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O objetivo do presente trabalho foi determinar as estruturas cristalinas e moleculares de cocristais de 2,4,6-trinitrofenol, ou ácido pícrico, com diversas bases orgânicas, bem como estudar as interações intermoleculares existentes nesses cocristais para tentar estabelecer um padrão de comportamento na formação de ligações de hidrogênio e de preferências estruturais, com a finalidade de contribuir para o entendimento do empacotamento cristalino. Foram sintetizados os seguintes compostos: 1:1 picrato/8-hidroxiquinolina, 1:1 picrato/isonicotinamida, 1:1 picrato/2-azaciclononanona, 1:2 picrato/2-azaciclotridecanona, 1:1 picrato/morfolina, 1:1 picrato/1,3 dimetiluréia, 1:1 picrato/4-metil-morfolina-N-óxido, 1:2 picrato/3-picolina-N-óxido, 1:2 picrato/glicina e 1:1 picrato/prolina. Esses compostos foram caracterizados por análise elementar CHN, para a confirmação da estequiometria, pelos pontos de fusão, e para o cocristal de picrato/prolina foram registrados espectros de emissão na região entre 430 e 650 nm e o espectro de excitação na região entre 360 e 500 nm, onde foi observado que o composto é transparente na região acima de 500 nm, sendo portanto favorável aos experimentos de duplicação de radiação laser Nd/YAG (λ = 1.064 nm), uma vez que não absorve na região da radiação duplicada (λ =532 nm). A coleta de dados, a obtenção das intensidades dos feixes difratados pelos monocristais, para a determinação das estruturas cristalinas foi realizada em um difratômetro Enraf-Nonius CAD4 Mach 3. As intensidades observadas medidas foram convertidas em fatores de estrutura observados através da correção pelos fatores de Lp e de absorção. As estruturas foram determinadas utilizando os chamados Métodos Diretos e refinadas por cálculos sucessivos de Fourier-Diferença e mínimos quadrados. Ao final da determinação das estruturas dos dez cocristais pôde-se analisar um total de 50 ligações de hidrogênio do tipo O-H...O, N-H...O e C-H...O. Essas ligações de hidrogênio foram analisadas geometricamente em relação às distâncias e ângulos de ligações, e também foram nomeadas e classificadas pelo método Graph-set. Através destas análises pode-se chegar a uma comparação entre as estruturas e a padrões comuns em relação às ligações intermoleculares existentes. Observa-se que as ligações de hidrogênio do tipo O-H...O mais fortes são aquelas formadas entre o grupo doador e os oxigênios fenólicos receptores do picrato. As distâncias d(H...O) das ligações de hidrogênio correspondentes a O-H...O (oxigênio fenólico) estão concentrados na região entre 1,51 e 1,82 Å, e os ângulos <OHO concentram-se na região entre 161 e 171º. As distâncias d(O...O) estão compreendidas entre 2,48 e 3,1 Å. Para as ligações O-H...O (oxigênio do grupo nitro) as distâncias d(H...O) estão entre 2,41 e 2,54 Å e ângulos <OHO na região entre 100 e 121º. Também é observado que as distâncias d(O...O) estão compreendidas entre 2,78 e 3,04 Å, mas predominantemente estão na faixa entre 2,4 e 2,55 Å. Para as interações do tipo N-H...O, observa-se que as distâncias d(H...O) estão em um intervalo entre 1,85 e 2,52 Å; e em relação aos ângulos <NHO, estão distribuídos no intervalo entre 121 e 171º. Um intervalo bastante largo é observado em relação as distâncias d(N...O), que estão compreendidas entre 2,6 e 3,2Å. Para as interações do tipo C-H...O, observa-se que as distâncias d(H...O) tem uma leve tendência crescente em função do aumento do ângulo <CHO, e encontram-se no intervalo entre 2,96 e 3,61 Å. / The objective of the present work is to determine the crystalline and molecular structures of 2,4,6 trinitrophenol (picric acid ) cocrystals, with several organic bases, as well as to study the intermoleculares interactions existent in those cocristals in order to establish a pattern of behaviour in the formation of hydrogen bonds and structural preferences, with the purpose of contributing for the understanding of crystalline packing. Was synthesized the following compounds: 1:1 picrate/8-hidroxiquinoline, 1:1 picrate/isonicotinamide, 1:1 picrate/2-azacyclononanone, 1:1 picrate/morfoline, 1:1 picrate/1,3 dimethylurea, 1:1 picrate/ 4-methyl-morfoline-N-oxide, 1:2 picrate/3-picoline-N-oxide, 1:2 picrate/glycine, 1:1 picrate/proline. Those compositions were characterized by elemental analysis (CHN) for the stoichiometry confirmation, melting points and, for the picrate/proline cocrystal, the emission and excitation spectra were recorded. It was observed that this compound is transparent above 500 nm, being therefore suitable to experiments of Nd/YAG laser radiation duplication (λ = 1.064 nm), since it does not absorb at the wavelength of the duplicated radiation (λ = 532 nm). Data collection for crystalline structure determination\'s was accomplished in an Enraf-Nonius CAD4 Mach 3 diffractometer. The observed intensities were transformed into structure factors observed through Lp and absorption corrections. The structures were determined using the direct method and refined by successive Fourier-difference calculations and least-square analysis. At the end of this determination some hydrogen bonds, O-H ...O, N-H ...O and C-H ...O could be analyzed. Those hydrogen bonds were geometrically analysed with relation to bond distances and angle, and they were also nominated and classified by the Graph-set method. Through these analyses it was possible a comparison among the structures and to common patterns in relation to intermolecular bonds. It was observed that the stronger hydrogen bonds are those formed between the donor group and the phenolic picrate oxygen. The O-H ...O (phenolic oxygen) distances d(H ...O) are concentrated in range 1.51 and 1.82 Å, and angles <OHO are concentrated between 161 and 171Å. The distances d(O...O) are between 2.48 and 3.1 Å. The distances of hydrogen bonds O-H ...O (nitro group oxygen), d(H ...0), are in the range 2.41 and 2.54 Å and angles <OHO between 100 and 121º. It is also observed that distances d(O ...O) lie between 2.78 and 3.04 Å. but predominantly they are in the interval between 2.4 and 2.55 Å. For interactions of the type N-H ...O. it is observed that distances d(H ...O) are between 1.85 and 2.52 Å, and angles <NHO, are between 121 and 171º. A quite wide area is observed with relation to the distance d(N ...O), that lie between 2.6 and 3.2 Å. For interactions of the type C-H ...O. it is observed that distances d(H ...O) increase in function of the angle <CHO; they lie between 2.96 and 3.61 Å.

Dans un premier temps, la bis- et tris-fonctionnalisation du C60 a été effectuée par une approche macrocyclique. Différents bis- et tris-adduits du C60 ont été obtenus avec de bonnes régioselectivités. Dans un deuxième temps, la tris-fonctionnalisation du C60 a été effectuée par une approche « tête directrice ». Par cette approche, un accès rapide, simple, régio- et stéréo-sélectif à des tris-adduits e,e,e approprié à la formation d’hexa-adduits d’ordre d’addition octaédrique a été obtenu. La synthèse et la séparation de tris-adduits e,e,e optiquement purs ont également été réalisées. Les dérivés polyols obtenus par déprotection des groupes silylés ouvrent de nouvelles perspectives pour la post-fonctionnalisation de multi-adduits de C60. A partir de nos méthodologies de synthèse de bis- et tris-adduits de C60, des synthons d’hexa-adduits mixtes de C60 ont été préparés. La post-fonctionnalisation de ces synthons a été effectuée par réaction de cycloaddition1,3-dipolaire de type Huisgen mais aussi par réaction d’estérification, afin d’obtenir des hexa-adduitsde C60 multifonctionnels. La méthodologie de synthèse d’hexa-adduits de C60 multifonctionnels aété mise à profit pour l’élaboration d’édifices hyperfonctionnels comportant plusieurs hexa-adduits de C60 autour d’un hexa-adduit de C60 central. La post-fonctionnalisation des synthons hexa-adduits mixtes par chimie « click » donne accès à la préparation contrôlée de nouveaux nanomatériaux globulaires multifonctionnels. / In a first instance, the bis- and tris-functionalization of C60 was performed by a macrocyclic approach. Different bis- and tris-adducts of C60 were obtained with good regioselectivity. In a second instance, the tris-functionalization of C60 was performed by a “tether-directed” approach. By this approach, a fast, simple, regio- and stereoselective access to C60 e,e,e tris-adduct suitable for the formation of C60 hexa-adducts with an octahedral addition pattern was obtained. The synthesis and the separation of optically pure e,e,e tris-adducts was also realized. The polyol derivatives obtained by deprotection of the silyl groups open new perspectives for the post-functionalization of C60 multiadducts. Using our synthesis methodologies of bis- and tris-adducts of C60, mixed hexa-adducts building blocks were prepared. The post-functionalization of these building blocks was carried out by copper catalyzed azide-alkyne 1,3-dipolar cycloadditions but also by esterification reactions to obtain multifunctional C60 hexa-adducts. The methodology for the synthesis of multifunctional C60 hexa-adducts was used for the elaboration of fullerodendrimers containing several C60 hexa-adducts around a central C60 hexa-adduct. The post-functionalization of the mixed hexa-adducts building blocks by “click” chemistry gave access to the controlled preparation of new globular and multifunctional nanomaterials.

Cellulose in particular and wood in general are valuable biomaterials for humanity, and cellulose is now also in the spotlight as a starting material for the production of biofuel. Understanding the processes of wood formation and cellulose biosynthesis could therefore be rewarding, and genomics and proteomics approaches have been initiated to learn more about wood biology. For example, the genome of the tree Populus trichocarpa has been completed during 2006. A single-gene approach then has to follow, to elucidate specific patterns and enzymatic details. This thesis depicts how a gene encoding a membrane-anchored cellulase was isolated from Populus tremula x tremuloides Mich, how the corresponding protein was expressed in heterologous hosts, purified and characterized by substrate analysis using different techniques. The in vivo function and modularity of the membrane-anchored cellulase was also addressed using overexpression and complementation analysis in Arabidopsis thaliana. Among 9 genes found in the Populus EST database, encoding enzymes from glycosyl hydrolase family 9, two were expressed in the cambial tissue, and the membrane-anchored cellulase, PttCel9A1, was the most abundant transcript. PttCel9A1 was expressed in Pichia pastoris, and purified by affinity chromatography and ion exchange chromatography. The low yield of recombinant protein from shake flask experiments was improved by scaling up in the fermentor. PttCel9A1 was however highly heterogenous, both mannosylated and phosphorylated, which made the protein unsuitable for crystallization experiments and 3D X-ray structure determination. Instead, a homology model using a well-characterized, homologous bacterial enzyme was built. From the homology model, interesting point mutations in the active site cleft that would highlight the functional differences of the two proteins could be identified. The real-time cleavage patterns of cello-oligosaccharides by mutant bacterial enzymes, the wildtype bacterial enzyme and PttCel9A1 were studied by 1H NMR spectroscopy, and compared with results from HPAEC-PAD analysis. The inverting stereochemistry for the hydrolysis reaction of the membrane-anchored poplar cellulase was also determined by 1H NMR spectroscopy, and it was concluded that transglycosylation in vivo is not a possible scenario. The preferred in vitro polymeric substrates for PttCel9A1 were shown to be long, low-substituted cellulose derivatives, and the endo-1,4--glucanase activity was not extended to branched or mixed linkage substrates to detectable levels. This result indicates an in vivo function in the hydrolysis of “amorphous” regions of cellulose, either during polymerization or crystallization of cellulose. In addition, overexpressing PttCel9A1 in A. thaliana, demonstrated a correlation with decreased crystallinity of cellulose. The significance of the different putative modules of PttCel9A1 was investigated by the construction of hybrid proteins, that were introduced into a knock-out mutant of A. thaliana, and the potential complementation of the phenotype was examined. A type B plant cellulase catalytic domain could not substitute for a type A plant cellulase catalytic domain, although localization and interaction motifs were added to the N- and C-terminus. / QC 20100802

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The purpose of this study was to conduct a phytochemical study of the crude extract of the root bark of the species Discaria americana Gilles and Hooker. The origin of this knowledge has been proposed the use of this plant in popular medicine for the treatment of various diseases such as fever, skin diseases, stomach disorders, diabetes and as a tonic in the form of teas and infusions. Through this study was isolated six compounds among which four are cyclopeptide alkaloids, one cyclopeptide alkaloid neutral and one triterpenoid. Cyclopeptide alkaloids isolated are known as Discarine B (23) C Discarine (44) Frangufoline (26) and Frangulanine (27). The cyclopeptide alkaloid neutral is known as Discarene C (63) and triterpenoid is known as Betulinic Acid (69). In this study it was possible to determine the absolute configuration of the compound Discarine C (44) by X-ray diffraction and derivatisation of the amino acids present in the molecule, which were subjected to enantiosselective gas chromatography. Still in phytochemical analysis, we determined the significant activity of some of the isolated compounds. The alkaloid ciclopeptídico Discarine B (23), Discarine C (44), Frangulanine (27) and cyclopeptide alkaloid neutral Discarene C (63) proved strong bacteriostatic against the strain Salmonella typhimurium being the Discarine C (44) showed strong potential bactericidal front of this strain. Discarine B (23) showed significant potential bacteriostatic and bactericidal against the Enterococcus spp and appreciable potential bacteriostatic front Escherechia coli. It was possible to establish a relationship between their structure and configuration and its antimicrobial activity. / A proposta deste trabalho foi a de realizar um estudo fitoquímico do extrato bruto das cascas das raízes da espécie Discaria americana Gilles and Hooker. A origem dessa proposta vem do conhecimento do uso dessa planta na medicina popular para o tratamento de várias enfermidades tais como febre, doenças de pele, afecções no estômago, diabetes e como tônico, na forma de chás e infusões. Por meio deste estudo foi possível isolar seis compostos, dentre os quais quatro são alcalóides ciclopeptídicos, um alcalóide ciclopeptídico neutro e um triterpenóide. Os alcalóides ciclopeptídicos isolados são conhecidos como Discarina B (23), Discarina C (44), Frangufolina (26) e Frangulanina (27). O alcalóide ciclopeptídico neutro é conhecido como Discareno C (63) e o triterpenóide é conhecido como Ácido Betulínico (69). Neste estudo foi possível determinar a configuração absoluta do composto Discarina C (44) através de Difração de Raio-X e derivatização dos aminoácidos presentes na molécula, os quais foram submetidos à cromatografia gasosa enantiosseletiva. Ainda na análise fitoquímica foi possível constatar a atividade significativa de alguns dos compostos isolados. Os alcalóides ciclopeptídicos Discarina B (23), Discarina C (44), Frangulanina (27) e o alcalóide ciclopeptídico neutro Discareno C (63) se mostraram fortes bacteriostáticos frente à cepa Salmonella typhimurium, sendo que a Discarina C (44) apresentou forte potencial bactericida frente a essa cepa. Discarina B (23) apresentou significativo potencial bacteriostático e bactericida frente à Enterococcus spp e apreciável potencial bacteriostático frente à Escherechia coli. Foi possível estabelecer uma relação entre suas estruturas e configurações e seu potencial antimicrobiano.

A l’exception du chapitre bibliographique, cette thèse a été rédigée sous forme d’articles avec des résumés et des discussions tout en comparant les résultats obtenus à d’autres résultats de la littérature dans la même thématique de recherche. Ce travail s’organise en trois axes de recherche : la synthèse organique et la chimie des polymères, la physicochimie de la surface et l’étude de la réponse biologique et de la dégradation des polymères. La problématique de ce sujet de thèse s’articule autour de la resténose intra-stent qui représente la complication majeure de l’angioplastie par pose de stent dans les artères sténosées. Les stents actifs restent la solution actuellement utilisée pour le traitement de la resténose. Ce sont des stents métalliques recouverts d’un polymère qui comporte une substance bioactive généralement un antiprolifératif. Le rôle du polymère est de créer une barrière protectrice entre le métal et la paroi artérielle. Cette barrière doit améliorer la rugosité et la composition chimique du stent métallique, réparer l’endothélium par la prolifération des cellules endothéliales et inhiber la prolifération et la migration des cellules musculaires lisses qui sont responsables d’une façon directe de la reformation de la plaque d’athérome. Les propriétés de surface du polymère lui confèrent un fort pouvoir d’adhérence au métal et de biocompatibilité vis-à-vis de la paroi artérielle. Les interactions créées entre le revêtement polymère et les cellules vasculaires sont modulées par les propriétés physicochimiques de la surface. C’est dans cette optique que mon sujet de thèse est organisé en deux thématiques. / With the exception of bibliographic chapter, this thesis was written in the format of collection of articles with abstracts and discussions while comparing the results with other’s in the literature in the same research theme. This work is organized in three tasks: organic synthesis and stereochemistry of polymers, surface physicochemical properties and biological response and degradation study of polymers. The issue of this thesis is based on in-stent restenosis which represents the major complications of angioplasty with stent placement. Drug-eluting stents are currently the solution used for the restenosis treatment. These are metal stents coated with a polymer having a bioactive substance which is generally an antiproliferative agent. The polymer role is to create a protective barrier between the metal and the arterial wall. This barrier must improve the roughness and the chemical composition of the metallic stent, repair the endothelium by the proliferation of endothelial cells and inhibit the proliferation and the migration of smooth muscle cells which are responsible to the reformation of atheroma plaque. The surface properties confer to polymer a strong adhesiveness to the metal and biocompatibility vis-a-vis of the arterial wall. Interaction created between the polymer coating and vascular cells are modulated by the physicochemical properties of the surface. It is in this context that my thesis is organized into two themes.The first aim of my thesis is to develop a series of amorphous polymers and study their physicochemical (wettability, roughness ...) and biological properties (adhesion, cell behavior and proliferation) and then correlate these properties to choose the promising coating coronary stent. A degradation study was also conducted on elaborate systems. The second is dedicated to chemical synthesis and stereochemistry of polymers. Indeed, new optically active monomers and the corresponding stereopolyesters were synthesized and characterized in order to compare their physicochemical properties with those of amorphous polyesters studied as a coating of the stent and enhance the biomaterials field.

O objetivo do presente trabalho foi determinar as estruturas cristalinas e moleculares de cocristais de 2,4,6-trinitrofenol, ou ácido pícrico, com diversas bases orgânicas, bem como estudar as interações intermoleculares existentes nesses cocristais para tentar estabelecer um padrão de comportamento na formação de ligações de hidrogênio e de preferências estruturais, com a finalidade de contribuir para o entendimento do empacotamento cristalino. Foram sintetizados os seguintes compostos: 1:1 picrato/8-hidroxiquinolina, 1:1 picrato/isonicotinamida, 1:1 picrato/2-azaciclononanona, 1:2 picrato/2-azaciclotridecanona, 1:1 picrato/morfolina, 1:1 picrato/1,3 dimetiluréia, 1:1 picrato/4-metil-morfolina-N-óxido, 1:2 picrato/3-picolina-N-óxido, 1:2 picrato/glicina e 1:1 picrato/prolina. Esses compostos foram caracterizados por análise elementar CHN, para a confirmação da estequiometria, pelos pontos de fusão, e para o cocristal de picrato/prolina foram registrados espectros de emissão na região entre 430 e 650 nm e o espectro de excitação na região entre 360 e 500 nm, onde foi observado que o composto é transparente na região acima de 500 nm, sendo portanto favorável aos experimentos de duplicação de radiação laser Nd/YAG (λ = 1.064 nm), uma vez que não absorve na região da radiação duplicada (λ =532 nm). A coleta de dados, a obtenção das intensidades dos feixes difratados pelos monocristais, para a determinação das estruturas cristalinas foi realizada em um difratômetro Enraf-Nonius CAD4 Mach 3. As intensidades observadas medidas foram convertidas em fatores de estrutura observados através da correção pelos fatores de Lp e de absorção. As estruturas foram determinadas utilizando os chamados Métodos Diretos e refinadas por cálculos sucessivos de Fourier-Diferença e mínimos quadrados. Ao final da determinação das estruturas dos dez cocristais pôde-se analisar um total de 50 ligações de hidrogênio do tipo O-H...O, N-H...O e C-H...O. Essas ligações de hidrogênio foram analisadas geometricamente em relação às distâncias e ângulos de ligações, e também foram nomeadas e classificadas pelo método Graph-set. Através destas análises pode-se chegar a uma comparação entre as estruturas e a padrões comuns em relação às ligações intermoleculares existentes. Observa-se que as ligações de hidrogênio do tipo O-H...O mais fortes são aquelas formadas entre o grupo doador e os oxigênios fenólicos receptores do picrato. As distâncias d(H...O) das ligações de hidrogênio correspondentes a O-H...O (oxigênio fenólico) estão concentrados na região entre 1,51 e 1,82 Å, e os ângulos <OHO concentram-se na região entre 161 e 171º. As distâncias d(O...O) estão compreendidas entre 2,48 e 3,1 Å. Para as ligações O-H...O (oxigênio do grupo nitro) as distâncias d(H...O) estão entre 2,41 e 2,54 Å e ângulos <OHO na região entre 100 e 121º. Também é observado que as distâncias d(O...O) estão compreendidas entre 2,78 e 3,04 Å, mas predominantemente estão na faixa entre 2,4 e 2,55 Å. Para as interações do tipo N-H...O, observa-se que as distâncias d(H...O) estão em um intervalo entre 1,85 e 2,52 Å; e em relação aos ângulos <NHO, estão distribuídos no intervalo entre 121 e 171º. Um intervalo bastante largo é observado em relação as distâncias d(N...O), que estão compreendidas entre 2,6 e 3,2Å. Para as interações do tipo C-H...O, observa-se que as distâncias d(H...O) tem uma leve tendência crescente em função do aumento do ângulo <CHO, e encontram-se no intervalo entre 2,96 e 3,61 Å. / The objective of the present work is to determine the crystalline and molecular structures of 2,4,6 trinitrophenol (picric acid ) cocrystals, with several organic bases, as well as to study the intermoleculares interactions existent in those cocristals in order to establish a pattern of behaviour in the formation of hydrogen bonds and structural preferences, with the purpose of contributing for the understanding of crystalline packing. Was synthesized the following compounds: 1:1 picrate/8-hidroxiquinoline, 1:1 picrate/isonicotinamide, 1:1 picrate/2-azacyclononanone, 1:1 picrate/morfoline, 1:1 picrate/1,3 dimethylurea, 1:1 picrate/ 4-methyl-morfoline-N-oxide, 1:2 picrate/3-picoline-N-oxide, 1:2 picrate/glycine, 1:1 picrate/proline. Those compositions were characterized by elemental analysis (CHN) for the stoichiometry confirmation, melting points and, for the picrate/proline cocrystal, the emission and excitation spectra were recorded. It was observed that this compound is transparent above 500 nm, being therefore suitable to experiments of Nd/YAG laser radiation duplication (λ = 1.064 nm), since it does not absorb at the wavelength of the duplicated radiation (λ = 532 nm). Data collection for crystalline structure determination\'s was accomplished in an Enraf-Nonius CAD4 Mach 3 diffractometer. The observed intensities were transformed into structure factors observed through Lp and absorption corrections. The structures were determined using the direct method and refined by successive Fourier-difference calculations and least-square analysis. At the end of this determination some hydrogen bonds, O-H ...O, N-H ...O and C-H ...O could be analyzed. Those hydrogen bonds were geometrically analysed with relation to bond distances and angle, and they were also nominated and classified by the Graph-set method. Through these analyses it was possible a comparison among the structures and to common patterns in relation to intermolecular bonds. It was observed that the stronger hydrogen bonds are those formed between the donor group and the phenolic picrate oxygen. The O-H ...O (phenolic oxygen) distances d(H ...O) are concentrated in range 1.51 and 1.82 Å, and angles <OHO are concentrated between 161 and 171Å. The distances d(O...O) are between 2.48 and 3.1 Å. The distances of hydrogen bonds O-H ...O (nitro group oxygen), d(H ...0), are in the range 2.41 and 2.54 Å and angles <OHO between 100 and 121º. It is also observed that distances d(O ...O) lie between 2.78 and 3.04 Å. but predominantly they are in the interval between 2.4 and 2.55 Å. For interactions of the type N-H ...O. it is observed that distances d(H ...O) are between 1.85 and 2.52 Å, and angles <NHO, are between 121 and 171º. A quite wide area is observed with relation to the distance d(N ...O), that lie between 2.6 and 3.2 Å. For interactions of the type C-H ...O. it is observed that distances d(H ...O) increase in function of the angle <CHO; they lie between 2.96 and 3.61 Å.

PART I RESOLUTION AND DESYMMETRISATION Chapter I. ‘A Novel Racemate Resolution’. This describes a novel resolution strategy as applied to racemic α-amino acids in the solid state. The strategy is based on the possibility that second order asymmetric transformations (SOAT) would be more likely in the case of achiral molecules that form chiral crystals (i.e. a non- centrosymmetric space group).1 In such cases, a fundamental requirement of SOAT – that the molecules racemise in solution prior to crystallization – is obviated. Furthermore, the resulting enantiomerically-enriched crystals may be employed to effect a solid-state kinetic resolution of a different racemate (composed of chiral molecules). This strategy was explored with crystalline succinic anhydride (1, Scheme 1), which not only exists in a non-centrosymmetric space group (P212121) but also possesses reactive functionality to effect the resolution step.2 Thus, a finely-ground mixture of 1 (0.5 eqiv.) and a racemic α-amino acid (2, 1.0 eqiv.) was heated at ~ 70 oC over ~ 5 h without solvent. The resulting N-succinoyl derivative (3) was separated from the unreacted 2, which was found to possess significant levels of optical purity (typically ~ 70%). The strategy was applied to several common α-amino acids, the results being summarized in Table 1. These results, apart from establishing ‘proof-of-concept’ and the viability of the resolution strategy, indicate that crystalline succinic anhydride (1) is enantiomerically enriched as originally hypothesized. Chapter II. ‘Enantiospecific Alkylation and Desymmetrisations’. This deals with two enolate-mediated strategies of asymmetric synthesis: one describes approaches towards the alkylation of the stereogenic centre in benzoin without loss of stereogenicity (Section A), and the other the desymmetrisation of a meso tartarate derivative with a chiral base catalyst (Section B). Section A. This describes exploratory studies aimed at achieving the enantiospecific α-alkylation of optically-active benzoin (4, Scheme 2) via its enolate anion 5. The strategy depends on the possibility that 5 would exist in atropisomeric forms, because of steric interactions between the vicinal phenyl groups. (This is indicated in the crystal structure of the analogous enediol carbonate derived from racemic 4.)3 In such a case, remarkably, 5 would be chiral, despite its planar enediolate core! Thus, possibly, the configurational chirality in 4 (by virtue of the C2 stereogenic centre) would be transformed to the helical chirality in 5 (by virtue of the atropisomerism). Furthermore, enantioface-selective alkylation of 5 with achiral alkylating agents would, in principle, be possible. Preliminary studies were then directed towards establishing that controlled deprotonation of optically-active 4, followed by the protonation of the resulting enediolate 5, leads back to the original 4. (+)-Benzoin (4) was prepared via resolution,4 and deprotonated with KH in THF.5 The resulting enediolate (5) was neutralized with acetic acid at -70 oC/THF to recover 4, but with insignificant levels of optical activity (e.e. ~ 12%). The results possibly indicate that ortho-substituted benzoin analogs may show greater retention of chirality upon deprotonation, as the racemisation of the enediolate atropisomers would be suppressed by steric hindrance between the aryl moities. Section B. This describes studies directed towards the catalytic desymmetrisation of meso dimethyl tartarate (6, Scheme 3). The strategy involves the formation of the acetonide derivative 7 and its regioselective α-deprotonation with a chiral base catalyst. The enantioface-selective protonation of the resulting enolate (8) would lead to the chiral analog 9. The overall sequence offers a possible alternative to catalytic deracemisation, which is normally unviable for thermodynamic reasons.6 The above strategy hinges on the meso derivative 7 being thermodynamically less stable than the enantiomeric 9, which would thus be favoured at equilibrium. In fact, this is likely as the eclipsing interactions between the syn ester moieties in 7 would be relieved in 9, in which the ester moieties are anti. However, deprotonation of 7 at the other α position would compete to varying extents, depending on the selectivity induced by the chiral base. At total equilibrium, the sequence would occur via deprotonation at both α sites at equal rates, and no net optical induction would be observed. (This is a thermodynamic requirement via the principle of microscopic reversibility.) Thus, the success of the above strategy depends on stalling the deprotonation-protonation sequence at a quasi-equilibrium stage involving only one of the enantiomers (9).6 The other operational requirement was the compatibility of the pKa’s of 7 and the chiral base employed: too low a pKa of the base would result in inefficient deprotonation and slow overall rate, but a high pKa would generate a large quantity of the enolate 8 at equilibrium. After due consideration, the lithiated chiral fluorene derivative 11 (pKa ~ 22) was chosen as the chiral base catalyst [11 was prepared from fluorene (10) as indicated]. Treating 7 with 0.2 equivalent of 10 in THF at -65 oC over 2 h, led to the formation of a mixture of 7 and 9 in a 45:55 ratio (isolated in 85% total yield). Chromatographic separation of the mixture led to the isolation of pure (+)-9, which was identified spectrally; it was found to possess [α]D24 = +21.84 (c 1.0, CHCl3), corresponding to e.e. = 64%. (This implies the indicated (4S, 5S) configuration for 1, 3-dioxolane 9, as previously reported.)7 These results, despite the moderate e.e. levels obtained, indicate the viability of the above catalytic desymmetrisation strategy, bearing in mind the mechanistic ambiguities mentioned above. PART II SYNTHESES OF ALDEHYDES AND AMINO ACIDS Chapter III. ‘An Asymmetric Synthesis of Aldehydes’. This describes an oxazoline approach to the synthesis of chiral aldehydes. The oxazoline methodology for the synthesis of homochiral α-alkylated carboxylic acids is well known,8 and it was of interest to adapt this to the synthesis of the corresponding aldehydes. Essentially, it was envisaged that the reaction sequence could be diverted towards aldehydes via reduction of the alkylated oxazoline intermediate (Scheme 4). Thus, 2-ethyl-4(S)-methoxymethyl-5(R)-phenyl-1,3-oxazoline (12) was deprotonated with lithium diisopropylamide in THF, and the resulting anion treated with various alkyl halides, in the reported manner.8 The resulting alkylated product (13) was N-methylated with MeI in refluxing MeNO2 over 6 h, to obtain the quaternary salt 14. This was reduced with NaBH4 in MeOH to obtain the expected N- methyl oxazolidine 15, which was hydrolyzed in refluxing aqueous oxalic acid to the free aldehydes 16. These were isolated in moderate yields and e.e. values as shown. Chapter IV. ‘A Darzens Route to α-Amino Acids’. This describes a novel route to α-amino acids, based on the classical Darzens glycidic ester synthesis.9 In this approach (Scheme 5), the glycidic ester (19) was prepared from benzaldehyde (17) and t-butyl bromoformate (18), with KOH in THF as base, and tetrabutylammonium bromide (TBAB) as phase transfer catalyst.9b The oxirane ring in 19 was cleaved via nucleophilic attack with an amine (20), to furnish the two regio-isomeric hydroxy- amino acids (21) and (22). Generally, the β-hydroxy-α-amino acid product (21) predominated over the α-hydroxy-β-amino acid product (22), the two being separated chromatographically. The hydroxyl group in 21 was reductively cleaved via its xanthate derivative (23), by refluxing it in toluene with AIBN (10 mol %) over 4 h. The resulting α-amino acid derivatives (24) were obtained in moderate yields (< 60 %) upon chromatographic purification. (The β-amino analog 22, would lead to the corresponding β-amino acid, but this was not pursued further.) This strategy lends itself to creating structural diversity at the β-centre in the α- amino acid, drawing upon the wide scope of the well-established Darzens condensation reaction. Also, the introduction of the amino moiety is facilitated by the enhanced reactivity at the α-centre of the oxirane ring in the glycidic ester (19), presumably for both electronic and steric reasons.

Applications of conjugated polymer (CPs) in optoelectronic devices are critically depend on nature of thin film morphology. In thin film of CPs, the distribution of conjugation length is highly heterogeneous because of conformational defects, distortions of polymer chain and aggregates. A greater understanding of the self-assembly properties of polymer in solution, in particular control over aggregation leads to richer description of electronic properties and hence reproducible fabrication of thin film devices. Recently, chiral CPs have attracted profound interest because of their promising chiroptical properties in thin films and easy control over the selective agglomeration process. In this thesis, we have investigated the role of chiral side-chains on a series of thiophene diketopyrrolopyrrole (TDPP)-benzodithiophene (BDT) based copolymers. Chiral 3,7-dimethyloctyl chain was introduced as an asymmetric chain to incorporate chirality on one of the repeating unit (TDPP) of copolymers. Two polymers with side-chains of identical chirality (S),(S)-PTDPP-BDT; (R),(R)-PTDPP-BDT and a third polymer with similar side-chains of opposite chirality (R),(S)-PTDPP-BDT were synthesized. The chiroptical properties were investigated by UV-visible and circular dichroism (CD) spectroscopy. Figure 1: The structure of the TDPP-BDT copolymers. The copolymers dissolved in a good solvent (e.g. chloroform, chlorobenzene) in which polymers adopts random coil conformation, no chiral response has been observed. However, a critical addition of non-solvent (methanol), the copolymers stack in a chiral fashion and leads to typical bisignate Cotton effects. It is noteworthy that the two polymers, (S),(S)-PTDPP-BDT and (R),(R)-PTDPP-BDT exhibiting a nearly ideal mirror-image relationship in CD spectra (Figure 2a) whereas the (R),(S)-PTDPP-BDT lacks chiropticity even with the addition of methanol. The aggregation induced CD phenomena are dependent on the temperature of solution and do not exhibit reversibility in a heating-cooling cycle. Figure 2: (a) The mirror image Cotton effects of (S),(S)-PTDPP-BDT and (R),(R)-PTDPP-BDT (b) No CD signal was observed for the (R),(S)-PTDPP-BDT polymer. Figure 3: The variation of (a) UV-vis and (b) CD spectra of (R),(R)-PTDPP-BDT polymer with thickness of the solid film. To investigate the role of thickness and annealing temperature on optical and chiroptical properties of polymer films, thin films were prepared using drop-casting method from a solution of chlorobenzene. Both the polymer showed gradual enhancement of CD signal with the increase of film thickness but we did not see any such order with temperature (Figure 3). Figure 4: The morphology observed for the film by (a) AFM; (b); (c) FESEM. The thin film morphology of polymers is characterized by atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM) (Figure 4). AFM studies show the polymer molecules self-assembled and formed interconnected nanofibers. Whereas FESEM images clearly revealed that, the nanofibers of polymers are predominantly stack in a chiral fashion and mimic a one-handed helix which leads to bisignate Cotton effects. The (S),(S)-PTDPP-BDT and (R),(R)-PTDPP-BDT form fibers with opposite handedness whereas (R),(S)-PTDPP-BDT do not have such preferred handedness. The research described in this thesis aims to explore the role of chiral side-chains to impose chiral stacking and hence resulting chiral expression. Chirality in this class of polymers may endows them promising optoelectronic properties. (For figures pl see the abstract pdf file)

No / Forumla chem. . A variety of 5-chloro-2(H)-1,4-oxazin-2-ones bearing a range of substituents at their 3- and 6-positions undergo Diels-Alder cycloaddition as a 2-azadiene component with electron-rich, electron-deficient, and electron-neutral dienophiles. These reactions proceed with moderate regio- and stereoselectivity to afford relatively stable and readily isolable bridged bicyclic lactone cycloadducts. Chemical manipulation of these cycloadducts affords highly substituted and functionally rich piperidines. The regio- and stereochemical preferences of the cycloadditions of 5-chloro-2(H)-1,4-oxazin-2-ones are investigated computationally using density functional theory (B3LYP/6-31G*).