Literatura académica sobre el tema "Multicatalysis"

La catalyse asymétrique est un outil fondamental pour la synthèse de molécules chirales, indispensables en chimie organique et en pharmacie. Ce travail de thèse explore de nouvelles stratégies impliquant la catalyse à l'Au(I), reconnue pour sa capacité unique à activer les liaisons insaturées et à former des liaisons C-C, C-N ou C-O. Une première partie des travaux s'est concentrée sur le développement de transformations auro-catalysées énantiosélectives, et notamment à leur application dans le développement de réactions de spirocyclisations stéréosélectives en milieu micellaire, ouvrant de nouvelles perspectives pour la synthèse de motifs hétérocycliques chiraux.L'essentiel des recherches s'est ensuite focalisé sur le développement de séquences multicatalytiques combinant la catalyse à l'or(I) avec la biocatalyse dans le cadre du projet ANR BiAuCat. Cette approche novatrice exploite les avantages complémentaires des deux systèmes : l'Au(I) pour les activations chimiques de liaisons multiples et les enzymes pour leur haute sélectivité. Ces cascades réactionnelles ont permis la synthèse d'amines chirales à l'aide de transaminases à partir de substrats simples, ouvrant des perspectives intéressantes pour la création rapide de molécules bioactives et de motifs hétérocycliques.Le développement de ces stratégies a toutefois présenté plusieurs défis. L'incompatibilité potentielle des conditions optimales pour la catalyse à l'or et la biocatalyse (pH, température, solvants) a nécessité des ajustements précis des protocoles expérimentaux pour garantir la sélectivité des réactions tout en conservant une efficacité catalytique élevée. Dans l'ensemble, ce travail met en lumière l'énorme potentiel des combinaisons multicatalytiques pour surmonter les limitations des approches traditionnelles. Il ouvre ainsi de nouvelles perspectives en synthèse asymétrique et dans le domaine de la chimie verte, avec des applications prometteuses dans la conception de molécules chirales complexes à haute valeur ajoutée<br>Asymmetric catalysis is a fundamental tool for synthesizing chiral molecules, which are widely used in organic chemistry and pharmacy. This thesis explores new strategies involving Au(I) catalysis, recognized for its unique ability to activate unsaturated bonds and form C-C, C-N, or C-O bonds. Special attention was given to the use of bifunctional Au(I) complexes which were used in asymmetric transformations, particularly in the development of stereoselective spirocyclization reactions in micellar media, opening new avenues for the synthesis of chiral heterocyclic motifs.The main research focus then shifted to developing multicatalytic sequences combining Au(I) catalysis with biocatalysis within the framework of the ANR BiAuCat funded project. This novel approach leverages the complementary advantages of both systems: Au(I) for complex chemical activations and enzymes for their high selectivity. These reaction cascades enabled the synthesis of chiral amines using transaminases from simple substrates, offering exciting prospects for the rapid access to bioactive molecules and heterocyclic motifs.The development of these strategies presented several challenges. The potential incompatibility of optimal conditions for Au(I) catalysis and biocatalysis (pH, temperature, solvents) required precise adjustments to experimental protocols to ensure reaction selectivity while maintaining high catalytic efficiency. Overall, this work highlights the immense potential of multicatalytic combinations to overcome the limitations of traditional approaches. It opens new perspectives in asymmetric synthesis and green chemistry, with promising applications in the design of high-value-added complex chiral molecules

Les groupements alcooliques sont présents dans une grande diversité de produits chimiques fins précieux issus de la nature et de la synthèse, c'est pourquoi les méthodes permettant leur diversification structurelle sont recherchées. Cependant, la modification de la structure des alcools à certaines positions non réactives, même avec l'aide de la catalyse, reste un défi ou nécessite des procédures multi-étapes fastidieuses et souvent coûteuses. Récemment, une attention accrue a été accordée à la multicatalyse, qui combine plusieurs catalyseurs au sein d'un même système, ce qui permet de découvrir des réactivités auparavant inaccessibles ou d'accroître l'efficacité globale des transformations en plusieurs étapes. Les méthodes décrites ici permettent l'α- et la β-arylation diastéréo- et énantiosélective d'alcools. En combinant des catalyseurs à base de Ru et de Pd, il est possible de réaliser une β-arylation énantiosélective (et diastéréodivergente dans le cas d'alcools portant déjà des stéréocentres) sans précédent d'alcools primaires. En outre, dans le cadre d'une catalyse relais séquentielle, il est possible d'obtenir des alcools benzyliques secondaires enrichis enantioénergie à partir de divers produits de départ disponibles, tels que des alcools primaires ou des alcools portant une double liaison. Dans l'ensemble, ces protocoles démontrent le potentiel de la multicatalyse en tant qu'outil synthétique pour diversifier les alcools. Dans un contexte plus large, cette thèse ouvre la voie à la conception de nouvelles stratégies et méthodes multicatalytiques pour une synthèse efficace<br>Alcohol moieties are present in a great diversity of valuable fine chemicals from nature and synthesis, therefore methods enabling their structural diversification are sought after. However, modifying the structure of alcohols at certain unreactive positions, even with the aid of catalysis, remains a challenge or requires tedious often wasteful multistep procedures. Recently, increased attention has been paid to multicatalysis, which combines multiple catalysts within one system, enabling the discovery of previously inaccessible reactivities or increasing the overall efficiency of multistep transformations. Described within are methods which enable the diastereo-, and enantioselective α-, and β-arylation of alcohols. By combining Ru- and Pd-based catalysts the unprecedented, enantioselective (and diastereodivergent in the case of alcohols already bearing stereocenters) β-arylation of primary alcohols can be carried out. Also, under sequential relay catalysis enantioenriched secondary benzylic alcohols can be obtained from a variety of available starting materials, such as primary alcohols, or alcohols bearing a double bond. Overall, these protocols demonstrate the potential of multicatalysis as a synthetic tool for diversifying alcohols. In a broader context, this thesis sets the stage for devising novel, multicatalytic strategies and methods for efficient synthesis

This Doctoral Thesis is framed in the area of Sustainable Chemistry and more specifically in the field of continuous flow chemistry. The main objective has been the design and development of new continuous multicatalytic systems based on the use of supported ionic liquids, materials with very interesting catalytic properties. This objective has been applied to C-C bond forming reactions such as cyanosilylation, Strecker reaction or Negishi cross-couplings; whose products mean key synthetic intermediates in several processes in organic synthesis, specially in Fine and Pharmaceutical Chemistry. Telescopic processes and divergent syntheses have been succesfully achieved under continuous flow conditions. In addition, the novel additive manufacturing 3D printing technology has been introduced for the potential obtaining of continuous flow catalytic reactors.<br>La presente Tesis Doctoral se engloba dentro del área de la Química Sostenible y más concretamente en el campo de la química en flujo continuo. El principal objetivo es el diseño y desarrollo de nuevos sistemas multicatalíticos en continuo basados en el uso de líquidos iónicos soportados, cuyas propiedades catalíticas son muy interesantes. Este objetivo se ha aplicado a reacciones de formacion de enlaces C-C como la cianosililación, la reacción de Strecker y el acoplamiento de Negishi; cuyos productos resultan intermedios sintéticos clave en muchos procesos de síntesis orgánica, sobre todo en Química Fina y Farmacéutica. Procesos telescópicos y síntesis divergentes han sido desarrolados con éxito en continuo. Además, también se ha introducido la nueva tecnología de impresion 3D para la potencial obtención de reactores catalíticos de flujo continuo.

The multicatalytic proteinase (MCP) is a 700 kDa multisubunit complex which is found in eukaryotic cells. MCP is involved in ubiquitin-dependent non-lysosomal protein degradation and has been implicated in the processing of antigens by the major histocompatability complex class 1 pathway. The MCP purified from rat liver is composed of at least 16 distinct subunits of molecular masses between 22 and 34 kDa. MCP is known to possess at least three distinct peptidase activities, described as the 'trypsin-like', 'chymotrypsin-like' and 'peptidylglutamylpeptide hydrolase' activities. However, it is not known which subunits are responsible for the different peptidase activities. The main aims of my study were (1) to establish which subunit(s) possesses the active site responsible for 'trypsin-like' activity, (2) to identify the catalytic amino acid residues responsible for this activity and (3) to determine whether all MCP particles possess these components. 'Protection' experiments with the peptide aldehyde leupeptin, which is a specific reversible inhibitor of the 'trypsin-like' activity, have identified one or two subunits which possess thiol groups essential for 'trypsin-like' activity. These thiol groups are probably not involved in catalysis but may be located very close to the active site responsible for 'trypsin-like' activity. An active site specific peptidyl chloromethane which specifically inactivates the 'trypsinlike' activity, labels two distinct subunits of 23-24 kDa. One of these polypeptides is also labelled by an active site specific peptidyl diazomethane for the 'chymotrypsin-like' activity, in addition to three other distinct polypeptides of 28-23 kDa. Together these results suggest that one active site is responsible for 'trypsin-like' activity while four distinct active sites are responsible for 'chymotrypsin-like' activity. Affinity chromotography was carried out using an immobilised specific inhibitor of the 'trypsin-like' activity. The results of these studies suggest that all MCP particles purified from rat liver possess the catalytic component responsible for the 'trypsin-like' activity.

There is increasing concern regarding alternative, sustainable energy sources, such as biofuels, to replace declining oil reserves. The abundance of lignocellulosic biomass makes it the only imaginable resource that can potentially substitute a substantial portion of the fossil fuels we use today, but current methods for producing biofuels from non-food crops are cost intensive and not economically viable. Synthetic biology provides several potential approaches for developing biologically mediated processes for the conversion of lignocellulosic biomass into biofuels. Such systems are based on engineered microbes that produce enzymes for catalysing the conversion of cellulose into fermentable sugars and subsequently into high value products. Effective degradation of cellulose requires multiple classes of enzyme working together. In naturally occurring cellulose degrading microbes, bioconversion is catalysed by a battery of enzymes with different catalytic properties. However, naturally occurring cellulases with multiple catalytic domains seem to be rather rare in known cellulose-degrading organisms. Using synthetic biology approaches, seven cellulases with multiple catalytic domains were engineered and tested to determine the usefulness of such chimeric enzymes to replace cloning of multiple enzymes for biomass conversion. Catalytic domains were taken from Cellulomonas fimi endoglucanases CenA, CenB and CenD, exoglucanase Cex, and β-glucosidase, Cfbglu as well as Cytophaga hutchinsonii cellodextrinase CHU2268. All fusions retained both catalytic activities of the parental enzymes. To investigate the benefits of fusion, Citrobacter freundii NCIMB11490 was transformed with either fused or non-fused enzymes and cultured with cellulose blotting papers as main carbon source. Cells expressing fusions of Cex with CenA or CenD reproducibly showed higher growth than cells expressing non-fused versions, as well as more rapid physical destruction of paper. The opposite was observed for the other combinations. Comparing two different Cex and CenA fusions, CxnA2, which contains two carbohydrate binding modules (CBMs), degraded filter paper faster and led to better growth than CxnA1, which contains only one CBM. It was observed that CxnA1 was exported to the supernatant of E. coli and C. freundii cultures, as also seen for Cex and CenA, although there is no clear biological mechanism for this. Monitoring of growth using colony counts is laborious, but the use of optical density is not possible for cellulose-based cultures as it is affected by the insoluble cellulose particles. The SYBR Green I/propidium iodide live/dead staining protocol was therefore evaluated for growth measurements and was found to allow rapid measurements of large numbers of samples. In conclusion, these studies have demonstrated a simple and useful method for making chimeric proteins from libraries of multiple parts. The results demonstrate that use of fusion proteins can improve biomass conversion in vivo, and could potentially reduce the necessity for cloning of multiple enzymes and improve product yields. A simple and effective method for monitoring growth of bacteria in turbid cultures using a fluorimeter has also been developed.