Search Results (194)

This work presents a revised total synthesis of two pharmacologically relevant benzofurans using newly developed environmentally friendly methodologies. In particular, we focused on establishing improved synthetic routes to stilbene dimers under milder and more sustainable reaction conditions. During our investigations, we optimized an efficient Sonogashira coupling carried out in water, which, followed by a Suzuki-like reaction conducted in dimethyl carbonate (DMC) in the absence of any transition metals, served as the key step for the synthesis of the benzofuran core. Full article

The epidermal growth factor receptor (EGFR) is a highly attractive and promising target for novel anticancer agents, particularly for non-small-cell lung cancer (NSCLC), due to its crucial role in regulating cell survival and proliferation. Despite the development of first-generation reversible inhibitors like Gefitinib and Erlotinib, acquired resistance necessitated the discovery of highly potent irreversible inhibitors effective against drug-resistant mutants. Molecular docking calculations utilizing both EGFR conformations identified five top-ranked compounds (QN012, QN017, QN019, QN022, and QN023) proposed for synthesis and biological evaluation. These in silico studies predicted high inhibitory activity against the active and inactive state of EGFR. Herein, we report the design, synthesis and biological evaluation of novel 4-anilino quinazoline derivatives, bearing various alkynyl substituents at position 6, expected to bind to the hinge Met793 residue of EGFR. The effects of the derivatives on various cancer cell lines in terms of cytotoxic/cytostatic activity, interference with cell cycle phase distribution, and suppression of EGFR phosphorylation set the basis for the design of more potent derivatives. Full article

A novel 3,6-dicarbonyl-substituted derivative of 2-chloropyrazine has been synthesized for the first time via regioselective dilithiation using lithium 2,2,6,6-tetramethylpiperidide (LiTMP) and subsequent trapping with methyl benzoate. The structure was unambiguously confirmed through Sonogashira coupling and diagnostic NMR analysis, establishing selective substitution at both the 3- and 6-positions. This result demonstrates that symmetrical 3,6-functionalization of 2-chloropyrazine is feasible under mild conditions, overcoming long-standing limitations of multiple metalations in electron-deficient heterocycles and opening new pathways for the synthesis of polyfunctional pyrazine frameworks. Full article

This work describes the straightforward synthesis of a novel heterogeneous palladium catalyst immobilized on magnetic Janus-type silica particles coated with an amphiphilic ionic liquid (IL) layer. The material was prepared via a one-pot process wherein TEOS (tetraethoxysilane) and a bis(triethoxysilane) IL precursor are combined to form hollow shells. The IL motifs are selectively located on the outer surface of the hollow particles and serve as centers for the immobilization of palladium species on the material’s surface. The outer surface also hosts magnetic nanoparticles in close proximity to the palladium sites. Thanks to the uniform coverage of the surface with the amphiphilic IL functionality, the material exhibits a well-balanced wettability with reaction components of different polarities. The catalyst’s activity was tested in the Sonogashira cross-coupling reaction of terminal acetylenes and iodobenzene derivatives in water as the solvent. The results show that the mixed palladium–iron oxide catalyst exhibits higher activity than materials containing either immobilized palladium or iron oxide alone, suggesting a synergistic effect in this reaction. Additionally, the reaction proceeds well in the absence of expensive organic ligands and commonly employed additives such as copper co-catalysts or phase transfer catalysts. Furthermore, the material was also used in the oxidative Sonogashira coupling reaction of phenylboronic acid and phenylacetylene. The catalyst can be easily separated using an external magnet and can be reused several times. The feasibility of producing diphenylacetylene on a gram scale via the Sonogashira cross-coupling reaction was also investigated. Full article

Oligo(arylene ethynylene)s (OAEs) containing 4,5-(diethynylaryl)-1,2,3-triazoles with 3(OMe) and NR₂ substituents at the 5-position and bis-1,4-dialkoxybenzene moieties as spacers at the 4-position were obtained using the retro-Favorskii reaction as a key step. The most intense fluorescence was observed for OAEs with a trimethoxyphenyl substituent in THF solutions, with a quantum yield of up to 88%. Increasing the solvent polarity had minimal effect on the emission of trimethoxyphenyl substituted derivatives. A notable red shift in emission spectra was observed with increasing solvent polarity for OAEs 10a,g containing para-dimethylaminophenyl group. Their emission spectra in aqueous organic solutions revealed that an increase in water fraction in THF/water mixtures led to a bathochromic shift in emission spectra maxima accompanied by a hypochromic effect. An increase in intensity was observed in aqueous acetonitrile and DMSO. The maximum intensity was observed in DMSO solutions containing 30% water, which is attributed to aggregate-induced emission enhancement. Dynamic light scattering data also confirmed the formation of nanoscale aggregates in aqueous organic mixtures. Full article

Mycotoxins commonly contaminate grains and traditional Chinese medicinal materials, posing serious health risks to humans and animals. To address this issue, a magnetic microporous organic network (MMON) was synthesized via an in situ growth method and Sonogashira–Hagihara coupling for the simultaneous adsorption of seven mycotoxins, followed by UPLC-MS/MS detection. The optimized MMON featured a high surface area, uniform micropores, and rapid magnetic separation within 5 s. Structural and compositional analyses confirmed its tailored architecture, while DFT calculations revealed a pore confinement effect, π–π stacking, and hydrophobic interactions as the primary adsorption mechanisms. A magnetic solid-phase extraction (MSPE) method using 8 mg of MMON achieved adsorption equilibrium within 10 s in 5 mL of a 4 mg/L mycotoxin standard solution. The material maintained over 95% efficiency across ten reuse cycles at a low cost. Under optimal conditions, an MSPE-UPLC-MS/MS method with a low detection limit (0.002–0.15 μg/L), wide linear range (0.01–100.0 μg/L), large enrichment factor (20.1–21.9), low adsorbent dosage, and short extraction time was developed. The determination of mycotoxins in complex grain-based foods and herbal products was also realized with recoveries of 81.32% to 116.10%. This work offers a rapid, cost-effective, and high-throughput approach for mycotoxin detection, supporting quality control in food and herbal product safety. Full article

A carbon-supported palladium-containing polysiloxane macrocatalyst (Pd-PDMS) was developed for pharmaceutical-grade cross-coupling reactions. The catalyst demonstrates exceptional year-long stability at room temperature while maintaining full catalytic activity. Pd-PDMS efficiently promotes three pharmaceutically relevant reactions: Suzuki coupling (80% yield), copper-free Sonogashira coupling (90% yield at 55 °C), and Heck coupling (80% yield at 90 °C). The copper-free Sonogashira protocol eliminates toxic copper cocatalysts, phosphine ligands, and organic bases while operating under mild conditions. Most significantly, palladium contamination in products reaches ultra-low levels of 22 ppb (Sonogashira, Suzuki) and 167 ppb (Heck), representing a 60–450-fold improvement over European Medicines Agency requirements (10 ppm). The catalyst exhibits excellent recyclability without activity loss over multiple cycles, with simple washing protocols between uses. Scanning electron microscopy and X-ray photoelectron spectroscopy confirmed uniform Pd-PDMS coating on carbon fibers, while density functional theory calculations revealed specific coordination interactions between the palladium complex and carbon support at 3.26 Å distance. This convergence of pharmaceutical-grade metal contamination control, exceptional stability, and multi-reaction versatility establishes a significant advancement for sustainable cross-coupling catalysis in pharmaceutical applications. Full article

Background: Multitarget-directed ligands (MTDLs), particularly those combining cholinesterase inhibition with additional mechanisms, are promising candidates for Alzheimer’s disease (AD) therapy. Based on our previous identification of a dual-active coumarin derivative, we designed a new series of 7-alkoxyamino-3-(1,2,3-triazole)-coumarins. Methods: These compounds were synthesized by a new Sonogashira protocol and evaluated for AChE and BChE inhibition, enzymatic kinetics, molecular docking, neurotoxicity in SH-SY5Y cells, neuroprotection against H₂O₂-induced oxidative stress, and additional interactions with H₃R and MAOs. Results: All derivatives inhibited AChE with IC₅₀ values of 4–104 nM, displaying high selectivity over BChE (up to 686-fold). Kinetic and docking studies indicated mixed-type inhibition involving both CAS and PAS. The most potent compounds (1h, 1j, 1k, 1q) were non-neurotoxic up to 50 µM, while 1h and 1k also showed neuroprotective effects at 12.5 µM. Selected derivatives (1b, 1h, 1q) demonstrated multitarget potential, including H₃R affinity (K_i as low as 32 nM for 1b) and MAO inhibition (IC₅₀ of 1688 nM for 1q). Conclusions: This series of coumarin–triazole derivatives combines potent and selective AChE inhibition with neuroprotective and multitarget activities, highlighting their promise as candidates for AD therapy. Full article

Herein, we report a one-pot palladium- and ligand-free tandem Sonogashira coupling/regioselective 6-endo-dig oxacyclization reaction of 2,4-diiodo-1-methyl-imidazole-5-carboxylic acid with terminal alkynes mediated by Copper(I). This impressive approach offers a straightforward, practical, and efficient tandem procedure for accessing 2-alkynylated pyrano[4,3-d]imidazol-4-one in moderate to good yields with an exclusive 6-endo-dig oxacyclization. Notably, this cost-effective methodology demonstrates broad substrate compatibility with various commercially available aliphatic and (hetero)aromatic terminal alkynes. Furthermore, DFT studies were performed to elucidate the origin of this regioselective 6-endo-dig oxacyclization reaction. Full article

Mechanochemical and transition-metal-catalyzed reactions of alkynes, exhibiting significant advantages like short reaction time, solvent-free, high yield and good selectivity, were considered to be green and sustainable pathways to access functionalized molecules and obtained increasing attention due to the superiorities of mechanochemical processes and the reactivities of alkynes. The ball milling and CuI-catalyzed Sonogashira coupling of alkyne and aryl iodide avoided the use of common palladium catalysts. The mechanochemical Rh(III)- and Au(I)-catalyzed C–H alkynylations of indoles formed the 2-alkynylated and 3-alkynylated indoles selectively. The mechanochemical and copper-catalyzed azide-alkyne cycloaddition (CuAAC) between alkynes and azides were developed to synthesize 1,2,3-triazoles. Isoxazole could be formed through ball-milling-enabled and Ru-promoted cycloaddition of alkyne and hydroxyimidel chloride. In this review, the generation of mechanochemical and transition-metal-catalyzed reactions of alkynes was highlighted. Firstly, the superiority and application of transition-metal-catalyzed reactions of alkynes were briefly introduced. After presenting the usefulness of green chemistry and mechanochemical reactions, mechanochemical and transition-metal-catalyzed reactions of alkynes were classified and demonstrated in detail. Based on different kinds of reactions of alkynes, mechanochemical and transition-metal-catalyzed coupling, cycloaddition and alkenylation reactions were summarized and the proposed reaction mechanisms were disclosed if available. Full article

Tricyclic and tetracyclic lactone derivatives of thieno[2,3-b]pyrazine or thieno[2,3-b]quinoline, and 2H-pyrones were prepared using different methodologies. Pd/Cu-catalyzed Sonogashira coupling using Et₃N as a base, of methyl 7-bromothieno[2,3-b]pyrazine-6-carboxylate and (het)arylalkynes to yield the Sonogashira ester products, gave also the corresponding tricyclic lactones as minor products. However, the major products did not cyclize with TFA. Tricyclic lactones were then obtained by a tandem one-pot Sonogashira coupling and 6-endo-dig lactonization of 7-bromothieno[2,3-b]pyrazine-6-carboxylic acid with (het)arylalkynes, in good yields. Halogenated tricyclic lactones were synthesized by halocyclization using CuX and NXS. Tetracyclic lactones were synthesized through a Rh(III)-catalyzed formal [4+2] cycloaddition, between thieno[2,3-b]quinoline-2-carboxylic acid and internal alkynes, triggered by C-H activation, with the carboxylic group acting as a directing group. Using the SRB assay, the antitumor activity of both Sonogashira products and lactones was evaluated across five human cancer cell lines (CaCo-2, MCF-7, AGS, HeLa, NCI-H460). The best-performing compound was a Sonogashira product showing a GI₅₀ < 10 µM in all tumor cell lines and low toxicity in PLP2 cells. Additionally, antiparasitic testing against Trypanosoma brucei and Leishmania infantum revealed some compounds with IC₅₀ < 11 µM, though some level of cytotoxicity was observed in THP-1—derived macrophages. Full article

Viologens, i.e., quaternary 4,4′-bipyridinum salts, are a well-known class of functional organic compounds that have attracted in the past few decades a great deal of attention for their peculiar chemical and electrochemical properties and have therefore found numerous applications ranging from herbicides to electrochromic devices. In this paper, the synthesis and characterization of a novel viologen derivative are described. In the reported compound, the pyridinium nitrogen atoms have been quaternarized with the benzyl group and an additional unsaturated moiety, namely a 9,10-diethynylanthracene core, has been inserted between the charged pyridinium rings to extend the conjugation. Characterization by means of absorbance and diffuse reflectance UV–visible spectroscopy suggested intriguing optical and electronic properties, making this extended viologen a potential candidate for different optoelectronic applications. Full article

Coordination-driven Cu(I) complexes constitute an interesting class of materials with rich opto-electronic properties and diverse applications. Various homo- and heteroleptic Cu(I) complexes have been reported in the literature. In continuation with our quest for new materials, we report herein two novel coordination-driven self-assembled Cu(I) complexes: the homoleptic (1) and the heteroleptic (2) complexes based on the 6,6′-bis(phenylethynyl)-2,2′-bipyridine (L1) and 2,9-dimethyl-1,10-phenanthroline (dmph) ligands. L1 was prepared by a Pd(II)-catalyzed Sonogashira cross-coupling reaction between phenylactylene and 6,6′-dibromo-2,2′-bipyridine. Homo- and heteroleptic Cu(I) complexes were obtained by the self-assembly of L1 and dmph ligands. Complexes (1) and (2) were obtained in high yields, and are soluble in common organic solvents and stable at room temperature over a long period of time. The optical (absorption and emission) properties of both complexes were evaluated. The optical properties in solution are a function of the ligands and varied for the complexes. Complex (2) was also characterized by single-crystal X-ray diffraction and the intermolecular interaction was studied using Hirschfeld surface analysis. In the solid state, complex (2) exhibited four-coordinate distorted tetrahedral geometry around Cu(I). Density functional theory (B3LYP/6-311++G(d,p) was utilised to determine various molecular descriptors. Full article

The emergence of RNA viruses driven by global population growth and international trade highlights the urgent need for effective antiviral agents that can inhibit viral replication. Nucleoside analogs, which mimic natural nucleotides, have shown promise in targeting RNA-dependent RNA polymerases (RdRps). Starting from protected 5-iodouridine, we report the synthesis of hitherto unknown C5-substituted-(1,3-diyne)-uridines nucleosides and their phosphoramidate prodrugs. The modifications at C5 include 4-(trifluoromethyl)benzene (a), 4-pentyl-benzene (b), 3,5-dimethoxy-benzene (c), 4-(trifluoromethoxy)benzene (d), 3-aniline (e), 4-pyridine (f), 3-thiophene (g), C₆H₁₃ (h), 2-pyrimidine (i), cyclopropyl (j), and phenyl (k) groups. These compounds were synthesized using Sonogashira palladium-catalyzed reactions and nickel–copper-catalyzed C-H activation between various alkynes, yielding between 25% and 67%. The antiviral activities of obtained compounds were measured through HTS against RNA viruses including influenza H1N1 and H3N2, human respiratory syncytial virus (RSV), SARS-CoV-2, Zika, hepatitis C virus (HCV), Hepatitis E virus (HEV), as well as against coronavirus (HCoV-229E). Unfortunately, none of them showed promising antiviral activity, with less than 85% inhibition observed in the cell viability screening of infected cells. Full article

Bimetallic PdCu nanoparticles with different Pd:Cu ratios and morphologies can be synthesized and immobilized on a variety of support materials. Accordingly, PdCu nanoparticles can be efficiently applied as heterogeneous catalysts in a large number of organic transformations including C-C coupling and cross-coupling reactions. As related to their favorable electronic and structural interactions, the catalytic performances of PdCu bimetallic nanoparticles may be superior to monometallic species. The heterogeneous catalysts can be recovered and reused, and the presence of copper tends to reduce the cost of the expensive Pd catalyst, which is beneficial for industrial applications. Full article