This work was supported by the Foundation for Science and Technology (FCT), Portugal (projects PTDC/QUI-QUI/113687/2009 and PEst-C/QUI/UI0081/2013). A.G. (SFRH/BD/43531/2008) and M.J.M. (SFRH/BD/61262/2009) thank FCT for grants.

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Chromone: A Valid Scaffold in Medicinal Chemistry

Chromones as a privileged scaffold in drug discovery: a review.

An environmentally friendly electrocatalytic protocol has been developed for dehydrogenative C−H/S−H cross-coupling. This method enabled C−S bond formation under catalyst- and oxidant-free conditions. Under undivided electrolysis conditions, various aryl/heteroaryl thiols and electron-rich arenes afforded the C−S bond-formation products in 24–99 % yield. A preliminary mechanistic study indicated that the generation of aryl radical cation intermediates is key to the success of this transformation.

Electrocatalytic Oxidant‐Free Dehydrogenative C−H/S−H Cross‐Coupling

http://www.cs.gordon.edu/~ijl/_lead_papers/Natural%20and%20synthetic%2020-hydroxy-chalcones%20and%20aurones.pdf

Natural and synthetic 2'-hydroxy-chalcones and aurones: synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity.

We report the synthesis of a series of aryl- or alkyl-substituted 2-mercaptobenzothiazoles by direct thiolation of benzothiazoles with aryl or alkyl thiols via copper-mediated aerobic C-H bond activation in the presence of stoichiometric CuI, 2,2'-bipyridine and Na(2)CO(3). We also show that the approach can be extended to thiazole, benzimidazole, and indole substrates. In addition, we present detailed mechanistic investigations on the Cu(I)-mediated direct thiolation reactions. Both computational studies and experimental results reveal that the copper-thiolate complex [(L)Cu(SR)] (L: nitrogen-based bidentate ligand such as 2,2'-bipyridine; R: aryl or alkyl group) is the first reactive intermediate responsible for the observed organic transformation. Furthermore, our computational studies suggest a stepwise reaction mechanism based on a hydrogen atom abstraction pathway, which is more energetically feasible than many other possible pathways including β-hydride elimination, single electron transfer, hydrogen atom transfer, oxidative addition/reductive elimination, and σ-bond metathesis.

Copper-mediated C-H activation/C-S cross-coupling of heterocycles with thiols

Synthesis and antitumor activity of novel dithiocarbamate substituted chromones.

Microwave-assisted, one-pot syntheses and fungicidal activity of polyfluorinated 2-benzylthiobenzothiazoles.

1-Acetyl-3,-5-diarylpyrazolines have received considerable interests from the fields of medicinal and agricultural chemistry due to their broad spectrum of biological activities. To discover new lead compounds exhibiting both fungicidal and insecticidal activities, a series of pyrazoline derivatives were designed and synthesized by introducing the β-methoxyacrylate pharmacophore into the scaffold of 1-acetyl-3,5-diarylpyrazoline. The fungicidal activities against Pseudoperoniospora cubensis, Sphaerotheca fuliginea, Botrytis cinerea, and Rhizoctonia solani and the insecticidal activities against Aphis medicagini, Nilaparvata legen, Mythima separata, and Tetranychus cinnabarnus were screened. The most potent compound 13, 1-aceto-3-{m-[o-(E-1-methoxycarboxyl-2-methoxy)-1-yl]benzyloxy}phenyl-5-(benzo-[1,3]-dioxolyl)-4,5-dihydro- pyrazoline, was identified. Its fungicidal IC50 values against P. cubensis and S. fuliginea are 26.6 and 57.6 μg mL−1, respectively, while its insecticidal LC50 value against M. separ...

Synthesis, Fungicidal, and Insecticidal Activities of β-Methoxyacrylate-Containing N-Acetyl Pyrazoline Derivatives

Design, syntheses, and antitumor activity of novel chromone and aurone derivatives.

Strobilurin derivatives have become one of the most important classes of agricultural fungicide due to a novel action mode, wide fungicidal spectrum, lower toxicity toward mammalian cells, and environmentally benign characteristics. To discover new strobilurin analogues with high activity against resistant pathogens, a series of new chalcone-based strobilurin derivatives are designed and synthesized by integrating a chalcone scaffold with a strobilurin pharmacophore. The preliminary bioassay showed that some of the chalcone analogues exhibited good in vivo fungicidal activities against Pseudoperoniospora cubensis and Sphaerotheca fuliginea at the dosage of 200 microg mL(-1). Two compounds, (E)-methyl 2-[2-({3-[(E)-3-(2-chlorophenyl)acryloyl]phenoxy}methyl)phenyl]-3-methoxyacrylate (1e) and (E)-methyl 2-[2-({3-[(E)-3-(3-bromophenyl)acryloyl]phenoxy}methyl)phenyl]-3-methoxyacrylate (1l), were found to display higher fungicidal activities against P. cubensis (EC90=118.52 microg mL(-1) for 1e and EC90=113.64 microg mL(-1) for 1l) than Kresoxim-methyl (EC90=154.92 microg mL(-1)) and were identified as the most promising candidates for further study. The present work demonstrated that strobilurin analogues containing chalcone as a side chain could be used as a lead structure for further developing novel fungicides. To our knowledge, this is the first report about the syntheses and fungicidal activities of chalcone-based strobilurin derivatives.

Wei Huang

Papers

Synthesis and antitumor activity of novel dithiocarbamate substituted chromones.

Microwave-assisted, one-pot syntheses and fungicidal activity of polyfluorinated 2-benzylthiobenzothiazoles.

Synthesis, Fungicidal, and Insecticidal Activities of β-Methoxyacrylate-Containing N-Acetyl Pyrazoline Derivatives

Design, syntheses, and antitumor activity of novel chromone and aurone derivatives.

Synthesis and fungicidal evaluation of novel chalcone-based strobilurin analogues