Robby Vroemans

Molecules, Vol. 26, Pages 5869: Searching Anti-Zika Virus Activity in 1H-1,2,3-Triazole Based Compounds

Molecules doi: 10.3390/molecules26195869

Authors: Willyenne M. Dantas Valentina N. M. de Oliveira Diogo A. L. Santos Gustavo Seabra Prem P. Sharma Brijesh Rathi Lindomar J. Pena Ronaldo N. de Oliveira

Zika virus (ZIKV) is a mosquito-borne virus belonging to the Flaviviridae family and is responsible for an exanthematous disease and severe neurological manifestations, such as microcephaly and Guillain-Barré syndrome. ZIKV has a single strand positive-sense RNA genome that is translated into structural and non-structural (NS) proteins. Although it has become endemic in most parts of the tropical world, Zika still does not have a specific treatment. Thus, in this work we evaluate the cytotoxicity and antiviral activities of 14 hybrid compounds formed by 1H-1,2,3-triazole, naphthoquinone and phthalimide groups. Most compounds showed low cytotoxicity to epithelial cells, specially the 3b compound. After screening with all compounds, 4b was the most active against ZIKV in the post-infection test, obtaining a 50% inhibition concentration (IC50) of 146.0 µM and SI of 2.3. There were no significant results for the pre-treatment test. According to the molecular docking compound, 4b was suggested with significant binding affinity for the NS5 RdRp protein target, which was further corroborated by molecular dynamic simulation studies.

Catalytic C(sp³)−H functionalization of alkanes and cycloalkanes is a useful tool to convert abundant chemical feedstocks into value-added products but remains a challenging task. In this review, recent advances relying on dual photo-induced hydrogen atom transfer and transition metal catalysis are summarized.

Abstract

Catalytic C(sp³)−H functionalization can convert abundant feedstock hydrocarbons into value-added products in an atom- and step-economic manner and is a powerful tool in organic synthesis. However, the intrinsic chemical inertness of ubiquitous aliphatic C−H bonds of alkanes and cycloalkanes makes their direct and selective functionalization extremely challenging. Recently, some elegant strategies have been developed to solve the problems based on the merger of photocatalyzed hydrogen atom transfer (HAT) with transition metal catalysis. Light-induced HAT processes are employed to initiate the alkyl radical generation, which is synergistic with metal catalysis involving for example nickel, copper, cobalt, cerium, chromium, or manganese. The different metal catalysts provide redox adjustment, Lewis acid activation or other functionalities and tune the reactivity and selectivity of the radical-mediated sequences, allowing the development of diverse chemo-, site-, and/or stereoselective synthetic reactions. In this minireview, we offer a brief summary of the recent advances in dual photo-induced HAT and transition metal catalysis for C−H functionalization of alkanes and cycloalkanes. We expect that these methodologies will stimulate the applications in catalysis, pharmaceuticals, and other related fields.

Publication date: 5 November 2021

Source: Tetrahedron, Volume 100

Author(s): Jie Feng, Ding Du

Nature Communications, Published online: 24 September 2021; doi:10.1038/s41467-021-25932-6

Nature Chemistry, Published online: 23 September 2021; doi:10.1038/s41557-021-00783-2

Publication date: 22 October 2021

Source: Tetrahedron, Volume 99

Author(s): Keying Ding

Publication date: 15 December 2021

Source: Coordination Chemistry Reviews, Volume 449

Author(s): Praveen Kumar Singh, Poulomi Majumdar, Surya Prakash Singh

Molecules, Vol. 26, Pages 5667: Synthesis of Biologically Relevant 1,2,3- and 1,3,4-Triazoles: From Classical Pathway to Green Chemistry

Molecules doi: 10.3390/molecules26185667

Authors: Lori Gonnet Michel Baron Michel Baltas

Green Chemistry has become in the last two decades an increasing part of research interest. Nonconventional «green» sources for chemical reactions include micro-wave, mechanical mixing, visible light and ultrasound. 1,2,3-triazoles have important applications in pharmaceutical chemistry while their 1,2,4 counterparts are developed to a lesser extent. In the review presented here we will focus on synthesis of 1,2,3 and 1,2,4-triazole systems by means of classical and « green chemistry » conditions involving ultrasound chemistry and mechanochemistry. The focus will be on compounds/scaffolds that possess biological/pharmacophoric properties. Finally, we will also present the formal cycloreversion of 1,2,3-triazole compounds under mechanical forces and its potential use in biological systems.

The first molybdenum-catalyzed C-alkylation between alcohols via borrowing hydrogen is reported.

Abstract

The first implementation of a molybdenum complex with an easily accessible bis-N-heterocyclic carbene ligand to catalyze β-alkylation of secondary alcohols via borrowing-hydrogen (BH) strategy using alcohols as alkylating agents is reported. Remarkably high activity, excellent selectivity, and broad substrate scope compatibility with advantages of catalyst usage low to 0.5 mol%, a catalytic amount of NaOH as the base, and H₂O as the by-product are demonstrated in this green and step-economical protocol. Mechanistic studies indicate a plausible outer-sphere mechanism in which the alcohol dehydrogenation is the rate-determining step.

Publication date: 8 October 2021

Source: Tetrahedron, Volume 98

Author(s): Daler Baidilov, Davit Hayrapetyan, Andrey Y. Khalimon

Next-generation, base-activated latent sulfinate reagents have been successfully developed for use in the construction of heteroaromatic frameworks, such as 2-arylpyridines. Under Pd-catalyzed conditions, these species unmask to give the sulfinate in situ, which then undergoes efficient desulfinative cross-coupling with an array of (hetero)aryl halides.

Abstract

Heteroaromatic sulfinates are effective nucleophilic reagents in Pd⁰-catalyzed cross-coupling reactions with aryl halides. However, metal sulfinate salts can be challenging to purify, solubilize in reaction media, and are not tolerant to multi-step transformations. Here we introduce base-activated, latent sulfinate reagents: β-nitrile and β-ester sulfones. We show that under the cross-coupling conditions, these species generate the sulfinate salt in situ, which then undergo efficient palladium-catalyzed desulfinative cross-coupling with (hetero)aryl bromides to deliver a broad range of biaryls. These latent sulfinate reagents have proven to be stable through multi-step substrate elaboration, and amenable to scale-up.

Nature, Published online: 06 September 2021; doi:10.1038/d41586-021-02428-3

Abstract

A metal-free protocol for the direct bis-arylation of 2,5-dichlorobenzoquinone with aryldiazonium salts is reported. The reactive salts are generated in situ and converted to radicals through irradiation with visible light. Reaction products precipitate from the solvent, eliminating the need for purification and thus providing a novel green method for the synthesis of versatile bis-electrophiles.

Beilstein J. Org. Chem. 2021, 17, 2315–2320. doi:10.3762/bjoc.17.149

Nature, Published online: 06 September 2021; doi:10.1038/d41586-021-02429-2

Hexaarylbenzene scaffolds , containing six different aromatic rings around the central benzene core, are a synthetic challenge. In their Research Article on page 22307, Svetlana B. Tsogoeva et al. report a process that allows the simple and straightforward generation of such hexaarylbenzenes (HABs). In an efficient, two-component four-step domino reaction, a functionalized triarylbenzene is formed and used as a key intermediate to furnish asymmetrically substituted HABs in high overall yield and without involvement of statistical steps.

A simple and efficient decatungstate catalyzed photochemical addition of 9-substituted fluorenyl radicals leads to the regioselective preparation of C₆₀-fluorene dyads in good yields. The cleavage of the C−H or C−D bond in 9-position of fluorene is the rate-determining step of the reaction, as indicated by KIE measurements.

Abstract

An innovative, efficient, regioselective functionalization of C₆₀ with 9H-fluorenes has been disclosed. This efficient photochemical approach uses certain fluorenyl radicals in 9-position deriving from fluorenes through a hydrogen-atom transfer (HAT) process mediated by tetrabutylammoniumdecatungstate [(n-Bu₄N)₄W₁₀O₃₂]. The single addition of these fluorenyl radicals to C₆₀ proceeded to produce [60]fullerene-fluorene dyads in a single step. The scope and mechanism of this new reaction have been examined. The primary kinetic isotope effect measurements signify the presence of a stepwise mechanism in which the C−H (D) bond scission is the rate-limiting step of the reaction.