern in glycochemistry. Amongst the numerous methodologies favoring the stereoselective 1,2-cis linkage formation, we were particularly interested in 6-O-anchimeric assistance. Several thioglycoside donors with different protecting groups in position 6 were prepared to find some 1,2-cis stereodirecting protecting groups. Some thioglycoside activation related in literature yields a reactive anomeric triflate intermediate. In order to observe its formation and to determine the limits of its stability and by-product formation, a new low temperature NMR experiment protocol was elaborated. All synthesized donors were tested using this protocol in order to adjust their glycosylation conditions. The glycosylation tests revealed several 1,2-cis stereodirecting protecting groups. Since certain protecting groups were incompatible with thioglycoside activation conditions, corresponding NPTFA donors were used as an alternative. Their activations were monitored by low temperature NMR techniques and followed by their glycosylations. Finally, all 1,2-cis stereodirecting protecting groups were tested in different deprotection conditions to determine the compatibility of chosen protecting groups with our HS oligosaccharide design synthesis.

Made available in DSpace on 2016-03-15T19:48:17Z (GMT). No. of bitstreams: 1 Claudio Jose Alves Viana.pdf: 948026 bytes, checksum: d140a8bb99cc4ac14b1c3170f3cc8604 (MD5) Previous issue date: 2012-02-14 / The history of the conflict among the city of Mossoró and the cangaceiros that tried to assault it in 1927 offered a starting point for the investigation of the constituent elements of their religiosities presented in this study. We tried to investigate the religiosity of the city, as part of the official Catholicism, and of the cangaceiros , as popular religiosity, for visualize the social relationship among them. For so much, we studied the origin and the development of the city of Mossoró as social consequence of the religion and, in the sequence, we tried to verify as the cangaço appeared and grew in the society, besides understanding its religious practice in the relationship with its compound world. We verified that different characters thieves, common men and authorities maintained religious trust in front of the armed danger; in other words, the mystic of the rites operated externally to the imaginary forces, constituting mental operations to face the enemies. Finally, the research approaches the current relationship of the city with the cangaço and, mainly, it verifies which reasons are took to consider Jararaca a saint of the popular religiosity. / A história do conflito entre a cidade de Mossoró e os cangaceiros que tentaram assaltá-la em1927 ofereceu um ponto de partida para a investigação dos elementos constitutivos de suas religiosidades apresentada neste estudo. Procuramos investigar a religiosidade da cidade, como parte do catolicismo oficial, e dos cangaceiros, como religiosidade popular, para, assim, visualizar a relação social entre elas. Para tanto, estudamos a origem e o desenvolvimento da cidade de Mossoró como decorrência social da religião e, na sequência, procuramos verificar como o cangaço surgiu e se desenvolveu na sociedade, além de entender a sua prática religiosa na relação com o seu complexo mundo. Verificamos que personagens diferentes bandidos, homens comuns e autoridades mantinham confiança religiosa frente ao perigo armado; em outras palavras, a mística dos ritos operava externamente às forças imaginárias, constituindo operações mentais para o enfrentamento dos inimigos. Por fim, a pesquisa procura abordar a relação dos dias atuais da cidade com o cangaço e, principalmente, verificar quais as razões que levaram a considerar o cangaceiro Jararaca santo da religiosidade popular.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

Inhibiting protein-protein interactions to achieve a therapeutically desired effect has been a goal in the field of drug discovery for decades. Recently, advances in peptidomimetics have led researches to the use of cyclized peptides to achieve this goal. Cyclization of linear peptides restricts the number of conformations of the peptide, increasing the peptide's affinity to binding to the desired target. Cyclization also stabilizes the peptide, allowing the peptide to be resistant to proteases. This study explores the optimization of solution phase synthesis of an important integrin-mediated cell adhesion cyclic peptide for the therapeutic inhibition of multiple myeloma, cHYD1. cHYD1 was originally synthesized via solid phase peptide synthesis, and the need for a scaled up synthesis version was needed after positive bioactivity results were obtained. Chapter 3 includes the molecular modeling exploration of a possible new mechanism to which cyclized peptides could work, in which, rather than a recognition and non-recognition strand being implemented, a specific directional face is used for protein-protein interaction. This was done with the implementation of an antagonistic cyclic peptide to replace human growth hormone in its interaction with the human growth hormone receptor, and the subsequent di-cyclic peptide agonist.