Showing papers in "Helvetica Chimica Acta in 2019"
TL;DR: This work presents the optimization and validation procedures for three copper and palladium-catalyzed reactions (Suzuki cross-coupling, Sonogashira cross- coupling and copper(I)-catalyzing alkyne-azide cycloaddition) which have been successfully used by this group for the construction of large encoded libraries.
Abstract: The construction of DNA-encoded chemical libraries (DECLs) crucially relies on the availability of chemical reactions, which are DNA-compatible and which exhibit high conversion rates for a large number of diverse substrates. In this work, we present our optimization and validation procedures for three copper and palladium-catalyzed reactions (Suzuki cross-coupling, Sonogashira cross-coupling and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC)), which have been successfully used by our group for the construction of large encoded libraries.
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TL;DR: In this article, a cyclometallated iridium complex bearing a helicenic :C^C+ and two :N^C− dfppy (2−(2,4−difluorophenyl)‐pyridyl) ligands was prepared.
Abstract: A new enantiopure cyclometallated iridium complex bearing a [4]helicenic :C^C– and two :N^C– dfppy (2‐(2,4‐difluorophenyl)‐pyridyl) ligands was prepared. This complex revealed a long‐lived phosphorescence both in solution and in the solid state. Its chiroptical properties, namely electronic circular dichroism and circularly polarized luminescence, were also examined. Comparison with former chiral complexes enabled assignment of the Delta‐Ir‐(‐) and Lambda‐Ir‐(+) absolute configurations.
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TL;DR: The experiments show that chimera design represents a useful strategy to improve the properties of AMPDs and displays all previously observed activities while retaining a similar mechanism of action.
Abstract: We recently reported the discovery of antimicrobial peptide dendrimers (AMPDs) acting by a membrane‐disruptive mechanism against multidrug resistant pathogenic bacteria. Here, we combined amino acid sequence elements from different AMPDs with different activity profiles to form AMPD chimeras. By joining the outer branches of TNS18, an AMPD active against Pseudomonas aeruginosa, Acinetobacter baumannii and methicillin resistant Staphylococcus aureus, with the core of T7, another AMPD active against P. aeruginosa, A. baumannii and Klebsiella pneumoniae, we obtained AMPD chimera DC5 displaying all previously observed activities while retaining a similar mechanism of action. These experiments show that chimera design represents a useful strategy to improve the properties of AMPDs.
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TL;DR: The thiol‐mediated opening of 3‐alkyl‐1,2‐dithiolanes and diselenolanes is described, and the thiolate nucleophile is shown to react specifically with the secondary chalcogen atom, against steric demand, probably because the primary chalCogen atom provides a better leaving group.
Abstract: The thiol‐mediated opening of 3‐alkyl‐1,2‐dithiolanes and diselenolanes is described. The thiolate nucleophile is shown to react specifically with the secondary chalcogen atom, against steric demand, probably because the primary chalcogen atom provides a better leaving group. Once released, this primary chalcogen atom reacts with the obtained secondary dichalcogenide to produce the constitutional isomer. Thiolate migration to the primary dichalcogenide equilibrates within ca. 20 ms at room temperature at a 3 : 2 ratio in favor of the secondary dichalcogenide. The clarification of this focused question is important for the understanding of multifunctional poly(disulfide)s obtained by ring opening disulfide exchange polymerization of 3‐alkyl‐1,2‐dithiolanes, to rationalize the cellular uptake mediated by 3‐alkyl‐1,2‐diselenolanes as molecular walkers and, perhaps, also of the mode of action of pyruvate dehydrogenase complexes. The isolation of ring‐opened diselenolanes is particularly intriguing because dominant selenophilicity disfavors ring opening strongly.
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TL;DR: In this article, two ruthenium polypyridyl complexes were conjugated to vitamin B12 (Cobalamin, Cbl) to take advantage of the solubility and active uptake of the latter.
Abstract: The current photosensitizers (PSs) for photodynamic therapy (PDT) lack selectivity for cancer cells. To tackle this drawback, in view of selective cancer delivery, we envisioned conjugating two ruthenium polypyridyl complexes to vitamin B12 (Cobalamin, Cbl) to take advantage of the solubility and active uptake of the latter. Ultimately, our results showed that the transcobalamin pathway is unlikely involved for the delivery of these ruthenium-based PDT PSs, emphasizing the difficulty in successfully delivering metal complexes to cancer cells.
TL;DR: In this paper, a procedure for the iodoamination of unfunctionalized olefins tethered to a tosyl-protected NH-group has been developed, where the combined use of KI and H2O2 in aqueous medium was effective for the preparation of iodomethyl-substituted nitrogen-containing heterocycles.
Abstract: A procedure for the iodoamination of unfunctionalized olefins tethered to a tosyl-protected NH-group has been developed. The combined use of KI and H2O2 in aqueous medium was effective for the preparation of iodomethyl-substituted nitrogen-containing heterocycles. The selective exo-trig iodocyclization provided 1,2-bifunctional 5-, 6-, and 7-membered cyclic skeletons.
TL;DR: In this article, the aromatic core of an overcrowded alkene-based molecular motor is extended with the goal of inducing isomerization with visible light instead of harmful UV light.
Abstract: The aromatic core of an overcrowded alkene-based molecular motor is extended with the goal of inducing isomerization with visible light instead of harmful UV light. In our design, the common naphthalene moiety in the upper half of the motor is changed to pyrene. The photochemical and thermal isomerization processes are studied in detail using DFT calculations as well as NMR and UV/VIS spectroscopy. Our studies confirm that extension of the pi-system of the upper half successfully leads to a shift of the excitation wavelength into the visible region, while retaining proper rotary function.
TL;DR: In this article, the authors used triethylsilane as the silylating reagent in the presence of potassium tert-butoxide (KH) to silylate primary and secondary amines.
Abstract: Silylation of primary and secondary amines is reported, using triethylsilane as the silylating reagent in the presence of potassium tert-butoxide (KOtBu). The reaction proceeds well in the presence of 0.2 equiv of KOtBu. In competition experiments, aniline is selectively silylated over aliphatic amines. Computational studies support a catalytic mechanism which is initiated by KOtBu interacting with the silane to form KH and silylated amine. The KH then takes over the role of base in the propagation of the cyclic mechanism, and deprotonates the amine. This reacts with R3SiH to afford the product R3SiNR’R” and regenerate KH.
TL;DR: Interestingly, it is not only the initial ring‐opening but also the latter reversible Mannich reaction of the imino‐substituted ethano Troger base intermediate that is responsible for the loss of enantiospecificity.
Abstract: Polycyclic indoline‐benzodiazepines are afforded in one step by the reaction of Troger bases with N‐sulfonyl‐1,2,3‐triazoles under Rh(II) catalysis. After α‐imino carbene formation, the process involves a cascade of [1,2]‐Stevens rearrangement, Friedel‐Crafts, Grob fragmentation, and aminal formation reactions. It is highly diastereoselective (d.r. >49:1, four stereocenters incl. two bridgehead N‐atoms). However and in contrast with other reported carbene additions to these moieties, full racemization occurs when enantiopure Troger bases are used as substrates. To pinpoint the origin of this unexpected behavior, a key elemental step of the mechanism was evaluated and tested. Interestingly, it is not only the initial ring‐opening but also the latter reversible Mannich reaction of the imino‐substituted ethano Troger base intermediate that is responsible for the loss of enantiospecificity.
TL;DR: A robust and general protocol for a sustainable copper-free Sonogashira cross coupling under micellar aqueous reaction conditions with high turnover was developed, giving access to alkynylated arenes, heterocyclic compounds and monofunctionalized products from dihalogenated substrates with an improved selectivity achieved by the micellAR aqueously reaction conditions.
Abstract: A robust and general protocol for a sustainable copper-free Sonogashira cross coupling under micellar aqueous reaction conditions with high turnover was developed. By using the commercially available catalyst CataCXium A Pd G3 and THF as co-solvent, various alkyne substrates were efficiently cross-coupled with a broad range of aryl halides, providing improved yields and low catalyst loadings. The reaction parameters were optimized to render the process operationally simple, robust and scalable. The method gives access to alkynylated arenes, heterocyclic compounds and monofunctionalized products from dihalogenated substrates with an improved selectivity achieved by the micellar aqueous reaction conditions.
TL;DR: The tetravalent ligand was found to bind LecA in the nanomolar range involving all of its sugar (sub)ligands and was a considerably better biofilm inhibitor with half inhibitory values around the 28 micromolar range.
Abstract: A potent divalent ligand of the Pseudomonas aeruginosa adhesion lectin LecA was elaborated into a tetravalent version. A polyethylene glycol (PEG) spacer was introduced to link two divalent galactosides. Each of the two divalent ligands contained a rigid spacer with a central phenyl group that is bridged by the PEG moiety. The resulting tetravalent ligand was found to bind LecA in the nanomolar range involving all of its sugar (sub)ligands. Analytical ultracentrifugation studies clearly showed that the tetravalent ligand was capable of aggregation the LecA tetramers in contrast to the divalent ligands. The aggregator behavior was found to be of importance in P. aeruginosa biofilm formation inhibition. Despite the weaker affinity it was a considerably better biofilm inhibitor with half inhibitory values around the 28 micromolar range.