Ketenimines Generated from Ynamides: Versatile Building Blocks for Nitrogen-Containing Scaffolds

International audienceUsing ynamides as readily available starting materials, a single step can generate highly reactive ketenimines which can then undergo a variety of transformations. The choice of the method for generating the ketenimine dictates the outcome of the reaction that can, moreover, be precisely steered through minor variations of the starting material. This Concept gives an overview of the different existing methodologies for this objective, showcasing the diverse nitrogen-containing frameworks that can be obtained by this highly versatile strategy

Halonium-Induced Polyene Cyclizations

International audienceThis review covers the methods that chemists have developed to access halogenated polycyclic structures from polyenes, by emulating Nature's enzymatic machineries. From pioneering studies to the most recent developments, the different strategies, whether based on the use of standard reagents or on the design of specific ones, will be presented. Finally, asymmetric reactions and applications for the total synthesis of natural products will be exposed

Iodine(III)-mediated halogenations of acyclic monoterpenoids

International audienceFive different halofunctionalizations of acyclic monoterpenoids were performed using a combination of a hypervalent iodine(III) reagent and a halide salt. In this manner, the dibromination, the bromo(trifluoro)acetoxylation, the bromohydroxylation, the iodo(trifluoro)acetoxylation or the ene-type chlorination of the distal trisubstituted double bond occurred with excellent selectivity and moderate to good yields. 110

Synthesis of Orthogonally N-Protected, C-4 Functionalized Cyclic Guanidines from L-Serine

International audienceA straightforward and efficient preparation of 5-membered cyclic guanidines bearing an ester, a hydroxymethyl or a Weinreb amide functional group at C-4 is described from L-serine. The novel synthetic route provides cyclic guanidines in which the three nitrogen atoms are orthogonally protected making them highly suitable for further transformations into natural products or their analogues via the introduced functional groups

Towards Ruthenium(II)‐Rhenium(I) Binuclear Complexes as Photosensitizers for Photodynamic Therapy

The search for new metal‐based photosensitizers (PSs) for anticancer photodynamic therapy (PDT) is a fast‐developing field of research. Knowing that polymetallic complexes bear a high potential as PDT PSs, in this study, we aimed at combining the known photophysical properties of a rhenium(I) tricarbonyl complex and a ruthenium(II) polypyridyl complex to prepare a ruthenium‐rhenium binuclear complex that could act as a PS for anticancer PDT. Herein, we present the synthesis and characterization of such a system and discuss its stability in aqueous solution. In addition, one of our complexes prepared, which localized in mitochondria, was found to have some degree of selectivity towards two types of cancerous cells: human lung carcinoma A549 and human colon colorectal adenocarcinoma HT29, with interesting photo‐index (PI) values of 135.1 and 256.4, respectively, compared to noncancerous retinal pigment epithelium RPE1 cells (22.4)

Structurally Simple Osmium(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy in the Near Infrared**

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7‐diphenyl‐1,10‐phenanthroline)$_{2}$L]$^{2+}$ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L. Thanks to the pronounced π‐extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near‐infrared (NIR) region (up to 740 nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740 nm. The complex [Os(4,7‐diphenyl‐1,10‐phenanthroline)$_{2}$(2,2′‐bipyridine)]$^{2+}$ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor‐bearing BALB/c mice also indicate that the Os$^{II}$ complexes could significantly reduce tumor growth following 740 nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment

Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction

BACKGROUND Vasopressor agents could have certain specific effects in patients with cardiogenic shock (CS) after myocardial infarction, which may influence outcome. Although norepinephrine and epinephrine are currently the most commonly used agents, no randomized trial has compared their effects, and intervention data are lacking. OBJECTIVES The goal of this paper was to compare in a prospective, double-blind, multicenter, randomized study, the efficacy and safety of epinephrine and norepinephrine in patients with CS after acute myocardial infarction. METHODS The primary efficacy outcome was cardiac index evolution, and the primary safety outcome was the occurrence of refractory CS. Refractory CS was defined as CS with sustained hypotension, end-organ hypoperfusion and hyperlactatemia, and high inotrope and vasopressor doses. RESULTS Fifty-seven patients were randomized into 2 study arms, epinephrine and norepinephrine. For the primary efficacy endpoint, cardiac index evolution was similar between the 2 groups (p = 0.43) from baseline (H0) to H72. For the main safety endpoint, the observed higher incidence of refractory shock in the epinephrine group (10 of 27 [37%] vs. norepinephrine 2 of 30 [7%]; p = 0.008) led to early termination of the study. Heart rate increased significantly with epinephrine from H2 to H24 while remaining unchanged with norepinephrine (p <0.0001). Several metabolic changes were unfavorable to epinephrine compared with norepinephrine, including an increase in cardiac double product (p = 0.0002) and lactic acidosis from H2 to H24 (p <0.0001). CONCLUSIONS In patients with CS secondary to acute myocardial infarction, the use of epinephrine compared with norepinephrine was associated with similar effects on arterial pressure and cardiac index and a higher incidence of refractory shock. (Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock [OptimaCC]; NCT01367743) (J AmColl Cardiol 2018; 72: 173-82) (C) 2018 by the American College of Cardiology Foundation.Peer reviewe

Essay on force majeure

La force majeure est au cœur des tensions qui traversent le système juridique. Indissociable du principe de responsabilité au fondement de l’ordre juridique, la force majeure, pour être appréhendée dans son essence et son unité, devait être abordée dans le cadre d’une étude générale et transversale. A l’échelle de la norme juridique, elle révèle sa nature d’exception propre à neutraliser toute norme prescriptive. A l’échelle du destinataire de la norme, elle interroge le rapport de contrainte qui les unit. Replacée dans une théorie plus globale de la justification, la force majeure peut elle-même faire l’objet d’une théorie générale qui permettra d’assurer son unité notionnelle et son application cohérente dans l’ensemble de l’ordre juridique, afin de surmonter le désordre qui caractérise le droit contemporain.Force majeure is at the heart of the tensions that run through the legal system. Indissociable from the principle of responsibility at the foundation of the legal order, force majeure, in order to be understood in its essence and unity, must be placed in a global and transversal study. At the level of the legal norm, it reveals its nature as an exception capable of neutralizing any prescriptive norm. At the level of the addressee of the norm, it questions the relationship of constraint that unites them. Placed in a more global theory of justification, force majeure can itself be the object of a general theory which will make it possible to ensure its notional unity and its coherent application in the whole of the legal order, and to overcome the disorder which characterises contemporary law

Photoinduced Aerobic Iodoarene-Catalyzed Spirocyclization of N-Oxy-Amides to N-Fused Spirolactams

Using the spiro-cyclization of amides as a model reaction we have demonstrated that aerobic iodoarene catalysis can be enabled by relying on a pyrylium photocatalyst under blue light irradiation. This unprecedented dual organocatalytic system allows the use of low catalytic loading of both catalysts under very mild operating conditions.<br /

Synthetic approaches towards avibactam and other diazabicyclooctane β-lactamase inhibitors

International audienceAvibactam is a non β-lactam β-lactamase inhibitor that has recently been approved in association with a β-lactam antibiotic for the treatment of severe infections caused by otherwise resistant bacteria. Its therapeutic success encouraged the development of many congeners based on its particular diazabicyclooctane scaffold. This review presents a detailed overview of the synthetic strategies that have been implemented to acces these complex bicyclic compounds with a particular focus on those that are currently on the market or in clinical trials