Search Results (419)

In the last decades, numerous approaches have been explored for the cross-coupling of biaryl building blocks depending on the presence of boron sources. In fact, these changes have been catalyzed by transition metal complexes. This review focuses on the progress of the last decade in transition metal-catalyzed C–X borylation and direct C–H borylation, with emphasis on nickel-catalyzed C–H borylation, as effective and affordable protocols for the borylation of aryl substrates. In addition, Suzuki-type cross-coupling by activation of C–H, C–C, or C–N bonds is also reported. This study then offers an overview of recent advances for the synthesis of bi- and multi-aryls found in synthetic molecular complexes and natural products using the transition metal-catalyzed one-pot Miyaura-type C–X and C–H borylation–Suzuki coupling sequence. Full article

In this work, we described the synthesis of 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate by reacting 5-bromofuroic acid with methylparaben in the incorporation of DCC/DMAP (Steglich esterification) as coupling agents. Later on, we subsequently synthesized a series of 4-(methoxycarbonyl)phenyl 5-aryl furan-2-carboxylates (5a–5e) through Suzuki coupling catalyzed by palladium (0) between 4-(methoxycarbonyl)phenyl 5-bromofuran-2-carboxylate (3) with several substituted arylated and heteroaryl boronic acids (4). DFT calculations were computed to elucidate electronic structural features of synthesized molecules (5a–5e) and to validate these findings by correlating with theoretical and experimental spectroscopic analysis. Furthermore, geometrical optimization, thermodynamic features, as FMO orbitals, MESP maps, NLO behavior and reactivity descriptors, were also determined from the PBE0 D3BJ/def2-TZVP/SMD_1,4-dioxane theory level to confirm the structural features of synthesized molecules. Full article

1,3,4-Oxadiazoles containing boronic acid moieties are promising as a highly versatile class of compounds with significant utility across various scientific domains. The diverse synthetic methodologies for their preparation make these compounds valuable precursors for developing novel entities with tailored properties in medicinal chemistry, agrochemistry, and materials science. This review systematically compiles and discusses synthetic methods for the direct and indirect incorporation of boronic acid derivatives into 1,3,4-oxadiazole scaffolds. Understanding these strategies is particularly important because of their key role in modern synthetic transformations, especially Suzuki–Miyaura cross-coupling reactions, which enable easy access to a new generation of structurally diverse 1,3,4-oxadiazole-based compounds. The synthetic procedures and reactions discussed are based on the currently available literature, offering a comprehensive overview of this rapidly evolving field. Full article

A new π-conjugated acceptor–donor–acceptor small molecule, designed for applications in organic solar cells, containing a terthiophene core and indandione- and benzonitrile-based electron-withdrawing units, was synthesized via a multi-step process involving Suzuki–Miyaura cross-coupling and Knoevenagel condensation reactions. The structure was confirmed by NMR spectroscopy, HRMS, and its optoelectronic properties were evaluated by UV–vis spectroscopy and cyclic voltammetry. Full article

The efficient synthetic routes and evaluates cytotoxic profiles of denitroaristolochic acids II–V (DAA-II–V) were demonstrated in this study. Based on retrosynthetic analysis, a modular synthetic strategy was developed through Suzuki–Miyaura coupling, Wittig reaction, and bismuth triflate-catalyzed intramolecular Friedel–Crafts cyclization to efficiently construct the phenanthrene core. Process optimization significantly improved yields: aryl bromide intermediate A reached 50.8% yield via bromination refinement, while arylboronic ester intermediate B overcame selectivity limitations. Combining Darzens condensation with Wittig reaction enhanced throughput, achieving 88.4% yield in the key cyclization. Structures were confirmed by NMR and mass spectra. CCK-8 cytotoxicity assays in human renal proximal tubular epithelial cells revealed distinct toxicological profiles: DAA-III and DAA-IV exhibited IC₅₀ values of 371 μM and 515 μM, respectively, significantly higher than the nitro-containing prototype AA-I (270 μM), indicating that the absence of nitro group attenuates but does not eliminate toxicity, potentially via altered metabolic activation. DAA-II and DAA-V showed no detectable cytotoxicity within assay limits, suggesting reduced toxicological impact. Structure–activity analysis exhibited that the nitro group is not essential for cytotoxicity, with methoxy substituents exerting limited influence on potency. This challenges the conventional DNA adduct-dependent toxicity paradigm, implying alternative mechanisms like oxidative stress or mitochondrial dysfunction may mediate damage in denitro derivatives. These systematic findings provide new perspectives for AA analog research and a foundation for the rational use and safety assessment of Aristolochiaceae plants. Full article

An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer’s disease. The conditions for the Suzuki–Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman’s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one derivative exhibited the highest inhibitory potency, with an IC₅₀ value of 6.084 ± 0.26 μM. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer’s disease. Full article

In this study, novel fluorescent 5-aryl-2-styryl-3H-indole derivatives were efficiently synthesized from 4-bromophenylhydrazine hydrochloride using the microwave-accelerated one-pot technique, which includes Fischer synthesis, Suzuki cross-coupling, and Knoevenagel condensation. The structural assignments of the synthesized compounds were based on ¹H, ¹³C, ¹⁵N, and ¹⁹F NMR; IR spectroscopy; and HRMS spectral data. The optical properties of the newly obtained styryl-indole dyes were studied using UV-vis and fluorescence spectroscopy, which clearly demonstrated that the derivatives substituted with electron-donating or -withdrawing groups exhibited varying emission shifts and quantum yields ranging from negligible to high. Full article

Background/Objectives: Colony stimulating factor 1 receptor kinase (CSF1R) is a well-validated molecular target in drug discovery for various reasons. Based on the structure of an early lead molecule identified in our lab and the marketed drug Pexidartinib (PLX3397), we merged fragments of Pexidartinib with our pyrrolo[2,3-d]pyrimidine nucleus, and the idea was supported by initial molecular docking studies. Thus, several new compounds were synthesized with Pexidartinib fragments on C4, C5, and C6 on the pyrrolopyrimidine scaffold using molecular hybridization. Methods: Nine final products were synthesized using a combination of Buchwald-Hartwig and Suzuki-Miyaura cross-coupling reactions in three to four steps and in good yields. The analogues were subsequently profiled as CSF1R inhibitors in enzymatic and cellular assays, and ADME properties were evaluated for some derivatives. Results: N-Methyl-N-(3-methylbenzyl)-6-(6-((pyridin-3-ylmethyl)amino)pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (12b) emerged as the most potent CSF1R inhibitor, showing low-nanomolar enzymatic activity, cellular efficacy, and favorable ADME properties, highlighting its promise as a lead compound for further development. Conclusions: These findings suggest that combining structural elements from previously reported CSF1R inhibitors such as Pexidartinib could guide the development of improved drug candidates targeting this kinase. Full article

Unlike the wide number of natural biflavonoids, natural bichalcones are a rare and even less studied class. Nevertheless, some of them have proved their interest in the fight against cancer through their cytotoxic activity against human tumor cell lines. The aim of this study was to synthesize a novel bichalcone: 3′,3‴,4,4′,4″,4‴,5′,5‴-octamethoxy-2,3″-bichalcone 1. The most efficient synthetic pathway was the Suzuki–Miyaura reaction between a boronated chalcone and a brominated one. Full article

This study presents a sustainable, environmentally friendly synthetic route for the production of key intermediates in losartan using palladium nanoparticles (PdNPs) derived from a brown seaweed, Sargassum incisifolium, as a recyclable nanocatalyst. A key intermediate, biaryl, was synthesized with an excellent yield (98%) via Suzuki–Miyaura coupling between 2-bromobenzonitrile and 4-methylphenylboronic acid, catalyzed using bio-derived PdNPs under mild conditions. Subsequent bromination using N-bromosuccinimide (NBS) under LED light, followed by imidazole coupling and tetrazole ring formation, allowed for the production of losartan with an overall yield of 27%. The PdNP catalyst exhibited high stability and recyclability, as well as strong catalytic activity, even at lower loadings, and nitrosamine formation was not detected. While the overall yield was lower than that of traditional industrial methods, this was due to the deliberate avoidance of the use of toxic reagents, hazardous solvents, and protection/deprotection steps commonly used in conventional routes. This trade-off marks a shift in pharmaceutical process development, where environmental and safety considerations are increasingly prioritized in line with green chemistry and regulatory frameworks. This study provides a foundation for green scaling up strategies, incorporating sustainability principles into drug synthesis. Full article

This study reports the synthesis, characterization, and property analysis of four novel multilayer 3D polymers (1A to 1D) with 1,3-phenyl bridge architectures spanning 248 to 320 layers. High-molecular-weight polymers were successfully synthesized via catalytic Suzuki–Miyaura cross-coupling over a four-day reaction period. Structures, thermal, and optical properties were examined using multiple analytical techniques. Fourier transform-infrared (FT-IR) spectroscopy was used to study the hydrogen bonding within the polymer system, suggesting the formation of the polymer through the Suzuki–Miyaura coupling reaction. Ultraviolet–visible (UV-vis) spectroscopy indicated strong electronic delocalization, with maximum absorbance peaks between 257 and 280 nm. Thermal characterization, using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), was used to investigate the thermal stability. TGA results showed that all four polymers retained more than 20% of their initial mass at 1000 °C, indicating good thermal stability across the series. DSC analysis revealed that polymer 1A exhibited a glass transition temperature (Tg) of 167 °C, indicating the presence of a network formed by aromatic conjugation and hydrogen bonding. Furthermore, the subtle Tg step observed for 1A suggests a degree of crystallinity within the polymer matrix, which was further supported by X-ray diffraction (XRD) analysis. Aggregation-induced emission (AIE) experiments provided further insights into intermolecular packing, and scanning electron microscopy (SEM) contributed to a better understanding of the morphology of the obtained polymers. These results highlight the potential of these polymers as thermally stable and conductive materials for biomedical and industrial applications. Full article

Herein, we report the first mechanochemical strategy for the Ru-catalyzed deoxygenative borylation of free phenols via C–O bond cleavage. This Ru-catalyzed phenolic borylation approach has been successfully extended to the Suzuki–Miyaura-type cross-coupling of phenols with aryl bromides. The protocol accepts a wide scope of phenolic substrates, allowing the synthesis of aryl pinacolboranes and biphenyl structures in excellent yields and serving as a better alternative to classical cross-coupling reactions in the context of pot, atom, and step economy synthesis. Full article

Mg-Al hydrotalcite (HT), comprising Mg²⁺ and Al³⁺ as layered hydroxide cations, was synthesized via a hydrothermal process at 200 °C. The HT was evaluated as a carrier, and subsequently, palladium was immobilized on the surface of the hydrotalcite (HT/NC), resulting in the development of an innovative biomass-based palladium catalyst. The catalyst underwent analysis by X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). It exhibited remarkable catalytic efficiency and superior activity as a catalyst in the Suzuki–Miyaura coupling reaction in water. The catalyst was recyclable without a decline in activity and could be utilized more than 10 times, with exceptional yield. Furthermore, the commercially accessible anticancer drug Elacestrant can be readily produced using this protocol. Full article

Background/Objectives: The isatin nucleus is a privileged scaffold in drug discovery, particularly due to its proven relevance in anticancer research. Developing reusable heterogeneous 3D catalysts for drug synthesis represents a critical challenge in both industrial and academic contexts. This multi and interdisciplinary work aimed to design and synthesize a novel 3D-printed silica-based porous catalyst functionalized with palladium, evaluate its catalytic performance in isatin drug synthesis, and assess the antiproliferative activity of the resulting compounds against tumor cell lines such as HeLa, MCF-7, and MDA-MB231. Methods: The novel multifaceted approach to synthesizing this heterogeneous catalyst involved the surface growth of a metal–organic framework (ZIF-8) on 3D-printed silica support, followed by potassium silicate coating and pyrolysis. Results: After detailed physicochemical characterization, the catalyst was tested in challenging “double” palladium-catalyzed cross-coupling reactions (Suzuki, Stille, and Heck), demonstrating robustness, reusability, and high efficiency in producing bis-1,5-aryl, alkynyl, and alkenyl-isatin derivatives. Importantly, no leaching of palladium species was detected during the catalytic cycles, further underscoring the stability of the system. These isatin-based compounds exhibited remarkable cytotoxicity, with selective molecules achieving nanomolar potency against MCF-7 cells, surpassing reference drugs such as doxorubicin and sunitinib. Conclusions: This study not only introduces a novel strategy for fabricating porous heterogeneous catalysts from sintered surfaces but also highlights new biomolecules with promising applications in cancer research. Full article

Canthin-6-one alkaloids have consistently attracted the interest of medicinal chemists due to their wide range of promising bioactivities, including antitumor, antifungal, antibacterial, and antiviral properties. However, their low natural abundance in plants has constrained the further exploration of their potential bioactivities. This study reports a comprehensive synthesis of canthin-6-one alkaloids, utilizing key Suzuki coupling and Cu-catalyzed amidation reactions to construct their core scaffold. Derivatives were synthesized with Koenig–Knorr glycosylation for the further modification of synthetic canthin-6-ones. The antimicrobial activities of the synthesized compounds were evaluated against C. albicans, C. neoformans, S. aureus and E. coli using the micro-dilution method. In total, 17 compounds were synthesized, including nine canthin-6-ones. Notably, alkaloids 4, 5, 7 and 12-13 were prepared for the first time, along with 8 new derivatives. Their structures were confirmed by NMR and MS analyses. At 50 µg/mL, the alkaloids 1-4 and 9 exhibited antimicrobial properties against C. albicans, C. neoformans and S. aureus. The antimicrobial activity of alkaloids 2, 4-5 and 12-13 against these four microbial human pathogens is reported here for the first time. Overall, this research not only advances our understanding of canthin-6-one alkaloid synthesis, but also provides a foundation for developing novel compounds with pharmaceutical properties. Full article