Développement de transformations à économie d'atomes par cascades réactionnelles

The work presented in this manuscript aims to study organocatalyzed asymmetric reaction sequences focused on thesynthesis of polycyclic compounds. These compounds, found in some natural products, are also fluorescent.The manuscript starts with an introduction to the polycyclic molecules and the different activation means used in aminocatalysis and their combination for cascade reactions. The first chapter presents the synthesis of tricyclic indole and indazole derivatives through an aminocatalyzed enantioselective aza-Michael addition/aldolisation reaction sequence. The second chapter is dedicated to studying the solvatofluorochromic behavior of some analogues of the compounds synthesized in the first chapter as well as the influence of the various functional groups born by the molecule on these properties. The third chapter describes the synthesis of fully-carbonated tricyclic compounds starting from 2-naphthols. This aminocatalyzed and asymmetric cascade strategy rests on an Friedel-Crafts alkyltion/aldolisation sequenceLes travaux exposés dans ce manuscrit ont pour objectif d'étudier des séquences réactionnelles organocatalysées asymétriques tournées vers l'obtention de composés polycycliques. Ces composés, présents dans certains composés naturels, sont aussi fluorescents. Le manuscrit débute par une introduction sur les molécules polycycliques et les différents modes d'activation en aminocatalyse ainsi que leur combinaison dans des réactions en cascade. Le premier chapitre traite de l'obtention de dérivés tricycliques d'indole et d'indazole par une cascade réactionnelle de type addition d'aza-Michael/aldolisation aminocatalysée énantiosélective. Le deuxième chapitre vise à étudier le comportement solvatofluorochromique de quelques analogues des composés synthétisés dans le premier chapitre ainsi que l'influencedes différents groupements fonctionnels de la molécule sur ces propriétés. Le troisième chapitre décrit la synthèse decomposés tricycliques entièrement carbonés à partir de 2-naphtols. Cette stratégie en cascade aminocatalysée et asymétrique repose sur une séquence alkylation de Friedel-Crafts/aldolisation

Development of atom-efficient transformations through domino sequences

Les travaux exposés dans ce manuscrit ont pour objectif d'étudier des séquences réactionnelles organocatalysées asymétriques tournées vers l'obtention de composés polycycliques. Ces composés, présents dans certains composés naturels, sont aussi fluorescents. Le manuscrit débute par une introduction sur les molécules polycycliques et les différents modes d'activation en aminocatalyse ainsi que leur combinaison dans des réactions en cascade. Le premier chapitre traite de l'obtention de dérivés tricycliques d'indole et d'indazole par une cascade réactionnelle de type addition d'aza-Michael/aldolisation aminocatalysée énantiosélective. Le deuxième chapitre vise à étudier le comportement solvatofluorochromique de quelques analogues des composés synthétisés dans le premier chapitre ainsi que l'influencedes différents groupements fonctionnels de la molécule sur ces propriétés. Le troisième chapitre décrit la synthèse decomposés tricycliques entièrement carbonés à partir de 2-naphtols. Cette stratégie en cascade aminocatalysée et asymétrique repose sur une séquence alkylation de Friedel-Crafts/aldolisation.The work presented in this manuscript aims to study organocatalyzed asymmetric reaction sequences focused on thesynthesis of polycyclic compounds. These compounds, found in some natural products, are also fluorescent.The manuscript starts with an introduction to the polycyclic molecules and the different activation means used in aminocatalysis and their combination for cascade reactions. The first chapter presents the synthesis of tricyclic indole and indazole derivatives through an aminocatalyzed enantioselective aza-Michael addition/aldolisation reaction sequence. The second chapter is dedicated to studying the solvatofluorochromic behavior of some analogues of the compounds synthesized in the first chapter as well as the influence of the various functional groups born by the molecule on these properties. The third chapter describes the synthesis of fully-carbonated tricyclic compounds starting from 2-naphthols. This aminocatalyzed and asymmetric cascade strategy rests on an Friedel-Crafts alkyltion/aldolisation sequenc

Synthesis and fluorosolvatochromic properties of 1,7-annulated indoles

A new family of indole-based fluorescent dyes has been easily synthesized from readily available substrates. The structures of all new compounds were confirmed by NMR, IR, and HRMS and a crystallographic structure has been obtained for the 2,6-dicyanoaniline derivative 3. UV/vis absorption and photoluminescence spectroscopy analyses were performed on push-pull indole derivatives 1, 2 and 4. While the absorption maxima were almost independent of the solvent, the emission energy decreased while increasing the solvent polarity. A linear correlation between the orientation polarizability (Delta f) of the solvent and the Stokes shifts was observed and DFT calculations were carried out to study the influence of the planarity of the structures on the fluorescent quantum yields

Structural Studies of Large dsDNA Viruses using Single Particle Methods

Structural studies of large biological assemblies pose a unique problem due to their size, complexity and heterogeneity. Conventional methods like x-ray crystallography, NMR, etc. are limited in their ability to address these issues. To overcome some of these limitations, single particle methods were used. In these methods, each particle image is manipulated individually to find the best possible set of images to reconstruct the 3D structure. The structural studies in this thesis, exploit the advantages of single particle methods.  The large data set generated by the SPI study of PR772 provides better statistics about the sample quality due to the use of GDVN, a container-free sample delivery method. By analyzing the diffusion map, we see that the use of GDVNs as a sample delivery method produces wide range of particle sizes owing to the large droplet that are created.  The high-resolution structure of bacteriophage PR772 confirmed the speculation about the heteropentameric nature of the penton and revealed the new architecture of the vertex complex consisting of a hetero-pentameric penton formed with three copies of P5 and two copies of P31. The beta propeller region of P2, formed by domains I and II is bound to the N-terminal domain of P5. The structure also reveals new conformations of N-terminal and C-terminal region of P3 which play an important role in particle assembly and structural stability.  The study of Melbournevirus revealed the protein composition in a packed particle. The CryoEM structure of Melbournevirus reveals a T=309 capsid with an inner lipid membrane. A dense body was found in the viral particle, a feature not observed in other viruses of the Marseilleviridae family. The density of this body is similar to a nucleic acid-protein complex. This observation, along with the histone-like protein identified during study, suggest genome organization in the viral particle, similar to higher organisms. The soft X-ray microscope operated in the water-window shows the progression of the Cedratvirus lurbo infection in the host cell without the use of chemical fixation, staining, sample dehydration or polymer embedding. The study revealed a significant bioconversion from the host cell to the viral particle at later stages of infection

Asymmetric Synthesis of Fused Polycyclic Indazoles through Aminocatalyzed Aza-Michael Addition/Intramolecular Cyclization

The first example of an asymmetric aminocatalyzed aza-Michael addition of 1<i>H</i>-indazole derivatives to α,β-unsaturated aldehydes is described. The iminium/enamine cascade process lies at the heart of our strategy, leading to enantioenriched fused polycyclic indazole architectures. Variations on both the α,β-unsaturated aldehydes and the indazole-7-carbaldehyde heterocycles were studied in order to broaden the scope of the transformation in synthetically interesting directions. The fused polycyclic indazoles exhibit fluorescence properties and can undergo synthetic transformations

Asymmetric Synthesis of Fused Polycyclic Indazoles through Aminocatalyzed Aza-Michael Addition/Intramolecular Cyclization

The first example of an asymmetric aminocatalyzed aza-Michael addition of 1<i>H</i>-indazole derivatives to α,β-unsaturated aldehydes is described. The iminium/enamine cascade process lies at the heart of our strategy, leading to enantioenriched fused polycyclic indazole architectures. Variations on both the α,β-unsaturated aldehydes and the indazole-7-carbaldehyde heterocycles were studied in order to broaden the scope of the transformation in synthetically interesting directions. The fused polycyclic indazoles exhibit fluorescence properties and can undergo synthetic transformations

Catalytic Enantioselective [10+4]\u2005Cycloadditions

The first peri\u2010 and stereoselective [10+4]\u2005cycloaddition between catalytically generated amino isobenzofulvenes and electron\u2010deficient dienes is described. The highly stereoselective catalytic [10+4]\u2005cycloaddition exhibits a broad scope with high yields, reflecting a robust higher\u2010order cycloaddition. Experimental and computational investigations support a kinetic distribution of intermediate rotamers dictating the enantioselectivity, which relies heavily on additive effects