Search Results (128)

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

The semi-synthesis of the (5R,7R,11bR)-9-(di(1H-indol-3-yl)methyl)-4,4,7,11b-tetramethyl-1,2,3,4,4a,5,6,6a,7,11,11a,11b-dodecahydrophenanthro[3,2-b]furan-5-yl acetate was performed via a pseudo-multicomponent reaction involving a double Friedel–Crafts alkylation between the natural product-derived aldehyde 6β-acetoxyvouacapane and the corresponding indole. The transformation was carried out under solvent-free mechanochemical conditions using mortar and pestle grinding, with ZnCl₂ as the catalyst. Structural elucidation of the target compound was accomplished using 1D and 2D NMR spectroscopy (¹H, ¹³C, COSY, HSQC, and HMBC), FT-IR, and high-resolution mass spectrometry (HRMS). Full article

Multicomponent reactions (MCRs) enable the efficient assembly of complex small molecules via multiple bond-forming events in a single step. However, individual MCRs typically yield products with similar core structures, limiting access to larger, more intricate scaffolds. Strategic selection of reactants allows the combination of distinct MCRs, thus facilitating the synthesis of advanced molecular architectures with potential biological significance. Using our previously reported method for performing the aza-Friedel Crafts multicomponent reaction under green heterogeneous conditions, we have incorporated some of the obtained products into diverse multicomponent reactions to generate, in an unprecedent approach, eight novel products, some of which were also characterized by two-dimensional NMR techniques. The biological properties of such products are under investigation. Full article

Hydroformylation is one of the most widely applied homogeneous catalytic processes in the chemical industry, constituting the predominant manufacturing platform for aldehyde synthesis at commercial scales. Nevertheless, hydroformylation shares with traditional homogeneous catalysis the inherent limitation of difficult catalyst recovery and recycling. Developing heterogeneous catalysts for such reactions is thus critically needed. Herein, a stable nitrogen-rich covalent triazine framework (CTF) was synthesized via a mild Friedel–Crafts alkylation method and employed as a support for Rh single-atom catalysts (Rh/CTF-TPA). In the hydroformylation of 1-decene, the Rh/CTF-TPA catalyst exhibits an exceptional reaction efficiency (TOF > 1900 h⁻¹), outperforming the homogeneous Rh(CO)₂(acac). Experimental and characterization results revealed that the CTF support enhances catalytic performance through two key mechanisms: (1) strong enrichment of reactants within its special structure, and (2) efficient dispersion of Rh single-atom sites stabilized by abundant nitrogen coordination. This work demonstrates a rational design strategy for heterogeneous hydroformylation catalysts by leveraging nitrogen-rich porous frameworks to synergistically optimize metal anchoring and reactant enrichment, offering a promising alternative to conventional homogeneous systems. Full article

Natural gas purification and the mitigation of carbon dioxide (CO₂) emissions from flue gases are critical steps in alleviating the greenhouse effect and significantly mitigate multiple environmental challenges associated with global warming. Hypercrosslinked polymers (HCPs) have become a hot topic as prospective adsorbents for gas purification and separation, owing to their low cost and scalability. Hence, TPB-Ben, TPB-Nap, and TPB-Ant were synthesized through a solvent knitting strategy, with the modification in the size of the monomers serving as a distinctive feature. This alteration aimed to explore the impact of phenyl ring quantity on the polymers’ gas adsorption and separation efficiency. All HCPs showed outstanding selective separation capability of CO₂ from CO₂/CH₄ and CO₂/N₂ mixtures, such as TPB-Ben-3-2 (CO₂/CH₄: 10.77; CO₂/N₂: 59.72), TPB-Nap-3-2 (CO₂/CH₄: 9.12; CO₂/N₂: 61.31), and TPB-Ant-3-2 (CO₂/CH₄: 10.00; CO₂/N₂: 62.89), which could be potential candidate adsorbents for natural gas purification and CO₂ capture. Considering the mild reaction conditions, low cost, efficient gas adsorption, and the potential for scalable production, these polymers are considered ideal selective solid adsorbents for capturing CO₂. This further highlights the significance of the solvent knitting strategy. Full article

Because of the continuous interest in ferrocene chemistry, there is a sustained demand for various ferrocenic building blocks, especially small molecules with useful chemical functional groups, sometimes containing multiple groups. Our interest in ferrocene ketoesters (ω-ferrocenyl-ω-ketoesters) was motivated by the synthesis of esters and subsequently alcohols of ferrociphenols. However, from a bibliographic survey, only one publication dated from 1964 reports the two-step synthesis (six-step synthesis from ferrocene) of methyl 2-ferrocenyl-2-oxoacetate, the simplest member of this family of compounds, with no further developments since. We hypothesized that a simpler method might exist, such as the Friedel–Crafts method. By focusing on our experiments to use aluminum trichloride as the catalyst, we managed to achieve the synthesis of FcCOCOOMe in a single step, albeit with a very low yield, regardless of reaction time, temperature, amount of aluminum chloride and reagents concentration. Nevertheless, considering the time saved, simplicity, and the use of less hazardous and less expensive reagents, this method offers certain advantages for synthesizing this building block. Full article

Over the past three decades, β-lactones have emerged as valuable intermediates for producing diverse industrial chemicals and biodegradable polymers. The ring-expansion carbonylation (REC) of epoxides has become an atom-economical and direct approach to β-lactone production, leveraging readily available carbon monoxide and epoxides. While homogeneous catalysts, particularly bimetallic [Lewis acid]⁺[Lewis base]⁻-type systems, have demonstrated exceptional activity and selectivity, issues like recycling and separation limit the industrial scalability. Heterogenized catalysts offer advantages such as ease of separation and reusability but suffer from reduced efficiency. Recent advancements in porous polymer-based heterogeneous systems, including immobilized cobaltate anions, address these challenges by combining high surface areas with enhanced catalytic performance. Herein, we explore the evolution of homogeneous to heterogeneous REC catalysts, highlighting emerging porous materials and their potential for scalable β-lactone synthesis. Future directions emphasize overcoming the remaining barriers to establish robust, efficient, and sustainable catalytic processes. Full article

An efficient stereoselective synthesis of 10-hydroxy-10-(1H-indol-3-yl)-9-(10H)-phenanthrene derivatives was realized through an organocatalyzed Friedel–Crafts reaction of phenanthrenequinones and indoles using a (S,S)-dimethylaminocyclohexyl-squaramide as the catalyst. Under the optimized conditions, the desired chiral products were obtained in good yields (73–90%) with moderate to high ee values (up to 97% ee). Two pairs of synthesized enantiomers were subjected to evaluation of their antiproliferative activities on four types of human cancer cell lines and one human umbilical vein endothelial cell line using the CCK-8 assay. The results indicated that stereoselectivity had obvious impacts on biological activity. (S)-4g was found to have optimal cytotoxicity against the A549 cell line and a good safety profile for human normal cells, which was better than the inhibitory activity of the positive control drug (doxorubicin). Full article

This study aimed to investigate the properties of tin(II) oxide (SnO) as an unconventional cross-linking agent for chloroprene (CR) and styrene–butadiene (SBR) rubbers compositions. The use of tin(II) oxide results from the need to reduce the use of zinc oxide as a cross-linking agent due to environmental regulations and its toxic impact on aquatic environments. The studied elastomeric blends can be cross-linked with tin(II) oxide, and the results demonstrate the significant potential of this oxide in such applications. The CR/SBR vulcanizates cross-linked with SnO exhibit good mechanical properties and a high degree of cross-linking. The studies clearly show that the proportions of both rubbers as well as the amount of tin(II) oxide used influence the cross-linking of the CR/SBR blends and the properties of vulcanizates. FTIR spectrum analysis allowed the identification of the cross-linking mechanism, which followed the Friedel–Crafts alkylation reaction mechanism. The AFM analysis determined the miscibility of the rubbers and interelastomeric reactions, proving that the rubbers studied are partially miscible. The results of the oxygen index measurements indicated that the obtained vulcanizates showed flame resistance and self-extinguishing properties. Multivariate regression was performed to fit the models to the experimental value and to determine the influence of the content of the cross-linking agent and the CR and SBR proportions on the properties of the blends. Full article

Hypercrosslinked polymers (HCPs) constructed by the Friedel–Crafts alkylation reaction of aromatic compounds have emerged as a new class of porous materials with unique merit. Herein, a HCP named HCP-TPB was coated onto a capillary column through in situ synthesis. The prepared column exhibited a nonpolar nature, and the column efficiency for n-dodecane was 3003 plates m⁻¹. Moreover, the relative standard deviations of retention time and peak area for six replicate injections of the C3–C6 were lower than 0.1% and 1.5%, respectively. The results of this study showed that it is very promising to utilize HCPs as stationary phases for the separation of C3–C6. Full article

Carbon–carbon bond formation represents a key reaction in organic synthesis, resulting in paramount importance for constructing the carbon backbone of organic molecules. However, traditional metal-based catalysis, despite its advantages, often struggles with issues related to efficiency, selectivity, and sustainability. On the other hand, while biocatalysis offers superior selectivity due to an extraordinary recognition process of the substrate, the scope of its applicable reactions remains somewhat limited. In this context, Artificial Metalloenzymes (ArMs) and Metallo Peptides (MPs) offer a promising and not fully explored solution, merging the two fields of transition metal catalysis and biotransformations, by inserting a catalytically active metal cofactor into a customizable protein scaffold or coordinating the metal ion directly to a short and tunable amino acid (Aa) sequence, respectively. As a result, these hybrid catalysts have gained attention as valuable tools for challenging catalytic transformations, providing systems with new-to-nature properties in organic synthesis. This review offers an overview of recent advances in the development of ArMs and MPs, focusing on their application in the asymmetric carbon–carbon bond-forming reactions, such as carbene insertion, Michael additions, Friedel–Crafts and cross-coupling reactions, and cyclopropanation, underscoring the versatility of these systems in synthesizing biologically relevant compounds. Full article

Ambient condition-determined chemical CO₂ fixation affords great promise for remitting the pressure of CO₂ release. The construction of a microporous environment easily captures CO₂ molecules around the reactive sites of the catalyst to reinforce the reaction process. Herein, multi-hydroxyl-containing hyper-crosslinked organic polymers (HCPs-OH-n) are synthesized by the polymerization of 1,4-dichlorobenzyl (DCX) and m-trihydroxybenzene in the monosaccharide form in a Friedel–Crafts alkylation hypercrosslinking process (FCAHP). By tuning the DCX ratio in the FCAHP, the structural properties can be regulated to create a more microporous surface in the HCPs-OH-n; meanwhile, the formed multi-hydroxyl species in the microporous environment could induce the easy interaction between hydroxyls and epoxides by forming a hydrogen bond, which improves the activation of epoxides during the cycloaddition reaction to synthesize the cyclic carbonates at ambient conditions. The structural properties suggest that HCPs-OH-n possess a large surface area with appreciable microporous and mesoporous distribution. As expected, the HCPs-OH-3 bearing the most abundant mesoporosity affords the highest reactivity in the chemical CO₂ fixation to cyclic carbonates and is endowed with rational recoverability. Full article

Chiral pincer complexes, characterized by their rigid tridentate coordination framework, have emerged as powerful catalysts in asymmetric synthesis. This review provides a comprehensive overview of recent advancements in the development of chiral pincer-type ligands and their corresponding transition metal complexes. We highlight the latest progress in their application across a range of catalytic asymmetric reactions, including the (transfer) hydrogenation of polar and non-polar bonds, hydrophosphination, alkynylation, Friedel-Crafts reactions, enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones, enantioselective hydrosilylation, as well as Aza–Morita–Baylis–Hillman reactions. The structural rigidity and tunability of chiral pincer complexes enable precise control over stereoselectivity, resulting in high enantioselectivity and efficiency in complex molecular transformations. As the field advances, innovations in ligand design and the exploration of new metal centers are expected to expand the scope and utility of these catalysts, bearing significant implications for the synthesis of enantioenriched compounds in pharmaceuticals, materials science, and beyond. Full article

Meroterpenoid-type marine natural compounds have attracted an increasing amount of attention due to their peculiar chemical structures and their potential for the development of therapeutically important probes. Within this group of substances pelorol stands out; it is a natural compound isolated from marine organisms with a unique structure and an interesting biological profile. In this article, we summarize and highlight the most interesting aspects of the synthetic procedures towards this compound, which have two common key steps. The first is the coupling of a drimanyl derivative with a compound derived from an arene. The second is a Friedel–Crafts cyclization which forms the C ring of the natural product. Despite the synthetic advances achieved so far, we consider that a more efficient synthetic procedures could be carried out, since their synthetic routes are difficult to scale up due to numerous reaction steps and the limitations imposed by the use of some reagents. In this article, we present a new and versatile retrosynthetic analysis of (−)-pelorol and analogs, which is highly desirable for their easy preparation and subsequent broad study of their biological activities. This is a retrosynthetic route that could improve those reported in the literature in terms of cost-effectiveness. Full article

As an important class of nitrogen-containing fused heterocyclic compounds, imidazo[1,2-a]pyridines often exhibit significant biological activities, such as analgesic, anticancer, antiosteoporosis, anxiolytic, etc. Using Y(OTf)₃ as a Lewis acid catalyst, a simple and efficient method has been developed for the synthesis of C₃-alkylated imidazo[1,2-a]pyridines through the three-component aza-Friedel–Crafts reaction of imidazo[1,2-a]pyridines, aldehydes, and amines in the normal air atmosphere without the protection of inert gas and special requirements for anhydrous and anaerobic conditions. A series of imidazo[1,2-a]pyridine derivatives were obtained with moderate to good yields, and their structures were confirmed by ¹H NMR, ¹³C NMR, and HRMS. Furthermore, this conversion has the advantages of simple operation, excellent functional group tolerance, high atomic economy, broad substrate scope, and can achieve gram-level reactions. Notably, this methodology may be conveniently applied to the further design and rapid synthesis of potential biologically active imidazo[1,2-a]pyridines with multifunctional groups. Full article