Current Organic Synthesis - Volume 20, Issue 3, 2023

Cu-catalyzed carbon-heteroatom bond formation is a powerful tool in the field of organic synthesis. In the past two decades, numerous Cu-based catalytic systems are developed in both homogeneous and heterogeneous forms. Important developmentshave been reported on Cubased catalytic systems in the field of C-Chalcogenide cross-coupling in the last few decades. Where homogeneous Cu/L-based catalytic systems are found to perform reactions with high selectivity, heterogeneous supported-Cu and Cu-based nanoparticles are found to perform the reactions under sustainable conditions and high recyclability of catalytic systems. This present overview mainly focuses on the recent advances and applications in this fast-growing research field with an emphasis on copper-catalyzed cross-coupling generations of carbon-chalcogenide (S/Se/Te) bonds.

Background: 2-Hydroxy-1,4-Naphthoquinone (HNQ; Lawsone) is one of the most useful and the simplest naturally occurring naphthoquinones and has stimulated a resurgence of interest in the past decades due to a wide range of pharmacological activities. Introduction and Methods: This activity has led to the unusually large emphasis being placed on the design of more efficient multi-component reactions (MCRs) in the synthesis of bioactive lawsone derivatives. Results and Conclusion: This review highlights the recent developments in multi-component synthesis of biologically relevant naphthoquinone linked and fused heterocyclic derivatives carried out from 2015 till now.

Palladium-catalyzed organic reactions are ubiquitous due to their high efficiency in coupling reactions and have wide applications in synthetic chemistry. Their widespread use in organic synthesis has been attributed to moderate conditions associated with reactions and tolerance to different types of functional groups. Palladium-catalysts are extensively used in aminocarbonylation of aryl halides for the synthesis of amides and have found a wide variety of applications in pharmaceuticals, agrochemicals, petrochemicals, materials, polymers, etc. In this review, we summarize the recent advances in the synthesis of amides via palladium-catalyzed aminocarbonylation of aryl halides, and cover literature from 2010 to 2021.

Background: Literature survey suggested various methods of synthesis of the 3- azabicyclo [3.3.1] nonanes which include, Mannich reaction, α, α'-Annelation of Cyclic Ketones or through Enamines, Michael addition, Intramolecular Cyclizations, etc. However, a mechanism following a Michael addition path through the formation of the dibenzylidene cyclohexanone intermediate can not be ignored. Thus to ensure the mechanistic pathway for the formation of 2,4-diphenyl- 3-azabicyclo[3.3.1]nonan-9-one and to understand the reactivity of a conformationally and biologically important molecule for the synthesis of spiro-s-tetrazine derivatives and its further functionalization with thiazole and thiazolidinone derivatives the present work has been undertaken. Methods: Direct reaction of dibenzylidene cyclohexanone and ammonium acetate has been tried to get the confirmation of Mannich/ Michael reaction pathway for the formation of 2,4-diphenyl-3- azabicyclo[3.3.1]nonan-9-one. Synthesis of the spiro-s-tetrazine derivative has been accomplished by the simple condensation reaction of azabicyclic system and thiocarbohydrazide (TCH). Simple methods have been adopted for the installation of heterocyclic moieties like thiazolidinone, thiazole. Results: Failure of the attempts to prepare 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-onedirectly from dibenzylidene cyclohexanone ruins the possibility of Michael addition reaction and supports the formation of the product through Mannich reaction. Synthesis of the spiro derivatives containing tetrazine, thiazole, thiazolidinone moieties were achieved by using simple techniques and products were obtained in good yield. FTIR, NMR spectroscopy are used for the characterization of all the molecules. Formation of 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-onewas confirmed by using some additional data like mass and single crystal XRD. Conclusion: Confirmation of the mechanistic route for the 2 2,4-diphenyl-3- azabicyclo[3.3.1]nonan-9-one was achieved and simple methods for the formation of spiro derivatives containing tetrazine, thiazole, thiazolidinone were established.

Background: The studies on the potential usage of benzene sulfonamide derivatives as anticancer agents are limited. benzene sulfonamide derivatives are currently used as anticancer agents against different breast cancer cell lines, such as MCF-7, lung cancer cells (A549), prostate cancer cells (Du-145), and cervical cells (HeLa). Objective: A series of new sulfonamide drugs are synthesized by reacting aldehydes thio-semi-carbazones derivatives with benzene sulphonyl chloride to form benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide derivatives. Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. Methods: Studying the anticancer effects against MCF-7 breast carcinoma cell lines and the antioxidant activities of these newly synthesized compounds. To study the anti-breast cancer activity of the newly synthesized compounds, a molecular docking study is used to analyze the binding energy for the nonbonding interactions between the ligands (studied compounds) and receptor (4PYP (pdb code: 4FA2)) against human breast cancer (MCF-7) cells. The bioavailability of all studied compounds is confirmed by pharmacological investigations using Mol inspiration and absorption, distribution, metabolism, excretion, and toxicity online servers. Results: The two derivatives, 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4c) and 2-(4-dimethylamino) benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4e) show the most potent anticancer effects against MCF-7 breast carcinoma cell lines. Meanwhile, these two derivatives show the lowest antioxidant activities. Conclusion: The different spectral techniques were used to confirm the structure of the novel synthesized compounds. Further, 2-(4-(dimethyl amino) benzylidene)-N- (phenylsulfonyl)hydrazine-1-carbothioamide (4e) and 2-(4- methoxy benzylidene)-N-(phenylsulfonyl) hydrazine-1 carbothioamide (4c) were the most potent anticancer derivatives against MCF-7 breast carcinoma cell lines. Furthermore, they exhibited the most potent antioxidant activities. Meanwhile, the 2-benzylidene-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4a) and 2-(4-chloro benzylidene)-N-(phenylsulfonyl) hydrazine-1-carbothioamide (4d) had the lowest antioxidant potentials. The estimated binding energies, inhibition constant, intermolecular energies, and reference RMSD produced from docking for all studied compounds were reported. These values showed that all studied compounds formed stable complexes with the receptor with high binding affinity. It was further noted from the ADMET analysis that compounds 4c, 4d, and 4e have good absorption, low toxicity in the human liver, and medium BBB penetration. Hence, these studied compounds (4c-4e) may be suggested as potential compounds against human breast cancer MCF-7 cells.

Background: Plant diseases caused by viruses and pathogens have posed a serious threat to global agricultural production and are difficult to control. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. The natural product resveratrol was found to have good antiviral activity against the tobacco mosaic virus (TMV) and fungicidal activities against 14 kinds of phytopathogenic fungi. Objective: The aim of this work was to design, synthesize a series of derivatives of resveratrol, and evaluate their antiviral and fungicidal activities systematically. Methods: Novel resveratrol sulfonate derivatives were prepared by a convenient synthesis method from resveratrol, alkyl sulfonyl chloride, aryl sulfonyl chloride, and heterocyclic sulfonyl chloride. Their structures were also identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). Results: Most of the targets were obtained at a high yield. Compounds I-2, I-5, I-10, II-2, and II-4, with excellent antiviral activities, showed higher anti-TMV activities than those of lead compounds and commercial ribavirin (inhibitory rates of 38, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively). In particular, compounds I-5, I-10, II-2, and II-4 displayed similar inhibitory effects as ningnanmycin (inhibitory rates of 54, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best antiviral agent at present, thereby emerging as new antiviral pilot compounds. Further fungicidal activity tests showed that resveratrol derivatives also displayed broad-spectrum fungicidal activities. Conclusion: The anti-TMV activities of these compounds were discovered for the first time. Some of these simply structured compounds showed higher TMV inhibitory effects than ribavirin. The current study provided valuable insights into the antiviral and fungicidal activities of resveratrol derivatives, but more modification of the structure should be conducted.