Practical Access to Aromatic Thiocyanates by CuCN-Mediated Direct Aerobic Oxidative Cyanation of Thiophenols and Diaryl Disulfides

International audienceThe practical and mild aerobic oxidative CuCN-mediated cyanation of thiophenols and diaryl disulfides was investigated. The reaction was performed in air at room temperature and reached aromatic thiocyanates in moderate to good yields starting from a broad range of diversely functionalized substrates

Comparative study on the reactivity of propargyl and alkynyl sulfides in palladium-catalyzed domino reactions

International audienceThree types of sulfides bearing a propargyl or an alkynyl moiety have been studied in cyclocarbopalladation/cross-coupling domino palladium-catalyzed sequences. The reactivity of different types of sulfured starting materials has been compared as well as the difference in behavior of these compounds depending on the type of cross coupling ending the domino sequence. It appeared that these cascades were constantly more efficient on the propargyl benzyl thioether. In addition, it has been demonstrated that domino sequences ending with Stille, SuzukieMiyaura, or MizorokieHeck lead efficiently and selectively to the desired cyclized products. Notably, when the introduction of an alkyne is targeted at the end of the cascade, it appeared that the Sonogashira coupling leads every time to the desired cyclic product in the mixture with the product resulting from the direct coupling between the aryl moiety of the substrate and the alkyne used as partner. Finishing the domino sequence with a Stille coupling instead of a Sonogashira one allowed improving significantly the ratio of the mixture in favor of the desired cyclized compound

Réalisation d'un dispositif expérimental pour l'étude des réactions de captures radiatives induites sur le lithium

Le dispositif décrit consiste en un évaporateur de lithium et un « vobulateur de position de cible ». L'évaporateur nous permet de préparer in situ des cibles exemptes de contaminations. Le « vobulateur » fait décrire à la cible une courbe de Lissajous par rapport au faisceau afin d'éviter la surchauffe de la cible

Aerobic Copper-Mediated Domino Three-Component Approach to 2-Aminobenzothiazole Derivatives

An unprecedented three-component reaction involving a 2,2′-diaminodiaryl disulfide, copper cyanide, and an electrophile is described. This transformation is based on an oxidative copper-mediated S-cyanation as a key step and involves a cyanation/cyclization/acylation domino sequence enabling a rapid and efficient synthesis of diversely substituted 2-aminobenzothiazole derivatives. Notably, this reaction proceeds via an original mechanism involving an intermolecular migration of the acyl group

Diastereoselective Synthesis of Novel Aza-diketopiperazines via a Domino Cyclohydrocarbonylation/Addition Process

Herein, we report an unprecedented, short and diastereo-selective synthesis of newly reported aza-diketopiperazine (aza-DKP) scaffolds starting from amino acids. The strategy is based on a Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation of allyl-substituted aza-DKP, followed by a diastereoselective functionalization of the platform. This methodology allows the synthesis of novel bicyclic and tricyclic aza-DKP scaffolds incorporating six- or seven-membered rings, with potential applications in medicinal chemistry

Guidance on quantitative pest risk assessment

This Guidance describes a two-phase approach for a fit-for-purpose method for the assessment of plant pest risk in the territory of the EU. Phase one consists of pest categorisation to determine whether the pest has the characteristics of a quarantine pest or those of a regulated non-quarantine pest for the area of the EU. Phase two consists of pest risk assessment, which may be requested by the risk managers following the pest categorisation results. This Guidance provides a template for pest categorisation and describes in detail the use of modelling and expert knowledge elicitation to conduct a pest risk assessment. The Guidance provides support and a framework for assessors to provide quantitative estimates, together with associated uncertainties, regarding the entry, establishment, spread and impact of plant pests in the EU. The Guidance allows the effectiveness of risk reducing options (RROs) to be quantitatively assessed as an integral part of the assessment framework. A list of RROs is provided. A two-tiered approach is proposed for the use of expert knowledge elicitation and modelling. Depending on data and resources available and the needs of risk managers, pest entry, establishment, spread and impact steps may be assessed directly, using weight of evidence and quantitative expert judgement (first tier), or they may be elaborated in substeps using quantitative models (second tier). An example of an application of the first tier approach is provided. Guidance is provided on how to derive models of appropriate complexity to conduct a second tier assessment. Each assessment is operationalised using Monte Carlo simulations that can compare scenarios for relevant factors, e.g. with or without RROs. This document provides guidance on how to compare scenarios to draw conclusions on the magnitude of pest risks and the effectiveness of RROs and on how to communicate assessment results

Kaposi's Sarcoma Herpesvirus microRNAs Target Caspase 3 and Regulate Apoptosis

Kaposi's sarcoma herpesvirus (KSHV) encodes a cluster of twelve micro (mi)RNAs, which are abundantly expressed during both latent and lytic infection. Previous studies reported that KSHV is able to inhibit apoptosis during latent infection; we thus tested the involvement of viral miRNAs in this process. We found that both HEK293 epithelial cells and DG75 cells stably expressing KSHV miRNAs were protected from apoptosis. Potential cellular targets that were significantly down-regulated upon KSHV miRNAs expression were identified by microarray profiling. Among them, we validated by luciferase reporter assays, quantitative PCR and western blotting caspase 3 (Casp3), a critical factor for the control of apoptosis. Using site-directed mutagenesis, we found that three KSHV miRNAs, miR-K12-1, 3 and 4-3p, were responsible for the targeting of Casp3. Specific inhibition of these miRNAs in KSHV-infected cells resulted in increased expression levels of endogenous Casp3 and enhanced apoptosis. Altogether, our results suggest that KSHV miRNAs directly participate in the previously reported inhibition of apoptosis by the virus, and are thus likely to play a role in KSHV-induced oncogenesis

Stratégies de synthèse d'azafenestradiènes et d'azacyclooctatriènes

Nous avons étudié des accès possibles à de deux nouvelles familles de molécules qui sont les azacyclooctatriènes et les [6.4.6.4] azafenestradiènes en utilisant une nouvelle méthodologie de synthèse : la réaction d azaélectrocyclisation à huit électrons p, qui à notre connaissance n a jamais été décrite à ce jour. Après quelques étapes de synthèse initiées par la réaction de cyclocarbopalladation 4-exo-dig, nous avons pu accéder à différents intermédiaires clés tels que les azatriènynes et les azatétraènes qui nous ont permis d étudier la faisabilité de la réaction d azaélectrocyclisation. Différents paramètres ont été étudiés, notamment les conditions de température, l ajout de métaux de transition en quantité catalytique ainsi que l introduction de groupements électroattracteurs sur les différentes positions du squellette de l azocine. Cette étude nous a permis d établir quelques paramètres utiles à la poursuite de la mise au point de la réaction d azaélectrocyclisation.We have studied possibles access to two new molecular families that are azacyclooctatrienes and [6.4.6.4]azafenestradienes by using a new synthesis methodology : the 8p azaelectrocylization which, for now has never been described to our knowledge. After few synthetic steps initiated by the 4-exo-dig cyclocarbopalladation, we have obtained different key intermediates as azatrienynes and azatetraenes in order to study the feasibility of the azaelectrocyclization. The influence of differents parameters have been studied in particular the temperature, catalytic addition of transition metal and the introduction of an electron-withdrawing group in different position of the azocine skeleton. By this study, we established some useful parameters to continue the understanding of azaelectrocyclization feasibility.STRASBOURG-Bib.electronique 063 (674829902) / SudocSudocFranceF

Cyclocarbopalladations 4-exo-dig et 5-exo-dig (une solution expéditive vers la complexité moléculaire ?)

Les réactions de catalyse au palladium appliquées en synthèse organique sont loin d avoir été totalement explorées. L utilisation de stratégies de cyclisation palladocatalysée pour élaborer de nouveaux squelettes carbonés polycycliques, et ceci de manière régiosélective et stéréosélective, s est avérée très efficace par le passé. Les réactions de cyclisations intramoléculaires, qui conduisent à l attaque de triples liaisons par ces espèces organopalladiées, sont d une efficacité redoutable. Dans la majorité des cas, l initialisation des réactions par cyclocarbopalladation de type de 5-exo-dig, 6-exo-dig, 7-exo-dig, sont terminées par le couplage direct d espèces organométalliques ou de nucléophiles. Au cours de cette étude, nous avons entrepris le développement de nouvelles méthodologies de cyclocarbopalladation en partant de substrats très simples. Les principales investigations ont été effectuées sur la réaction tandem de cyclocarbopalladation 4-exo-dig et 5-exo-dig. Nos travaux initiaux se sont focalisés sur la réaction tandem de cyclocarbopalladation 4-exo-dig suivi d un couplage de Stille pour obtenir des cyclobutanes polyfonctionnalisés retrouvés dans un grand nombre de substances biologiques. Les étendues de cette réaction et ses limites ont été ensuite entreprises avec succès. D autres approches ont été considérées afin d ajouter un élément à la séquence réactionnelle. Il est tout à fait possible de commencer par la cyclocarbopalladation 4-exo-dig et de terminer par un couplage de Suzuki ou une réaction de Heck intramoléculaire. En parallèle, et aux vues des résultats antérieurs sur la cyclocarbopalladation 5-exo-dig, nous avons combiné cette dernière avec une activation CH aromatique. Au départ des diols b-bromo propargyliques aromatiques, des produits de substitution aromatique ont été obtenus. La migration 1,5 du palladium par activation CH explique de tels résultats sans précédent dans la littérature. Une recherche de ses limites et de ses étendues a permis de découvrir la substrat-dépendance de cette réaction.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF