The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry and the construction of 2 electronic devices. This review discusses the mechanism, scope and applications of the RuAAC reaction, covering the literature during the last 10 years.
CONTENTS
Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.
An experimentally simple sequential one-pot RuAAC reaction, affording 1,5-disubstituted 1H-1,2,3-triazoles in good to excellent yields starting from an alkyl halide, sodium azide, and an alkyne, is reported. The organic azide is formed in situ by treating the primary alkyl halide with sodium azide in DMA under microwave heating. Subsequent addition of [RuClCp*(PPh(3))(2)] and the alkyne yielded the desired cycloaddition product after further microwave irradiation.
The synthesis of P-N-P bidentate ligands and the evaluation, based on IR and X-ray data, of their pi-acceptor properties in the complexes derived from phenylacetylene-dicobalt hexacarbonyl have been carried out. In addition, the reactivity of these complexes in the Pauson-Khand reaction has been examined.
Recent developments concerning the application of polymer supported organometallic reagents in solid phase synthesis are reviewed, with a special focus on methodology for carbon-carbon formation. Examples of reactions that are covered include the classical Suzuki, Sonogashira and Heck coupings, but also aryl amination, epoxide opening, rearrangements, metathesis and cyclopropanation. Applications in the field of asymmetric synthesis are also discussed.
Molecular solar-thermal energy storage (MOST) systems are based on photoswitches that reversibly convert solar energy into chemical energy. In this context, bicyclooctadienes (BOD) undergo a photoinduced transformation to the corresponding...
Non‐natural peptides with structures and functions similar to natural peptides have emerged lately in biomedical as well as nanotechnological contexts. They are interesting for pharmaceutical applications since they can adopt structures with new targeting potentials and because they are generally not prone to degradation by proteases. We report here a new set of peptidomimetics derived from δ‐peptides, consisting of n units of a 1,5‐disubstituted 1,2,3‐triazole amino acid (5Tzl). The monomer was prepared using ruthenium‐catalyzed azide–alkyne cycloaddition (RuAAC) chemistry using [RuCl2Cp*]x as the catalyst, allowing for simpler purification and resulting in excellent yields. This achiral monomer was used to prepare peptide oligomers that are water soluble independent of peptide chain length. Conformational analysis and structural investigations of the oligomers were performed by 2D NOESY NMR experiments, and by quantum chemical calculations using the ωB97X‐D functional. These data indicate that several conformations may co‐exist with slight energetic differences. Together with their increased hydrophilicity, this feature of homo‐5Tzl may prove essential for mimicking natural peptides composed of α‐amino acids, where the various secondary structures are achieved by side chain effects and not by the rigidity of the peptide backbone. The improved synthetic method allows for facile variation of the 5Tzl amino acid side chains, further increasing the versatility of these compounds.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.