Synthetic efforts toward fumonisin analog were described. These are accomplished via amino acid Schiff base methodology. These efforts can be divided three major phases. First, tandem reductive alkylation with DIBAL/TRIBAL and different types of organo-lithium or Grignard nucleophiles provided threo-amino alcohol with excellent stereoselecitivites (2-27:1). The reductive alkylation utilized most hydrocarbon nucleophiles, e.g. alkyl-, vinyl-, alkenyl-, phenyl-, and dienyl-, and afforded high selectivites unless donor solvents (e.g. THF and Et2O) were used. Second, syntheses of the protected threo-γ-amino-β-hydroxy aldehydes and their stereoselectivities were introduced. The reductive alkylated threo-amino allyl alcohol was transformed via Brown’s hydroboration/oxidation protocol with 9-BBN, followed by TEMPO oxidation to give the resultant aldehydes in reasonable yields. Then, TBDPS and Schiff base protected aldehyde was coupled with phenyl- and decyl Grignard reagents to obtain predominant 3,5-anti-diols (ca. 80:20 anti:syn), characterized by ¹³C NMR analysis of Rychnovsky’s 1,3-acetonide groups. Products can be useful analogues for fumonisin and 5-hydroxy-sphingosine due to their structural similarity. Third stage involved the synthesis of C₁₁-C₂₀ fragment analog of fumonisin. Chiral auxiliaries (e.g. Evans and Myers) were administrated for stereoselective methylation, Sharpless asymmetric dihydroxylation in the presence of (DHQ)2PHAL catalyst was performed to form 1,2- syn-diols, and the manipulation of protection/deprotection and Finklestein reaction furnished C₁₁-C₂₀ fragment analog of fumonisin.

From medicine to aerospace, innovation in multiple fields will not occur without addressing current questions that still exist in polymer behavior and manipulation. This dissertation represents the research carried out over the course of three separate experiments using rheometry as the key technique to explore the behavior of polymer composites. In all three studies, polymer composites were investigated for changes to their known physical properties caused through the addition of a filler or functionalization. Chapter Two examines the possibility of enhancing poly(4-methyl-1-pentene) through the use of soluble carbon nanotubes. In this series of experiments, carbon nanotubes were covalently functionalized using reductive alkylation with a dodecyl group to render them easily soluble in the same organic solvents as low molecular weight poly(4-methyl-1-pentene). The polymer and the functionalized nanotubes were dissolved together in carbon tetrachloride then the solvent is removed leaving the functionalized nanotubes uniformly dispersed in the polymer matrix. The composites were then compression molded and the changes to the physical properties were explored. The functionalized nanotube filler generally acted to plasticize the samples producing transparent but colored polymers. The samples had a lower modulus and glass transition which was the opposite found by Clayton et al. using sonicated pristine carbon nanotubes. Polyurethanes have a growing significance in the biomedical field, and we explore the possibility fine tuning the properties of a polyurethane for such uses in Chapter Three. Here, self healing Polycarbonate polyurethanes (PCU) were synthesized with two different soft segments, Nippollan 964 and T-5652, and characterized with dielectric analysis (DEA), differential scanning calorimetry (DSC) and rheometry. The extra methyl group acted to produce a crystalline-like ordered hard segment that caused the 964 PCU to become Arrhenius in the glass transition region where the 5652 PCU had followed WLF behavior. Results showed the pendent methyl group acted to impart a crystalline-like character to the 964 PCU making it a candidate for applications that would be suited to a stiffer polymer. In Chapter Four we explore the possibility of increasing the wearability and comfort of contact lenses through increased hydration. The hydrogels 2-hydroxyethylmethacrylate (HEMA) and glycidyl methacrylate (GMA) solutions were created in three concentrations; neat, 50/50 and 60/40. Into these samples [Cu2({μ2-CO2}R)4(axial)2] (Cu(II) 4-hydroxybenzoic acid (MHBC) were dissolved 0.05% by weight. The samples were then polymerized via UV polymerization and compression molded. The experiments performed included penetration resistance , water absorption, micro hardness and glass transition. Addition of the MHBC acted to increase the water uptake of the samples but also reduced their ability to withstand mechanical penetration. With further study into crosslinking of the polymers, the MHBC could show promise in increasing hydration for commercial use.

Les hydrotropes sont de petites molécules amphiphiles utilisées dans de nombreux domaines d'applications (détergence, extraction, solubilisation, etc …). Les hydrotropes sont principalement d'origine pétrosourcée et des molécules alternatives d'origine biosourcée ont été synthétisées selon des voies de synthèse éco-compatibles.Deux tétraols, l'érythritol et le pentaérythritol, ont été utilisés comme tête polaire. La partie apolaire est incorporée via une liaison éther car celle-ci est plus résistante en milieux salins. L'alkylation réductrice directe de dérivés carbonylés conduisant à des résultats non satisfaisants, une synthèse en deux étapes d'acétalisation puis d'hydrogénolyse a donc été développée, conduisant aux éthers de tétraols avec de bons rendements. Les propriétés physico-chimiques de ces éthers sont meilleures que celles d'hydrotropes standards, mais non suffisantes pour l'application visée. Ainsi, des éthers de glycérol fonctionnalisés par une fonction carboxylate ont été synthétisés. Une première étape d'alkylation réductrice permet d'accéder aux mono-éthers de glycérol. Une réaction en cascade d'acétalisation puis d'hydrogénolyse à partir de céto-esters permet de greffer la fonction carboxylate. L'alcool libre peut ensuite être méthylé à l'aide du phosphate de triméthyle. Cette méthode de méthylation a ensuite été étendue à de nombreux polyols (érythritol, glycérol, diglycérol, acide tartrique, etc …). Les produits de perméthylation sont obtenus avec de bons rendements, et le catalyseur acide est une résine recyclable / Hydrotropes are small amphiphilic molecules with applications in numerous fields such as extraction, detergency, solubilization, etc … Generally, hydrotropes are petrosourced, thereby biosourced alternatives molecules have been synthesized using eco-compatible synthesis.Two tetraols, erythritol and pentaerythritol, were used as polar head. Ethers bond was retained to link the two parts of the amphiphilic molecule due to its better resistance in saline media. Using carbonyl derivatives, the reductive alkylation didn’t allow to reach the corresponding ethers. A two-step strategy of acetalisation and hydrogenolysis was developed to reach good yields in ethers. The physico-chemical properties of these compounds are better than standard hydrotropes, but they are not sufficient for the targeted application. Thereby, functionalized glycerol ethers with a carboxylic acid have been synthesized. First, reductive alkylation led to glycerol mono-ethers in good yields. Then, acetalisation/hydrogenolysis cascade using ceto-ester enable the addition of carboxylic acid in good yields. Free hydroxyl group can be methylated using trimethylphosphate. This methylation process has been extended to other polyols (erythritol, pentaerythritol, glycerol, diglycerol, etc …). The permethylated products have been obtained in good yields, and the acid catalyst is a recyclable resin

L'objectif de ce travail était d'accéder au squelette des alcaloïdes de type Aspidosperma et Strychnos à partir d'arylcyclohexa-2,5-diènes. Ces derniers sont d'abord synthétisés par réaction de Birch alkylante, puis ont été désymétrisés dans un premier temps par des réactions de Michael. Cette réaction fournit la cétone de Büchi, le noyau tétracyclique des alcaloïdes Aspidosperma en seulement en 6 étapes et un rendement global de 17%. Dans un second temps, la réaction d'amination oxydante catalysée par des métaux (Pd, Cu) a été développée. Cette réaction a permis un accès rapide au squelette pentacyclique d’aza-aspidospermanes et au squelette tétracycliques des alcaloïdes de type Strychnos. En parallèle, nous avons décrit une approche vers le squelette pentacyclique de la mossambine et la strychnine. / The aim of this work was to access the skeleton of the Aspidosperma and the Strychnos alkaloids using arylcyclohexa-2,5-dienes as common synthetic precursors. Initially, these arylcyclohexadienes were synthesized through Birch reductive alkylation reactions. The desymmetrization of these cyclohexadienes was developed via the Michael addition reaction, providing the Büchi ketone, the tetracyclic core of Aspidosperma alkaloids, in only 6 steps and 17% overall yield. On the other hand, we described the oxidative amination reaction catalyzed by metals (Pd, Cu). The palladium oxidative amination reaction allowed a fast access to the pentacyclic framework of aza-aspidospermanes and the tetracyclic framework of the strychnos. In parallel, we have described an approach toward the pentacyclic skeleton of mossambine and strychnine.

L’objectif de cette thèse était d’accéder au squelette de deux grandes familles d’alcaloïdes, les aspidosperma et les morphinanes, avec pour but, l’utilisation de précurseurs communs, les arylcyclohexa-2,5-diènes. Dans un premier temps, ces arylcyclohexa-2,5-diènes, obtenus par réaction de Birch alkylante, ont été désymétrisés par application de la réaction de Michael. Les substrats ainsi obtenus ont été diversement fonctionnalisés jusqu’à obtention du squelette pentacyclique des aspidosperma. Dans un second temps, plusieurs méthodologies utilisant des réactions de type Mannich ont été développées. Ces méthodologies ont permis d’atteindre une base tricyclique de la famille des morphinanes. Plusieurs transformations ont ensuite été examinées afin d’accéder au squelette tétracyclique avancé de cette famille d’alcaloïdes. / The objective of this work was to access the skeleton of two families of alkaloids, the aspidosperma and the morphinan, using arylcyclohexa-2,5-dienes as common synthetic precursors. In one hand, these arylcyclohexadienes, synthesized by reductive Birch alkylation, were desymmetrized via the Michael reaction. The resulting compounds were then functionalized to give the pentacyclic skeleton of aspidosperma alkaloids. On the other hand, several methodologies were developed using Mannich type reactions. These methodologies allowed an access to the tricyclic framework of the morphinan family. Several transformations were then examined to attain the tetracyclic skeleton of this family of alkaloids.

Ces dernières années, la notion de Développement Durable a bouleversé la recherche académique etindustrielle dans le domaine de la chimie. L’utilisation de matières premières issues des ressources renouvelables en constitue l’un des aspects les plus marquants. De même, le développement de procédés originaux, qui s’appuient sur des systèmes catalytiques recyclables, des transformations chimiques innovantes et de nouveaux solvants plus respectueux de l’environnement font l’objet d’un intérêt croissant, en raison des gains environnementaux et économiques. Les travaux de recherche décrits dans cette thèse s’inscrivent dans ce contexte et présentent la mise au point de nouvelles voies d’accès aux éthers de glycérol, des molécules à haute valeur ajoutée. Plusieurs procédés originaux ont été développés en utilisant le glycérol comme substrat biosourcé issu de l’industrie oléo-chimique. Ainsi, l’alkylation réductrice d’acides carboxyliques avec le glycérol en présence de palladium sur charbon et d’une résine acide a permis de préparer une variété de 1-Oalkyléthersde glycérol. Une procédure alternative a été développée à partir des huiles végétales et des esters méthyliques, par transestérification puis réduction de l’ester intermédiaire sous hydrogénation catalytique. Ensuite, un procédé d’alkylation déshydrogénante de dérivés de la cyclohexanone avec le glycérol a donné un nouvel accès aux 1-O-aryléthers de glycérol et a été étendu aux éthers et aux amines aromatiques. Enfin, de nouveaux solvants aprotiques dérivés du glycérol ont été synthétisés par une catalyse de transfert de phase. En particulier, la toxicité du 1,2,3-triméthoxypropane ainsi que son utilisation dans des transformations chimiques comme nouveau solvant ont été évaluées. / In recent years, sustainable development brought unprecedented changes in industrial and academic researches. The use of raw materials from renewable resources is one of the most outstanding aspects of these changes. The development of original processes, with recyclable catalytic systems, new chemical transformations as well as new solvents with a lower environmental impact are of growing interest, because of environmental and economical profits. The research work described in this thesisis focused on the development of new accesses to glyceryl ethers as high value added coumpounds.Thus, several processes were developed by using glycerol as accessible and bio-based starting material from the oleochemical industry. First, we found a benign and eco-friendly process for the synthesis of1-O-alkyl glyceryl ethers by catalytic reductive alkylation of carboxylic acids with a recyclable catalytic system associating palladium on carbon and an acid ion exchange resin. A second two steps procedure was also developed when starting from a vegetable oil or a methyl ester, which was transesterified to the corresponding monoglyceride followed by its reduction by catalytic hydrogenation. We report also a straight forward and palladium catalyzed dehydrogenative alkylation of cyclohexanone derivatives with alcohols, including glycerol, and amines in order to prepare avariety or aryl ethers and aryl amines. Finally, we prepared new aprotic and glycerol-based solvents bya solvent-free phase-transfer catalysis. In particular, the toxicity of 1,2,3-trimethoxypropane and its utilization as alternative solvent in chemical transformations was evaluated.

Made available in DSpace on 2014-12-17T15:41:41Z (GMT). No. of bitstreams: 1 KeilaSA.pdf: 2159921 bytes, checksum: eaf4fb1bec7305fa007222908f6259ac (MD5) Previous issue date: 2008-02-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Chitosan derivatives were prepared by reductive alkylation using glutaraldehyde and 3-amino-1-propanol. The reducing agent used was the sodium borohydride. Tests of solubility, stability and viscosity were performed in order to evaluate these parameters effects in the reaction conditions (molar ratio of the reactants and presence of nitrogen in the reaction system). The molecular structure of commercial chitosan was determined by infrared (IR) and hydrogen nuclear magnetic resonance spectroscopy (1H NMR). The intrinsic viscosity and average molecular weight of the chitosan were determined by viscosimetry in 0.3 M acetic acid aqueous solution 0.2 M sodium acetate at 25 ?C. The derivatives of chitosan soluble in aqueous acidic medium were characterized by 1H NMR. The rheological behavior of the chitosan and of the derivative of chitosan (sample QV), which presented the largest viscosity, were studied as a function of polymer concentration, temperature and ionic strength of the medium. The results of characterization of the commercial chitosan (the degree of deacetylation obtained equal 78.45 %) used in this work confirmed a sample of low molar weight (Mv = 3.57 x 104 g/mol) and low viscosity (intrinsic viscosity = 213.56 mL/g). The chemical modification of the chitosan resulted in derivatives with thickening action. The spectra of 1H NMR of the soluble derivatives in acid aqueous medium suggested the presence of hydrophobic groups grafted into chitosan in function of the chemical modification. The solubility of the derivatives of chitosan in 0.25 M acetic acid aqueous solution decreased with increase of the molar ratio of the glutaraldehyde and 3-amino-1-propanol in relation to the chitosan. The presence of nitrogen and larger amount of reducing agent in reaction system contributed to the increase of the solubility, the stability and the viscosity of the systems. The viscosity of the polymeric suspensions in function of the shear rate increased significantly with polymer concentration, suggesting the formation of strong intermolecular associations. The chitosan presented pseudoplastic behavior with the increase in polymer concentration at a low shear rate. The derivative QV presented pseudoplastic behavior at all concentrations used and in a large range of shear rate. The viscosity of chitosan in solution decreased with an increase of the temperature and with the presence of salt. However, there was an increase of the viscosity of the chitosan solution at higher temperature (65 ?C) and ionic strength of the medium which were promoted by hydrophobic associating of the acetamide groups. The solutions of the chitosan derivatives (sample QV) were significantly more viscous than chitosan solution and showed higher thermal stability in the presence of salt as a function of the hydrophobic groups grafted into chitosan backbone / Derivados de quitosana foram preparados atrav?s de alquila??o redutiva usando glutaralde?do e 3-amino-1-propanol. O agente redutor utilizado foi o boro hidreto de s?dio. Os efeitos das vari?veis reacionais (propor??es molares dos reagentes e nitrog?nio no meio reacional) nas caracter?sticas dos pol?meros em fun??o das mudan?as estruturais foram avaliados atrav?s de testes de solubilidade, estabilidade e viscosidade. A estrutura molecular da quitosana comercial foi determinada por espectroscopia de infravermelho (IV) e de resson?ncia magn?tica nuclear de hidrog?nio (RMN 1H). A viscosidade intr?nseca e a massa molar m?dia da quitosana foram determinadas por viscosimetria, em ?cido ac?tico 0,3 M acetato de s?dio 0,2 M, a 25 ?C. Os derivados de quitosana sol?veis em meio aquoso ?cido foram caracterizados por RMN 1H. O comportamento reol?gico da quitosana e do seu derivado (amostra QV), que apresentou maior viscosidade, foram estudados em fun??o da concentra??o de pol?mero, da temperatura e da for?a i?nica do meio. Os resultados da caracteriza??o da quitosana comercial utilizada neste trabalho demonstraram uma amostra de baixa massa molar (Mv = 3,57 x 104 g/mol) e de baixa viscosidade (viscosidade intr?nseca = 213,56 mL/g). O grau m?dio de desacetila??o foi 78,45 %. A modifica??o qu?mica da quitosana resultou em derivados com caracter?sticas viscosificantes. Os espectros de RMN 1H dos derivados sol?veis em meio aquoso ?cido mostraram a inser??o de grupos hidrof?bicos na estrutura da quitosana em fun??o da modifica??o qu?mica realizada. A solubilidade dos derivados de quitosana em solu??o aquosa de ?cido ac?tico 0,25 M diminuiu com o aumento da propor??o molar do glutaralde?do e 3-amino-1-propanol em rela??o ? quitosana. A presen?a de nitrog?nio e maior quantidade de agente redutor no meio reacional contribu?ram para o aumento da solubilidade, estabilidade e viscosidade dos sistemas polim?ricos. A viscosidade das dispers?es polim?ricas em fun??o da taxa de cisalhamento aumentou significativamente com a concentra??o de pol?mero, sugerindo a forma??o de fortes associa??es intermoleculares. A quitosana apresentou comportamento pseudopl?stico com o aumento da concentra??o de pol?mero em solu??o e a baixas taxas de cisalhamento, enquanto que o seu derivado, QV, apresentou comportamento pseudopl?stico em todas as concentra??es utilizadas e em uma larga faixa de taxa de cisalhamento. A viscosidade da solu??o de quitosana diminuiu com o aumento da temperatura e com a presen?a de sal. No entanto, houve um aumento da viscosidade da solu??o de quitosana ? temperatura mais alta (65 ?C) e em maior for?a i?nica, promovido por associa??es hidrof?bicas dos grupos acetamido. As solu??es do derivado QV foram significativamente mais viscosas do que as solu??es de quitosana e obtiveram maior estabilidade t?rmica em solu??o na presen?a de sal em fun??o dos grupos hidrof?bicos inseridos na estrutura da quitosana

Made available in DSpace on 2014-12-17T15:42:30Z (GMT). No. of bitstreams: 1 KeilaSA_TESE.pdf: 6694216 bytes, checksum: df1754b48618e11f2ae95e003ae20c2c (MD5) Previous issue date: 2013-12-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Chitosan is a biopolymer derived from the shells of crustaceans, biodegradable, inexpensive and renewable with important physical and chemical properties. Moreover, the different modifications possible in its chemical structure generate new properties, making it an attractive polysaccharide owing to its range of potential applications. Polymers have been used in oil production operations. However, growing concern over environmental constraints has prompted oil industry to search for environmentally sustainable materials. As such, this study sought to obtain chitosan derivatives grafted with hydrophilic (poly(ethylene glycol), mPEG) and/or hydrophobic groups (n-dodecyl) via a simple (one-pot) method and evaluate their physicochemical properties as a function of varying pH using rheology, small-angle Xray scattering (SAXS), dynamic light scattering (DLS) and zeta potential. The chitosan derivatives were prepared using reductive alkylation under mild reaction conditions and the chemical structure of the polymers was characterized by nuclear magnetic resonance (1H NMR) and CHN elemental analysis. Considering a constant mPEG/Chitosan molar ratio on modification of chitosan, the solubility of the polymer across a wide pH range (acidic, neutral and basic) could only be improved when some of the amino groups were submitted to reacetylation using the one-pot method. Under these conditions, solubility is maintained even with the simultaneous insertion of n-dodecyl. On the other hand, the solubility of derivatives obtained only through mPEG incorporation using the traditional methodology, or with the ndodecyl group, was similar to that of its precursor. The hydrophilic group promoted decreased viscosity of the polymer solutions at 10 g/L in acid medium. However, at basic pH, both viscosity and thermal stability increased, as well as exhibited a pronounced pseudoplastic behavior, suggesting strong intermolecular associations in the alkaline medium. The SAXS results showed a polyelectrolyte behavior with the decrease in pH for the polymer systems. DLS analyses revealed that although the dilute polymer solutions at 1 g/L and pH 3 exhibited a high density of protonated amino groups along the polymer chain, the high degree of charge contributed significantly to aggregation, promoting increased particle size with the decrease in pH. Furthermore, the hydrophobic group also contributed to increasing the size of aggregates in solution at pH 3, whereas the hydrophilic group helped reduce their size across the entire pH range. Nevertheless, the nature of aggregation was dependent on the pH of the medium. Zeta potential results indicated that its values do not depend solely on the surface charge of the particle, but are also dependent on the net charge of the medium. In this study, water soluble associative polymers exhibit properties that can be of great interest in the petroleum industry / A quitosana ? um biopol?mero derivado de carapa?as de crust?ceos, de baixo custo, biodegrad?vel, renov?vel, que apresenta propriedades f?sico-qu?micas importantes e, ainda, proporciona diferentes possibilidades de modifica??es em sua estrutura qu?mica, gerando novas propriedades, o que torna esse polissacar?deo muito atraente do ponto de vista de aplica??o. Os pol?meros s?o utilizados em v?rias opera??es na produ??o do petr?leo. Entretanto, a crescente preocupa??o com as restri??es ambientais t?m promovido a busca por materiais ambientalmente sustent?veis pela ind?stria do petr?leo. Dessa forma, esse estudo prop?s a obten??o de quitosana graftizada com grupos hidrof?lico (poli(etileno glicol), mPEG) e/ou hidrof?bico (n-dodecila) por uma metodologia mais simples (one-pot) e a avalia??o de suas propriedades f?sico-qu?micas em fun??o da varia??o de pH, atrav?s das an?lises de reologia, espalhamento de raios-X a baixos ?ngulos (SAXS), espalhamento de luz din?mico (DLS) e potencial zeta. Os derivados de quitosana foram preparados utilizando a rea??o de alquila??o redutiva em condi??es reacionais brandas e a estrutura qu?mica dos pol?meros foi caracterizada por resson?ncia magn?tica nuclear de hidrog?nio (RMN 1H) e an?lise elementar CHN. Considerando constante a raz?o molar mPEG/Quitosana na modifica??o qu?mica da quitosana em diferentes metodologias, foi poss?vel melhorar a solubilidade da quitosana em uma ampla faixa de pH (?cido, neutro e b?sico) usando a metodologia one-pot, em que uma parte dos grupos amino foi reacetilada. Nesta condi??o, at? mesmo com a inser??o simult?nea do n-dodecila, a solubilidade se manteve. Por outro lado, a solubilidade dos derivados obtidos apenas com a incorpora??o de mPEG atrav?s de metodologia tradicional, ou com o grupo ndodecila, foi similar ao seu precursor. O grupo hidrof?lico promoveu a diminui??o da viscosidade das solu??es polim?ricas a 10 g/L em meio ?cido. Entretanto, em pH b?sico, esse grupo contribuiu para o aumento da viscosidade e da estabilidade t?rmica das solu??es, assim como, favoreceu um comportamento pseudopl?stico mais acentuado, sugerindo fortes associa??es intermoleculares no meio alcalino. Os resultados de SAXS apresentaram um comportamento de polieletr?lito com a diminui??o do pH para os sistemas polim?ricos. As an?lises de DLS revelaram que as solu??es dilu?das dos pol?meros a 1 g/L em pH 3, embora apresentem uma alta densidade de grupos amino protonados ao longo da cadeia polim?rica, o alto grau de cargas contribuiu significativamente para a agrega??o, promovendo o aumento do tamanho das part?culas com a diminui??o do pH. Al?m disso, o grupo hidrof?bico tamb?m contribuiu para aumentar o tamanho dos agregados em solu??o no pH 3 e o grupo hidrof?lico favoreceu para reduzi-los em toda faixa de pH. Entretanto, a natureza de agrega??o foi dependente do pH do meio. Os resultados do potencial zeta indicaram que seus valores n?o dependem apenas da carga da superf?cie da part?cula, mas ? resultante da carga l?quida do meio. Os sistemas polim?ricos associativos em solu??o aquosa obtidos neste estudo apresentam propriedades que podem ser atraentes em v?rias aplica??es na ind?stria do petr?leo