Search Results (94)

Herein, we report an efficient one-pot synthesis of bridged aminodiperoxides via a three-component reaction of 1,5-diketones with geminal bishydroperoxides and ammonium acetate. The synthesized aminodiperoxides are stable despite containing an unprotected secondary NH-group adjacent to two peroxide functionalities. Under optimal conditions, the reaction affords aminodiperoxides in high yields (up to 88%) with outstanding selectivity and high atom economy, thereby eliminating the need for column chromatographic purification. The synthesized aminodiperoxides exhibit potent cytotoxicity and remarkable selectivity toward Jurkat, K562, and A549 cancer cell lines, and are significantly superior to the clinically used anticancer agent camptothecin. Among all tested compounds, 3ec is the most promising candidate, exhibiting high activity and selectivity toward all tested cell lines (Jurkat: CC₅₀ = 12.9 µM, SI = 67.09; K562: CC₅₀ = 19.6 µM, SI = 44.28; A549: CC₅₀ = 48.2 µM, SI = 17.98). Furthermore, a novel class of fungicidal compounds has been discovered. The aminodiperoxides exhibit fungicidal activity against phytopathogenic fungi, in some cases comparable to the commercial fungicide Triadimefon. Full article

A one-pot synthetic methodology that combines an Ugi-Zhu three-component reaction (UZ-3CR) with a cascade sequence (intermolecular aza Diels–Alder cycloaddition/intramolecular N-acylation/decarboxylation/dehydration) using microwave-heating conditions, ytterbium (III) triflate (Yb(OTf)₃) as the catalyst, and chlorobenzene (for the first time in a multi-component reaction (MCR)) as the solvent, was developed to synthesize twelve new fluorinated-pyrrolo[3,4-b]pyridin-5-ones containing a 4-amino-7-chloroquinoline moiety, yielding 50–77% in 95 min per product, with associated atom economies around 88%, also per product. Additionally, by in vitro tests, compounds 19d and 19i were found to effectively stop early SARS-CoV-2 replication, IC₅₀ = 6.74 µM and 5.29 µM, at 0 h and 1 h respectively, while cell viability remained above 90% relative to the control vehicle at 10 µM. Additional computer-based studies revealed that the most active compounds formed strong favorable interactions with important viral proteins (M_pro, NTDα and NTDo) of coronavirus, supporting a two-pronged approach that affects both how the virus infects the cells and how it replicates its genetic material. Finally, quantum chemistry analyses of non-covalent interactions were performed from Density-Functional Theory (DFT) to better understand how the active compounds hit the virus. Full article

The title compound, C₂₆H₂₁BrN₂O₅ (Compound 4), was obtained via our previously described procedure with modifications, i.e., via a facile one-pot three component reaction starting from commercially available materials. Compound 4 was crystallized from nitromethane. It crystalized in a triclinic crystal system, in the P-$\overline{1}$ space group. The crystal structure of 4 is described herein. Hirsfeld surface analysis, generated by the Crystal Explorer 21 software, was used to visualize the intermolecular close contacts in the title compound. The electrostatic, dispersion, and total energies in the crystal structure were calculated using the same program. Full article

Background: HIV-1 RT inhibitors were the first drugs approved to treat AIDS and remain key components of highly active antiretroviral therapy (HAART). While HAART effectively suppresses viral replication and slows disease progression, it has limitations, including long-term side effects and the emergence of drug-resistant strains, highlighting the need for new treatments. Objectives: Based on our previous experience, and insights from existing inhibitors of HIV-1 RT and RNase H, we aim to design and synthesize safer, multifunctional molecules. Methods: Using molecular docking studies, these compounds will incorporate pharmacophores targeting multiple stages of the HIV life cycle to enhance efficacy, reduce resistance, and improve pharmacokinetics. The compounds were synthesized via a one-pot three component reaction. The synthesized compounds were identified using spectroscopy and tested in vitro for activity against key HIV targets, including RNA-dependent DNA polymerase (RDDP) and RNAse H. Results: Among the synthesized compounds, several demonstrated strong inhibitory activity, with compound 11 showing IC₅₀ values comparable to the reference drug Nevirapine, and compound 4 exhibiting dual inhibition of both RT and RNase H activities. Conclusions: These findings emphasize the importance of a multidisciplinary approach, combining computational modeling with experimental validation, to identify promising leads for therapeutic development. Full article

Bacterial contamination is a major public health concern on a global scale. Treatment resistance in bacterial infections is becoming a significant problem that requires solutions. We were interested in obtaining new polymeric functionalized compounds with antibacterial properties. Three components (polymeric amine, aldehyde, and phosphite) were used in the paper in a modified “one-pot” Kabachnik–Fields reaction, in tetrahydrofuran at 60 °C, to create the N-C-P skeleton in aminophosphonate groups. Two copolymers were thus prepared starting from an acrylonitriledivinylbenzene (AN-15%DVB) copolymer containing pendant primary amine groups modified by grafting aminophosphonate groups, i.e., aminobenzylphosphonate (Bz-DVB-AN) and aminoethylphosphonate (Et-DVB-AN). The two copolymers were characterized by FT-IR spectroscopy, SEM-EDX, TGA, and antibacterial properties. It was shown that the novel products have antibacterial qualities against S. aureus and E. coli bacteria. The sample with the strongest antibacterial activity was Et-DVB-AN. We assessed how well the Weibull model and the first-order kinetic model represent the inactivation of microbial cells in our samples. The main advantage of the new antibacterial agents developed in this work is their easy recovery, which helps to avoid environmental contamination. Full article

This study explores a sustainable method for synthesizing quinazoline derivatives through visible light-driven photocatalysis using curcumin-sensitized titanium dioxide (TiO₂) nanoparticles. A one-pot, three-component reaction involving aldehydes, urea/thiourea, and dimedone was utilized to efficiently produce quinazoline compounds. The photocatalytic performance of curcumin-sensitized TiO₂ (Cur-TiO₂) was compared to pure TiO₂ (P-TiO₂), with Cur-TiO₂ showing significantly enhanced activity. Under optimized conditions—light intensity of 100 mW/cm², catalyst concentration of 1 mg/mL, and a reaction time of 40 min—a 97% product yield was achieved. The Cur-TiO₂ catalyst demonstrated excellent reusability, maintaining high efficiency over four consecutive cycles with minimal performance loss. This work underscores the potential of natural dye sensitization to extend light absorption of TiO₂ into the visible spectrum, providing an eco-friendly and cost-effective approach to sustainable organic synthesis. Full article

The one-pot multicomponent aza-Morita–Baylis–Hillman (MBH) reaction was performed under green conditions using 1,4-diazabicyclo[2.2.2]octane (DABCO) and Amberlyst^® 15 as a co-catalyst, at ambient temperature and under negligible amounts of non-hazardous solvent. A number of α-methylene-β-amino acid derivatives were produced in good to excellent yields from different arylaldehydes, p-toluenesulfonamide and α,β-unsaturated carbonyl compounds. The environmental benignity of the process is accounted by the low E-factor (0.7) and high atom economy (95%) values obtained. Full article

We investigated one-pot, three-component, and stepwise reactions of malononitrile and salicylic aldehydes (salicylic, 5-bromsalicylic) with N,N-nucleophiles, such as hydrazine hydrate, nitrobenzhydrazides, and o-phenylenediamine, under various conditions. This work reports on the synthesis of novel chromeno[4,3-c]pyrazoles and chromeno[4,3-e][1,4]diazepines. The influence of reaction parameters, such as solvent type and temperature, was studied. The structures of the synthesized compounds were established using spectroscopic data (IR, NMR). Full article

In this contribution, propylamine-functionalized cellulose (Cell-Pr-NH₂) was employed as the catalyst in the three-component reaction between hydroxylamine hydrochloride and various types of aryl/heteroaryl aldehydes, ethyl acetoacetate/ethyl 4-chloroacetoacetate, or ethyl 3-oxohexanoate. The result of these experiments was the formation of 3,4-disubstituted isoxazol-5(4H)-one heterocycles. The desired five-membered heterocyclic compounds were obtained in good to high yields at room temperature. The investigation of different solvents led us to the conclusion that water is the best solvent to perform the current one-pot, three-component reactions. Attempts to find the optimal catalyst loading clearly showed that 14 mg of cell-Pr-NH₂ seems to be sufficient to carry out the reactions. This method has highlighted some principles of green chemistry including less waste generation, atom economy, use of water as an environmentally friendly solvent, and energy saving. Purification without chromatographic methods, mild reaction conditions, simple work-up, low-cost reaction medium, saving time, and obtainable precursors are other notable features of this one-pot fashion. Full article

Anthranilic acids, salicylaldehydes and arylboronic acids reacted in EtOH/H₂O (1/3) at 150 °C under microwave irradiation for 1 h to give, in excellent yields and purity, twenty-three bridgehead bicyclo[4.4.0]boron heterocycles via one-pot, three-component green synthesis. The scope and the limitations of the reactions are discussed in terms of the substitution of ten different anthranilic acids, three salicylaldehydes and three arylboronic acids. The replacement of salicylaldehyde with o-hydroxyacetophenone demanded a lipophilic solvent for the reaction to occur. Eight novel derivatives were isolated following crystallization in a toluene-containing mixture that included molecular sieves. The above one-pot, three-component reactions were completed under microwave irradiation at 180 °C within 1.5 h, thus avoiding the conventional prolonged heating reaction times and the use of a Dean–Stark apparatus. All derivatives were studied for their affinity to calf thymus DNA using proper techniques like viscosity and UV–vis spectroscopy, where DNA-binding constants were found in the range 2.83 × 10⁴–8.41 × 10⁶ M⁻¹. Ethidium bromide replacement studies using fluorescence spectroscopy indicated Stern–Volmer constants between 1.49 × 10⁴ and 5.36 × 10⁴ M⁻¹, whereas the corresponding quenching constants were calculated to be between 6.46 × 10¹¹ and 2.33 × 10¹² M⁻¹ s⁻¹. All the above initial experiments show that these compounds may have possible medical applications for DNA-related diseases. Full article

Novel fluorescent pyrazole-containing boron (III) complexes were synthesized employing a one-pot three-component reaction of 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-aminobenzenecarboxylic acids, and boronic acids. The structures of the novel heterocyclic compounds were confirmed using ¹H-, ¹³C-, ¹⁵N-, ¹⁹F-, and ¹¹B-NMR, IR spectroscopy, HRMS, and single-crystal X-ray diffraction data. The photophysical properties of the obtained iminoboronates were investigated using spectroscopic techniques, such as UV–vis and fluorescence spectroscopies. Compounds display main UV–vis absorption maxima in the blue region, and fluorescence emission maxima are observed in the green region of the visible spectrum. It was revealed that compounds exhibit fluorescence quantum yield up to 4.3% in different solvents and demonstrate an aggregation-induced emission enhancement effect in mixed THF–water solutions. Full article

We disclose a direct approach to the diastereoselective synthesis of phosphorus substituted N-acylaziridines based on a one-pot ZnCl₂-catalyzed Joullié–Ugi three-component reaction of phosphorylated 2H-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array of N-acylaziridines in moderate-to-good yields and up to 98:2 dr for substrates over a wide scope. The relevance of this synthetic methodology was achieved via a gram-scale reaction and the further derivatization of the nitrogen-containing three-membered heterocycle. The diastereo- and regioselective ring expansion of the obtained N-acylaziridines to oxazole derivatives was accomplished in the presence of BF₃·OEt₂ as an efficient Lewid acid catalyst. Full article

This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds 4a–l, via a convenient one-pot three-component Hantzsch reaction. This approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, and interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as a promising compound, demonstrating robust antioxidant activity, the ability to activate Nrf2-ARE pathways, as well as calcium channel blockade and cathepsin S inhibition. Dihydropyridine 4i represents the first example of an MTDL that combines these biological activities. Full article

One-pot reactions offer advantages like easy automation, higher product yields, minimal waste generation, operational simplicity, and thus reduced cost, time and energy. This review presents a comprehensive overview of one-pot reactions including triethyl orthoformate and amines as valuable and efficient reagents for carrying out two-, three- or four-component organic reactions. Full article

This study presents a novel method for the photocatalytic synthesis of 4-aryl-6-(3-coumarinyl) pyrimidin-2 (1H)-ones (a coumarin derivative) using strawberry dye-sensitized TiO₂ (SD-TiO₂) under visible light. The synthesis of 4-aryl-6-(3-coumarinyl) pyrimidin-2 (1H)-ones was achieved through a three-component, one-pot condensation reaction involving 3-acetyl coumarin, aldehydes, and urea, utilizing SD-TiO₂ as a reusable and innovative photocatalyst at room temperature. The resulting SD-TiO₂ photocatalyst was thoroughly characterized using FT-IR, XPS, XRD, SEM, and BET. The efficacy of SD-TiO₂ was evaluated by comparing it to pristine TiO₂ in terms of photocatalytic activity, and the optimal conditions for the synthesis process were determined. Notably, the SD-TiO₂ photocatalyst exhibited a maximum yield of the compound, reaching up to 96% in just 30 min with a catalyst concentration of 1 mg/mL. This yield surpasses traditional thermal procedures employing reflux conditions, where 1 mg/mL of SD-TiO₂ is sufficient to complete the reaction. The resulting 4-aryl-6-(3-coumarinyl) pyrimidin-2 (1H)-ones were further characterized using ¹H-NMR and ¹³C-NMR. Moreover, the stability of the SD-TiO₂ photocatalyst was confirmed through recyclability experiments and spectroscopic characterization, demonstrating its practicality for up to three consecutive reaction cycles. Full article