Este trabalho teve como objetivo a síntese e a caracterização de bases de Schiff biopoliméricas e alguns de seus complexos metálicos formados a partir do biopolímero quitosana. Na primeira etapa do trabalho foram utilizados o salicilaldeído e seus derivados, 5-metóxisalicilaldeído e 5-nitrosalicilaldeído para produzir as bases de Schiff biopoliméricas com a quitosana (GD = 90,4 %, Mw =223 kDa), as quais foram utilizadas para a síntese dos complexos de Zn(II), Pd(II) e Pt(II). Na segunda etapa, bases de Schiff biopoliméricas anfifílicas foram sintetizadas utilizando as quitosanas (GD = 90,4 e 89%, Mw = 223 e 64 kDa), e o grupo hidrofóbico salicilaldeído bem como o grupo hidrofílico 2,3-epóxi-1-propanol (glicidol). E esses ligantes também foram utilizados para complexar os metais Zn(II), Pd(II) e Pt(II). As bases de Schiff biopoliméricas anfifílicas foram sintetizadas a fim de se avaliar o efeito da presença do grupo hidrofílico glicidol e também o da variação dos valores de Mw nas propriedades físico-químicas e biológicas. Todos os compostos sintetizados foram caracterizados por espectroscopia (1H-RMN, FTIR, DRX, UV-Vis), análise térmica (TG/DTG-DTA) e microscopia (MEV-EDX). Afim de se avaliar a atividade biológica das bases de Schiff biopoliméricas e seus complexos foram utilizados dois agentes patógenos de plantas: a bactéria Gram-negativa Pseudomonas syringae pv. tomato e o fungo de cerais Fusarium graminearum. Os resultados obtidos demostraram que tanto as bases de Schiff biopoliméricas quanto seus complexos exibiram atividade antibacteriana significante.  Entretanto, o potencial antifúngico das bases de Schiff foi melhor que para alguns complexos, devido a diferença morfológica relacionada a constituição da membrana celular externa e da parede celular dos microrganismos testados. Portanto, foi observado que a morfologia é um fator diretamente relacionado aos mecanismos de ação. A avaliação da citotoxicidade foi realizada in vitro contra células de carcinoma de mama MCF-7 por ensaio de MTT. Os resultados de citotoxicidade obtidos demonstraram que todos os compostos apresentaram uma diminuição na percentagem da viabilidade celular, em função da concentração. Observou-se para as bases de Schiff biopoliméricas uma atividade antitumoral mais efetiva que para as quitosanas sem modificação. Em baixas concentrações dos complexos, observou-se uma baixa inibição celular, especialmente para os complexos de zinco. Porém, em concentrações mais elevadas, foi verificado um aumento significativo da toxicidade. Portanto, a principal contribuição esperada deste trabalho foi a síntese, caracterização e estudo desses novos compostos de bases de Schiff biopoliméricas e dos biocomplexos, com potencial para atuar em aplicações biológicas. / Biopolymeric Schiff bases prepared from chitosan and some of their complexes were synthesized, characterized and evaluated regarding their biological activity. In a first step, salicylaldehyde, 5-methoxysalicylaldehyde and 5-nitrosalicylaldehyde were used to synthesize biopolymeric Schiff bases with chitosan (GD = 90.4 %, Mw =223 kDa), as well as their Zn(II), Pd(II) and Pt(II) complexes. In a second stage, amphiphilic biopolymeric Schiff bases were prepared from two different chitosans (GD = 90.4 and 89%, Mw = 223 e 64 kDa), but introducing the salicylaldehyde hydrophobic group and also 2,3-epoxy-1-propanol (glycidol) hydrophilic group. Zn(II), Pd(II) and Pt(II) complexes where prepared from such amphiphilic biopolimeric ligands. All these ligands and respective complexes were obtained in order to evaluate the effect of increased solubility caused by glycidol the hydrophilic group and as well as the different Mw values in physical chemical and biological properties. Thus different spectroscopic (1H-NMR, FTIR, XRD, UV-Vis), thermal analytical (TG/DTG-DTA) and microscopy (MEV-EDX) techniques were used to characterize all the compounds. The biological activity was evaluated against two economically important plant pathogens, Gram-negative bacteria Pseudomonas syringae pv. tomato and Fusarium graminearum cereal fungus. In general, the results demonstrated that biopolymer Schiff bases and their complexes exhibited significant antibacterial activity. However, the antifungal potential of the Schiff bases was better than for some complexes, due to the morphological difference related to the constitution of the cell membrane and cell wall of the tested microorganisms. Therefore, it was observed that morphology is a factor directly related to the mechanisms of action. Cytotoxicity was evaluated in vitro against breast cancer cells (MCF-7) using MTT. The results of cytotoxicity against MCF-7 cells demonstrated a decrease in the cell viability as a function of the concentration, for all the samples tested, being the biopolymeric Schiff bases were more effective antitumor agent than chitosan itself. In lower concentration, the complexes did not show effective decrease on cells viability, especially for zinc complexes. However, at high concentrations a significant increase of cytotoxicity was observed. Therefore, the main contribution expected these work was the synthesis, characterization and biological activity evaluation of these new biopolymeric Schiff bases and complexes, aiming to evaluate the antimicrobial and antitumor activity.

Le développement de méthodes de synthèse asymétriques a largement été exploré au cours des vingt dernières années et en particulier par le biais de réactifs organométalliques. Bien que ces processus mènent à d’excellents résultats en terme d’énantiodiscrimination, l’objectif de cette thèse a été de développer de nouveaux outils de synthèse peu onéreux, respectueux des fonctions sensibles environantes et permettant l’accès aux composés attendus avec de bons rendements et excès énantiomériques. Dans cet optique, des triorganozincates de lithium chiraux ont été étudiés. Des méthodes d’alkylation et d’arylation 1,2 énantiosélectives d’aldéhydes, comportant comme partenaire chiral la (R)-N-(2-iso-butoxybenzyl)-1- phenyléthanamine, ont ainsi été développées et mises en application sur divers aldéhydes. Les alcools secondaires correspondants ont été obtenus avec de bons rendements (jusqu'à 83%) et d’excellents excès énantiomériques (jusqu'à 99%). Ces procédures ont ensuite été appliquées à la synthèse asymétrique de produits naturels et/ou bioactifs tels que la Spiromastilactone A, la (R)-Néobénodine et la (R)-Orphénadrine. Par ailleurs, la synthèse de nouveaux ligands de type amino-alcool a été développée dans le but ultime de désymétriser des substrats de type imines cycliques. / The development of new asymetric methodologies have been widely explored during the last twenty years and in particular through organometallic reagents. Although these processes lead to excellent results in terms of enantiodiscrimination, the goal of this thesis was to develop new tools: cheap, chemoselective and allowing the access to the desired compounds with high yields and enantiomeric excesses. In this context, chiral lithium triorganozincates have been studied. Enantioselective nucleophilic 1,2 alkylation and arylation of aldehydes reactions, including (R)-N-(2-iso-butoxybenzyl)-1-phenylethanamine as the chiral ligand, have been optimized toward various aldehydes. The expected secondary chiral alcohols have been obtained with good yields (up to 83%) and high enantiomeric excesses (up to 99%).These processes have been then applied to the asymmetric synthesis of naturals and/or bioactive compounds as Spiromastilactone A, (R)-Neobenodine and (R)-Orphenadrine. Finally, the access to new amino-alcohols have been developed with the ultimate goal to engage those species as the chiral partner when reacting chiral lithium zincates with imines.