1,6-Conjugate Additions of Carbon Nucleophiles to 2-[(1E,3E)-4-Arylbuta-1,3-dien-1-yl]-4H-chromen-4-ones

KGaA, Weinheim The 1,6-conjugate addition of nitromethane to 2-[(1E,3E)-4-arylbuta-1,3-dien-1-yl]-4H-chromen-4-ones was accomplished and led mainly to the corresponding β-(nitromethyl)chromones. (E)-5′-(Nitromethyl)-3′-styryl-[1,1′-biphenyl] -2-ol and 3′-aryl-2′-nitro-5′-(nitromethyl)spiro[chromane-2,1′-cyclohexan]-4-one derivatives were also isolated as minor products from tandem processes, which result from the addition of a second molecule of nitromethane. The nucleophile scope was investigated with malononitrile, acetylacetone, ethyl cyanoacetate, and diethyl malonate, which gave the expected 1,6-addition products; in the last case, it was also possible to isolate a minor product formed through a 1,8-/1,6-addition sequence. Computational calculations provided a rationale for the experimental reactivity of carbon nucleophiles with 2-[(1E,3E)-4-arylbuta-1,3-dien-1-yl] -4H-chromen-4-ones. The further functionalization of some adducts allowed the preparation of new nitrogen-containing heterocyclic compounds, such as new styrylpyrrolidines and new pyrazole and bis(pyrazole) derivatives.Thanks are due to the University of Aveiro and Fundação para a Ciência e a Tecnologia (FCT)/Ministerio de Educación y Ciencia (MEC) for the financial support of the QOPNA research unit (FCT UID/QUI/00062/2013) through national funds and, where applicable, cofinanced by Fundo Europeu de Desenvolvimento Regional (FEDER) within the PT2020 Partnership Agreement, and to the Portuguese NMR Network as well as the Instituto Politécnico de Bragança. H. M. T. A. is grateful to Fundação para a Ciência e a Tecnologia (FCT) for his PhD grant (SFRH/BD/86277/ 2012).info:eu-repo/semantics/publishedVersio

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

(Mis)matching Metadata: Improving Accessibility in Digital Visual Archives through the EyCon Project

Discussing the current AHRC/LABEX-funded EyCon (Early Conflict Photography 1890-1918 and Visual AI) project, this article considers potentially problematic metadata and how it affects the accessibility of digital visual archives. The authors deliberate how metadata creation and enrichment could be improved through Artificial Intelligence (AI) tools and explore the practical applications of AI-reliant tools to analyse a large corpus of photographs and create or enrich metadata. The amount of visual data created by digitisation efforts is not always followed by the creation of contextual metadata, which is a major problem for archival institutions and their users, as metadata directly affects the accessibility of digitised records. Moreover, the scale of digitisation efforts means it is often beyond the scope of archivists and other record managers to individually assess problematic or sensitive images and their metadata. Additionally, existing metadata for photographic and visual records are presenting issues in terms of out-dated descriptions or inconsistent contextual information. As more attention is given to the creation of accessible digital content within archival institutions, we argue that too little is being given to the enrichment of record data. In this article, the authors ask how new tools can address incomplete or inaccurate metadata and improve the transparency and accessibility of digital visual records

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