Synthesis of conjugated multi-ynamides by copper-catalyzed reactions

International audienceThe synthesis of multi-ynamides according to the copper-catalyzed Evano’s and Hsung’s methods is described. In these new compounds, the ynamide functions are conjugated to each other with a phenyl, a biphenyl, a thienyl or a triphenylamine space

Synthesis of ferrocenyl derivatives as novel nucleic analogue monomers

Bioorganometallic chemistry is a growing field of research in which organometallic chemistry is combined with biology to achieve novel molecules with novel properties at the biological level. In this area, the tagging of DNA with bioorganometallic molecules such as ferrocene has been the object of much attention over the past few decades. In recent years, a novel approach has been developed consisting of replacing parts of nucleic acids with organic groups including metal-binding ligands. Considering this approach, it was decided to investigate the replacement of DNA dinucleotides with a tetra-substituted ferrocenyl monomer containing nucleobases, leading to the formation of a novel nucleic acid analogue called ferrocene nucleic acid (FcNA). The synthesis of several monomers containing adenine and uracil has been the subject of this thesis. Coupling nucleobases to form bis-substituted ferrocenes was first investigated as a model for the subsequent synthesis of tetra-substituted ferrocenyl monomers with high chiral purity. The compounds were characterised using a range of spectroscopic and analytical techniques, including Xray crystallography. The influence of the nucleobases and the nature of the linker to the ferrocenyl group have also been investigated using electrochemistry

Investigation on the stoichiometry of carbon dioxide in isotope-exchange reactions with phenylacetic acids

International audienceThe functionalization of carbon dioxide (CO$_2$) as a C1 building block has attracted enormous attention. Carboxylation reactions, in particular, are of major interest for applications in isotope labeling. Due to the inexpensive nature of CO$_2$, information about its stoichiometric use is generally unavailable in the literature. Because of the rarity and limited availability of CO$_2$ isotopomers, this parameter is of concern for applications in carbon-isotope labeling. We investigated the effects of the stoichiometry of labeled CO$_2$ on carbon isotope exchange of phenyl­acetic acids. Both thermal and photocatalytic procedures were studied, providing insight into product outcome and isotope incorporation. Preliminary results on isotope-dilution effects of carbonate bases in photocatalytic carboxylation reactions have also been obtained

A Sydnone-Based Route to Indazolo[2,3-a]quinoxaline Derivatives

International audienceAbstract A new synthetic route to indazolo[2,3-a]quinoxaline derivatives is described. The strategy is based on the 1,3-dipolar cycloaddition of arynes to quinoxaline–sydnone derivatives as a key step. The polyaromatic sydnones were prepared through a copper-promoted intramolecular cyclization of the C-4 position of sydnones on imines

Catalytic methoxylation of aryl halides using 13^{13}C- and 14^{14}C-labeled CO2_2

International audienceThe functionalization of carbon dioxide (CO$_2$) into high-value building blocks is a relevant topic in carbon isotope labeling, where CO$_2$ is the primary carbon source. A catalytic methoxylation of aryl halides directly from [$^{13}$C] and [$^{14}$C]CO$_2$ is reported. Relying on the intermediacy of the methoxyborane BBN-OCH$_3$, as new secondary nucleophilic labeled source, this strategy allowed labeling of a series of substrates, including challenging pharmaceuticals containing tertiary alkyl amine substituents

Parallel Screening with 14 C‐Labeled Carbon Dioxide: De‐risking the Staudinger‐Aza‐Wittig Reaction**

International audienceAbstract Carbon isotope labeling is a useful technology for tracking the fate of organic compounds in the environment and in living organisms. In this context, the development of robust and general methodologies amenable to the direct functionalization of CO 2 remains a significant task. In this communication, a de‐risking approach was developed to evaluate the robustness of the Staudinger aza‐Wittig sequence for carbon isotope labeling. This technology is based on [ 14 C]CO 2 screening that allowed to investigate the tolerance of the procedure with most representative heterocycles and functional groups found in FDA approved drugs

A Platform for Multiple Isotope Labeling via Carbon-Sulfur Bond Exchange

Isotopes are at the foundation of applications in life science such as nuclear imaging and are essential tools for the determination of pharmacokinetic and dynamic profiles of new pharmaceuticals. However, the insertion of an isotope into an organic molecule remains challenging and current technologies are element-specific. Despite the ubiquitous presence of sulfur in many biologically active molecules, sulfur isotope labeling is an underexplored field and sulfur isotope exchange has been overlooked. In this work, we explore a nickel-catalyzed reversible carbon-sulfur (C-S) bond activation strategy to achieve selective sulfur isotope exchange. This approach enables to move beyond standardized element-specific procedures and was applied to multiple isotopes, including deuterium, carbon-13, sulfur-34 and radioactive carbon-14. These results provide a unique platform for multiple isotope labeling and are compatible with a wide range of substrates, including pharmaceuticals. In addition, this technology proved its potential as isotopic encryption device of organic molecules

Sydnone‐Cyanines as Clickable Probes for Fluorescent Labelling

International audienceAbstract The synthesis of four clickable sydnone‐heptamethine cyanine derivatives is described in this article. The synthetic route is based on a palladium‐cross coupling reactions of sydnone boronates affording the desired sydnone‐cyanine conjugates in only five steps. These compounds were shown to react smoothly with cyclooctynes to form the corresponding pyrazoles clicked products quantitatively at room temperature and with rate constants up to 18 m −1 ⋅ s −1 , affording interesting new tools for biorthogonal fluorescent labelling of (bio)molecules. Fluorescence properties of both sydnone‐ and pyrazole‐cyanines are described, as well

Detection of expanded‐spectrum cephalosporin hydrolysis by lateral flow immunoassay

International audienceSummary Early detection of expanded‐spectrum cephalosporin (ESC) resistance is essential not only for an effective therapy but also for the prompt implementation of infection control measures to prevent dissemination in the hospital. We have developed and validated a lateral flow immunoassay (LFIA), called LFIA‐CTX test, for the detection of ESC (cefotaxime) hydrolytic activity based on structural discrimination between the intact antibiotic and its hydrolysed product. A single bacterial colony was suspended in an extraction buffer containing cefotaxime. After a 30‐min incubation, the solution is loaded on the LFIA for reading within 10 min. A total of 348 well‐characterized Gram‐negative isolates were tested. Among them, the 38 isolates that did not express any cefotaxime‐hydrolysing β‐lactamase gave negative results. Of the 310 isolates expressing at least one cefotaxime‐hydrolysing β‐lactamase, all were tested positive, except three OXA‐48‐like producers, which were repeatedly detected negative. Therefore, the sensitivity was 99.1% and the specificity was 100%. The LFIA‐CTX test is efficient, fast, low‐cost and easy to implement in the workflow of a routine microbiology laboratory