Eosin Y-catalyzed synthesis of oxazole via intermolecular CN and CO bond formation.
An efficient visible light-mediated, eosin Y-catalyzed synthesis of oxazole has been developed from benzil with primary amines, that providing a straightforward, green, and environmentally benign access to a wide variety of substituted oxazole-2-amines under mild reaction conditions.
An efficient method for the synthesis Quinoline, Pyridine and pyrrole has been achieved by a new catalytic synstem. The control experiments suggested these reactions were performed through Dehydrogenation reaction.
The role of new series of phosphine-free aurone ligands have been investigated in microwave-enhanced Mn (II) and Co (II) dehydrogenative coupling reactions. Various heterocyclic compounds such as Quinoline, pyridine, and pyrrole have been synthesized and characterized by NMR spectroscopy. The synthesized ligands (L1–L4) with Mn(II) and Co (II) salt showed excellent catalytic activity and proved to be very effective for the dehydrogenative coupling reaction. This synthetic method involves the in-situ formation of a metal ligand complex that was analyzed by mass spectrometry. A broad range of substrates including aliphatic ketone, heterocycles, and sterically hindered Ketone coupling partners are well tolerated in the developed protocol.
The present work emphasizes catalyst-free imidazole synthesis using diversified aldehydes, benzil, ammonium acetate, or amines. Ammonium acetate as a reactant catalyst by dissociating into acetic acid for formation to ascertain the imidazoles. The advantages are efficient, greener, and with moderate to excellent yield in shorter reaction time in ethanol:water, a greener solvent.
The present work emphasizes catalyst-free 2,4,5-tri- and 1,2,4,5-tetra substituted imidazole synthesis using diversified aldehydes with benzil, ammonium acetate, or amines. Ammonium acetate plays a vital role as a reactant catalyst by dissociating into acetic acid to afford imine and diamine formation to ascertain the 2,4,5-tri- and 1,2,4,5-tetra substituted imidazoles. The key advantages of the current approach are efficient, greener, eco-friendly, and facile, with moderate to excellent yield in shorter reaction time at the temperature of 80°C. Ethanol:water as a solvent makes the reaction process eco-friendly. Overall, the described approach offers a promising route for the efficient and sustainable synthesis of substituted imidazoles, which have a wide range of applications in various fields, including pharmaceuticals, agrochemicals, and materials science.
![Cu-catalyzed dehydrogenative C<span class='icomoon'></span>O arylation for the synthesis of 6-methyl benzofuro[3,2-c] quinoline derivatives](https://onlinelibrary.wiley.com/cms/asset/fd580e7a-1d1f-4d1f-a1ec-7373199ea950/jhet4774-toc-0001-m.png)
Copper catalyzed dehydrogenative C—O arylation
A novel strategy for the synthesis of 6-methyl benzofuro[3,2-c] quinoline derivatives via copper-catalyzed dehydrogenative CO arylation has been presented. Optimization studies have been carried out by varying various catalysts, bases, solvents, and other physical parameters. Keeping use of this dehydrogenative cross-coupling CO arylation reaction, a variety of bioactive building blocks like fused benzofuro quinoline heterocycles were smoothly assembled in moderate to higher yields.
A series of novel thiazine derivatives featuring axial chirality in both (R) and (S) configurations were successfully synthesized by N-heterocyclic carbene-catalyzed enantioselective [3 + 3] annulations, and their potential as anti-plant virus agents against potato virus Y was evaluated.
A series of novel thiazine derivatives featuring axial chirality in both (R) and (S) configurations were successfully synthesized by N-heterocyclic carbene (NHC)-catalyzed enantioselective [3 + 3] annulations, and their potential as anti-plant virus agents against potato virus Y (PVY) was evaluated. Biological activity results demonstrated that most of these chiral thiazine derivatives exhibited significant activities against PVY. Notably, compound (S)-3g displayed a remarkable 58% inactivation effect against PVY at a concentration of 500 μg/mL, slightly surpassing the effectiveness of Ningnanmycin (NNM) at 57%. Additionally, (S)-3g exhibited curative activity of 57%, which is superior to NNM (53%). Molecular docking studies revealed preliminary insights into the distinct biological properties of the two different enantiomers, (R) or (S)-3g against PVY, wherein single enantiomer (S)-3g formed a more stable interaction with PVY-CP, as indicated by its lower binding free energy (−41.18 kcal/mol) compared to (R)-3g (−36.9 kcal/mol). The findings in this study with a new class of axially chiral thiazine derivatives shall inspire further development of chiral heterocycles as potential drug candidates for the protection of plant virus infections.
The results from this study demonstrate that the planarity in azoles does contribute toward insensitivity. The safety advantage of planar 1,3,4-oxadiazole-tetrazole mixed azole is combined with the energy of nitroamine to achieve better physiochemical properties.
Nitrogen-rich energetic materials based on five-membered azoles, such as tetrazoles, triazoles, oxadiazoles, pyrazoles, and imidazoles, have garnered significant attention in recent years due to their environmental compatibility while maintaining high performance. These materials, including explosives, propellants, and pyrotechnics, are designed to release energy rapidly and efficiently while minimizing the release of toxic or hazardous byproducts and have attracted potential applications in the defense and space industries. The presence of extensive NC, NN, and NN high energy bonds in azoles provides high enthalpies of formation and facilitates intermolecular interactions through π-stacking which may help with reducing sensitivity to external stimuli. Now, we report on the synthesis and energetic properties of N-(5-(1H-tetrazol-5-yl)-1,3,4-oxadiazol-2-yl)nitramide (5) and its energetic salts. These new high nitrogen–oxygen-containing materials have attractive feature applications of insensitivity and increased performance.
![Synthesis and antiviral activity of novel imidazo[2,1-b]thiazoles coupled with morpholine and thiomorpholines](https://onlinelibrary.wiley.com/cms/asset/e2cdd361-e415-40d8-acb6-6fc14cda7f51/jhet4778-toc-0001-m.png)
Synthesis and screening of morpholine and thiomorpholine coupled imidazo[2,1-b]thiazoles for their in vitro antiviral activity against influenza virus, resulted two analogs, 7d and 7e as most potent analogs with favorable toxicity profile.
Herein described the synthesis and antiviral evaluation of a novel series of morpholine and thio-morpholine coupled imidazo[2,1-b]thiazoles. The three-step reaction sequence involving the condensation of 1,3-dichloroacetone with thiourea followed by coupling with morpholine and thiomorpholine and finally cyclization with substituted α-bromoacetophenones yielded the desired imidazothiazoles 7(a–l). Screening of all the new compounds for their in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, resulted in two potent analogs, 7d (IC50: 1.1 μM, C50: >300 μM, SI = 273) and 7e (IC50: 2.0 μM, C50: >300 μM, SI = 150), with a favorable toxicity profile and are the best anti-influenza hit analogs for further structural optimization.
A novel series of L-carvone-derived pyrimidine-urea compounds with antiproliferative activity were designed and synthesized, along with the investigation for their structure-activity relationship.
To explore novel natural product-based nitrogen-containing heterocyclic compounds with antiproliferative activity, 20 L-carvone-derived pyrimidine-urea compounds 4a–4t were synthesized through the multi-step reaction of L-carvone, and structurally characterized by Fourier transform infrared (FT-IR), hydrogen-1 nuclear magnetic resonance (1H-NMR), Carbon-13 nuclear magnetic resonance (13C-NMR), and High-resolution mass spectrometry (HRMS). Besides, the in vitro antiproliferative activity of the target compounds against HepG2, Hela, and MCF-7 cells was evaluated by methyl thiazolyl tetrazolium (MTT) assay. According to the results, the target compounds showed certain inhibitory activities against the tested cancer cell lines, and five compounds (4b, 4h, 4k, 4l, and 4t) exhibited better inhibition activities against Hela cells than the positive control (5-FU). Among them, compound 4b held significant antiproliferative activities against Hela and HepG2 cells, and thus deserved further study as a leading compound of new anticancer drugs. In addition, an effective and reasonable three-dimensional quantitative structure-activity relationships (3D-QSAR) model was built by the Comparative molecular field analysis (CoMFA) method to analyze the relationship between the structures of the target compounds and their antiproliferative activities (expressed as pIC50) against Hela cells, and proven to have good predictive ability. Molecular docking was carried out to study the possible binding modes of compound 4b and Survivin, and it was found that compound 4b could be well embedded into the active site, along with the formation of several hydrogen bonds and hydrophobic interactions.
Novel pyrazole-biphenyl carboxamides showed dual antimicrobial and SARS-CoV2 entry-level inhibition activity potentials. The antimicrobial activity was broad-spectrum and the in-silico SARS-CoV2 spike protein, a main causative agent of COVID-19, was found to restrict its entry-level interaction with human Angiotensin Converting Enzyme (hACE). Thus, these novel molecules could have been the future drugs to treat both microbial and viral infections.
Microbial diseases including viral infection are big issues globally. Effective medicinal discovery for them is the need for the day. In this study, we report pyrazole-biphenyl-carboxamides (4a-l) validated for their SARS-CoV2 entry-level restriction effect over studying the protein–protein interaction of SARS-CoV2 with human ACE protein. Their extended antimicrobial properties were also evaluated. Online and offline software tools predicted MD simulation and ADMET druggability in silico. The antimicrobial efficacy of all compounds was also evaluated against Gram+ve Streptococcus pneumoniae (MTCC 1936), Staphylococcus aureus (MTCC 737) and Gram-ve Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424) (bacteria). In the results, compounds 4g and 4i were evenly active against both bacteria at a low concentration range (MIC: 1.00 to 9.5 μg/mL) and displayed lesser toxicity to tested mammalian cells (EC100 = 75 μg/mL). Furthermore, it was able to kill metabolically inactive bacterial cells and eradicate established biofilms of Methicillin-resistant Staphylococcus aureus (MRSA). Both the compounds inhibited DNA gyrase well with an IC50 0.25 μM (96% relative activity) and 0.52 μM (97% relative activity) respectively. Compounds (4a-l) showed restrictive efficiency of SARS-CoV2 spike protein (SC2SP) and human angiotensin-converting enzyme 2 (hACE2) entry-level association in COVID-19 in silico. To assess this ability, firstly, we identified the crucial amino acid residues involved in the interface of SARS-CoV-2 and hACE2 virtually. We recognized the ability of 4a-l binding to the binding interface to SARS-CoV2; thus, the interaction of SC2SP-hACE2 was effectively inhibited.
Sc(OTf)3-catalyzed tandem (3+3)-annulation/lactonization of cyclopropanes with salicylaldehyde nitrones to access polycyclic 1,2-oxazines with excellent diasteroselectivies.
A Sc(OTf)3-catalyzed tandem (3 + 3)-annulation/lactonization of donor-acceptor cyclopropane 1,1-dieters with salicylaldehyde nitrones has been reported, affording a wide range of tetrahydrochromeno[4,3-c][1,2]oxazin-5(1H)-ones in moderate yields with excellent diastereoselectivities. Besides, the gram-scale reaction has also been explored to demonstrate the utility of this protocol. Moreover, the mechanism was investigated through control experiments, which show the reaction proceeds via a tandem (3 + 3)-annulation/lactonization reaction.