Search

Antimicrobial resistance is one of the biggest threats to public health across the globe. Bacteria, fungi, viruses, and protozoans have been exhibiting resistance against antimicrobial drugs making them ineffective. Hence, the development of new antibiotics with a different mode of action is highly desirable. In this study, 10 new chromone‐incorporated fused thiazolo[2,3‐b]quinazolinone derivatives, 8a‐j, have been prepared via Biginelli reaction involving aromatic aldehydes, 1‐tetralone, and thiourea followed by a reaction with 2‐chloro‐N‐phenylacetamide, and Knoevenagel condensation with 3‐formylchromone. All the structures of the compounds were characterized by NMR, FTIR, and mass spectrometry. The in vitro antibacterial activities of all the synthesized compounds against the four different microbial strains were evaluated. Among them, few compounds demonstrated prominent activity against Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa. No appreciable activity of any compound against Klebsiella pneumoniae was observed. Molecular docking studies were employed to reveal the interactions responsible for the potent compounds' activities against S. aureus, S. pyogenes, and P. aeruginosa. Both in vitro and in silico studies have been carried out by using standard agar well diffusion protocol and Auto Dock Vina in PyRx. The results indicated that compound 8c was the potential compound as it showed good affinity toward the receptors of all three organisms. Molecular dynamics simulation of the 8c‐1JIJ complex for 100 ns further confirmed the potentiality of 8c. The pharmacokinetic properties of the compounds indicate that the studied molecules have exhibited a favorable profile. [ABSTRACT FROM AUTHOR]

The syntheses of 3,4-dihydropyrimidin-2(1H)-ones by one-pot, three-component condensation of aldehydes, β-ketoesters and urea or thiourea have been made more simple and efficient by using 20 mol% hydrazine sulfate as catalyst. Aldehydes, β-ketoesters and urea are cyclocondensed in the presence of hydrazine sulfate to produce dihydropyrimidines in ethanol under reflux conditions. The advantages of using hydrazine sulfate as a catalyst over the traditional Biginelli reaction conditions include outstanding yields (80–91%) and a shorter (10–15 hours) reaction time. In order to evaluate the antibacterial efficiencies of the synthesized compounds, we have studied the inhibitions of microbial proliferation of both Gram-positive (Bacillus brevis) and Gram-negative (E. coli) bacterial strains in comparison to a control group. The microbial inhibitions occur in the range of 40–98% by different derivatives of dihydropyrimidinones. Molecular docking studies of the synthesized compounds have also been done using software tools such as SwissADME. [ABSTRACT FROM AUTHOR]

Dihydropyrimidinone skeleton (DHMP) plays a vital part in medicinal and pharmaceutical chemistry as its derivatives exhibit a broad spectrum of anti-microbial, anti-fungal, anti-bacterial, anti-inflammatory and anti-cancer activities. Taking into account the biological significance of DHPMs, organic chemists have developed different methodologies to synthesize these biologically active target molecules. Our review focuses on the one-pot synthesis of dihydropyrimidinones via Biginelli reaction by using the efficient catalysts and reaction conditions, thereby covering the literature published since 2021. [ABSTRACT FROM AUTHOR]

In this work, a series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) were evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. The cytotoxicity of compounds was studied in RAW 264.7 murine macrophage cell line by MTT assay. Then, those with cell viability higher than 70 % were tested for their anti‐inflammatory activity at their non‐toxic doses by evaluating the nitrite level of the cell supernatants with the Griess reagent. Compounds 5 b, 5 d, 5 e, and 5 g demonstrated significant inhibition of nitrite production by 49 %, 59 %, 63 % respectively at 100 μM (p<0.05), whereas 56 % inhibition was seen with 50 μM of 5 g. According to the inhibition of PGE2, compound 5 b showed the most notable effect compared to control. All tested compounds, particularly 5 b, 5 d, 5 e and 5 f reduced the PGE2 level and showed potential analgesic activity. Seven heterocycles 5 a–g showed moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of 5 a–i with COX‐1. Instead, the modelling results also show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2. However, the simulation distinguished the key role of the 2‐OH group in stabilizing the inhibitor‐target complex only in the case of binding to COX‐2. [ABSTRACT FROM AUTHOR]

Chemical reactions and transformations in non‐traditional vessels have gained significant interest in recent years. Flow chemistry, with its advantages in mixing, mass transfer, scalability, and automation, is a driving force behind this paradigm shift. In particular, the Vortex Fluidic Device (VFD) has emerged as a versatile tool across various applications, from organic synthesis to materials science. In this study, the role of the VFD in performing the Biginelli reaction, a multicomponent reaction widely used in pharmaceutical and polymer science, for a post‐polymerization modification is explored. By conducting the Biginelli reaction in the VFD, rapid product formation with low catalyst loading and without the need for high temperatures is achieved. However, the critical need to understand and know solution viscosity, especially within the context of modifying macromolecules is highlighted. [ABSTRACT FROM AUTHOR]

Sulfonated melamine‐formaldehyde (SMF) containing high dispersed TiO2 and ZnO nanoparticles were fabricated into magnetic nanocomposites by two different method material incorporation protocols, including calcination and wet impregnation. Their catalytic performance was investigated toward Biginelli reaction. For the preparation of the first catalyst series, a two‐step protocol was used. Initially, Fe3O4 nanoparticles were coated with SMF (Fe3O4/SMF). Subsequently, they were decorated consecutively with TiO2 (Fe3O4/SMF/TiO2) and ZnO (Fe3O4/SMF/ZnO). The second set of catalysts was prepared using a two‐step process. Fe3O4 nanoparticles were first used to modify SMF (SMF/Fe3O4). Following the initial step, the surface of SMF/Fe3O4 was decorated with both TiO2 (SMF/Fe3O4/TiO2) and ZnO (SMF/Fe3O4/ZnO). To understand the characteristics of the synthesized nanocomposites, a variety of characterization techniques were employed. New catalysts enabled the rapid synthesis (30–45 min) of a range of biologically active 3,4‐dihydropyrimidinones based on the Biginelli reaction with high yields (70–95 % isolated). [ABSTRACT FROM AUTHOR]

The synthesis of 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) was made by utilizing newly synthesized heterogeneous mixed ligand-based Ni-phen MCM-41 catalyst with variety of aryl aldehydes (viz. electron donating, electron withdrawing, fused, disubstituted and unsaturated substituents), ethylacetoacetate, urea and ethanol as a solvent by using two different energy sources: conventional and ultrasonication methods. The effectiveness of the two methods was compared and found that the formation of Biginelli products in ultrasonication method (65–92% yield at 60 °C, 45 min) is better than the conventional method (63–90% yield at 78 °C, 2 h) by yield, temperature and time of the reaction. The formation, heterogeneous nature and morphology of the catalyst have been characterized by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma-optical emission spectrometry (ICP-OES), thermogravimetric analysis (TGA) and N2 adsorption–desorption isotherm (BET) techniques. Moreover, the catalyst was recoverable, reusable and very much efficient for three consecutive runs without any significant loss of its catalytic activity. The heterogeneity nature of the recovered catalyst was checked by hot filtration test. [ABSTRACT FROM AUTHOR]

In this study, we introduce a novel porous metal–organic framework named Co2(bbda)2(DMF)2·5H2O, or MOF‐UoR‐1, synthesized via hydrothermal techniques employing a unique Schiff base ligand. The framework underwent comprehensive characterization, confirming its microporous nature through gas‐sorption measurements. MOF‐UoR‐1 demonstrated remarkable efficacy as a catalyst for the one‐step synthesis of pyrimidine analogs. Structural validation of the synthesized pyrimidines was accomplished via 1H‐nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) analyses. Through systematic experimentation, the optimal catalyst dosage (40 mg) was determined, showcasing its effectiveness across various aldehydes, 1,3‐carbonyl compounds, and urea substrates. Noteworthy is the broad applicability of this environmentally friendly protocol, which offers advantages such as high yields (96%), rapid reaction times (90 min), straightforward product isolation, and product purity without necessitating column chromatography. Furthermore, the catalytic integrity of the framework remained intact, enabling its reuse without compromising performance. This research presents a promising approach for the synthesis of pyrimidine derivatives, with significant implications for sustainable and efficient chemical synthesis methodologies. [ABSTRACT FROM AUTHOR]

Copyright of Biomass Chemical Engineering is the property of Editorial Office of Biomass Chemical Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The relevance of the asymmetric Biginelli reaction (ABR) has been increased in this century, due to the pharmacological application of its products. This review focuses predominantly on articles published in the period from 2015 to 2024 on asymmetric synthetic advances in the formation of dihydropyrimidinones (DHPMs), dihydropyrimidinethiones (DHPMTs), and related compounds. The relevant bibliography on general processes in the Biginelli reaction and some methods of separation of isomers have also been referenced. [ABSTRACT FROM AUTHOR]

New 2-(4-carboxyphenylhydrazinylidene)[1,3]thiazolo[3,2-a]pyrimidine derivatives were synthesized in high yields by the reactions of 5-aryl-6-ethoxycarbonyl-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine with 4-carboxyphenyldiazonium chloride. The azo coupling occurs at the 2 position of the substrate. Different types of intra- and intermolecular non-covalent interactions can affect the supramolecular assembly of the molecules in the crystal structures and the molecular configuration of the synthesized compounds. The combined contribution of supramolecular non-covalent interactions leads to several types of the self-assembly in the crystalline phase, such as hydrogen-, chalcogen-, and π—π-bonded racemic dimers. In the case of compounds containing the m-chlorophenyl substituent at the C(5) position of the thiazolo[3,2-a]-pyrimidine scaffold, these interactions lead to the formation of halogen-bonded homochiral chains. Due to the π—π stacking between the electron-rich thiazolopyrimidine scaffold and the electron-deficient carboxyphenyl moiety, there occurs the formation of dense layers in the solid phase when selecting the appropriate substituents at the C(5) atom. The crystallization conditions (vapor diffusion and slow evaporation) were found to influence the configuration of the C=N-arylhydrazone moiety. [ABSTRACT FROM AUTHOR]

A novel composite, CoFe-LDH/ZIF-67 is designed and fabricated via an easy approach in two steps and its identification was followed by various analyses such as FT-IR, XRD, SEM, TEM, EDS, BET and STA. The CoFe-LDH/ZIF-67 was constructed by the growth of ZIF-67 on CoFe-LDH surface. The composite CoFe-LDH/ZIF-67 powerfully catalyzed the formation of dihydropyrimidinone derivatives via the Biginelli reaction in the absence of solvent. CoFe-LDH/ZIF-67 has significant catalytic activity, which was predominantly accredited to the great surface area and the synergy of CoFe-LDH and ZIF-67. Furthermore, LDH/ZIF-67 has revealed recyclability for five runs with a slight decrease in the yield. [ABSTRACT FROM AUTHOR]

Various bi- and polycyclic pyrimidine derivatives (including fused ones) containing different aza- and carbocyclic fragments have been synthesized via a modified Biginelli reaction. [ABSTRACT FROM AUTHOR]

Lewis acid heterogeneous catalyst, ZnAl2O4/SiO2 nanocomposite, was determined as a strong catalyst for the green and safe three-component reactions by the one-pot procedure. The effect of factors, such as the amount of catalyst, the molar ratio of reactants, reflux time and temperature on the three-component reactions were investigated. Also, the parameters of green chemistry were studied. These reactions under solvent-free conditions in the presence of ZnAl2O4/SiO2 dramatically increased the yield of the formation of dihydropyrimidinones derivatives in a very short time. The results showed that ZnAl2O4/SiO2 under solvent-free conditions greatly accelerate the three-component reactions with the advance of imine pathway and preventing the formation of unwanted side-products. Also, aromatic aldehydes with low electron density had the best outcomes. Lower reaction yield was produced by β-ketoesters with more steric hindrance. Without noticeably altering reaction time or yield, this catalyst employed six times. The technique is environmentally friendly, as shown by its low E-factor of 0.218–0.570 and high atom economy of 90.025–87.237. [ABSTRACT FROM AUTHOR]

The paper describes the construction of a new series of pyrimidinone-linked thiazole derivatives through bromination of the initial Biginelli reaction product followed by the Hantzsch thiazole synthesis route. Various analytical techniques, including FT-IR, 1H NMR, 13C NMR, and LCMS analysis, were employed to confirm the formation of the products. The synthesized compounds were primarily evaluated for their antibacterial activity, with a specific focus on their IC50 values. Compound 4c demonstrated the most potent efficacy, displaying MIC and MBC values that varied from 0.23 to 0.71 mg/mL and 0.46–0.95 mg/mL, respectively. The anti-inflammatory potential was also observed in analogs 4a and 4c with marked activity in the 33.2–82.9 μM concentration range. Moreover, compounds 4a, and 4c demonstrated strong antioxidant effects, as reflected by their excellent IC50 values of 38.6–43.5 μM respectively. DFT investigation showed that B. cereus was more susceptible, and E. coli was more resistant, with chloro-substituted compounds exhibiting potential reactivity. Some molecules with chloro-substituents showed promising results in density functional theory when compared to other substituents. In addition, the molecules underwent a corrosion study and demonstrated a high level of inhibition efficiency (4c) in comparison to other molecules. Further in silico studies of the synthesized thiazoles confirmed the good interactions with the target.

The Biginelli reaction synthesizes dihydropyrimidones through a multi-component reaction. A β-ketoester, aldehyde, and urea or thiourea react in the presence of an acid catalyst to form these dihydropyrimidones. 3,4-Dihydropyrimidin-2(1H)-One/Chromone/Triazole hybrids (9a-9l) were synthesized by multiple steps including one pot Biginelli multicomponent reaction depicted in the scheme. An efficient method for the Biginelli reaction of Chromone aldehyde, acetoacetate esters, and urea employed in the presence of ferric chloride is described. In the end, we have successfully synthesized twelve derivatives of 3,4-Dihydropyrimidin-2(1H)-One/Chromone/Triazole hybrids and subjected them to testing for Antibacterial activity and α-glucosidase inhibition activity. Among these derivatives, compound 9g (IC50 = 142.92 nmol) and 9e (144.49 nmol) exhibited significant inhibitory activity in comparison to the positive control acarbose (IC50 = 350.91 nmol). Compound 9g demonstrated the most significant suppression against Escherichia coli and Bacillus cereus, with zone diameters of 8.8 ± 1.35 mm and 9.1 ± 0.23 mm, respectively. Compound 9b displayed a clear area where bacterial growth was inhibited, measuring 7.5 ± 1.25 mm against Klebsiella pneumonia. Compound 9k exhibited a zone of inhibition measuring 8 ± 1.2 mm in radius against Staphylococcus epidermidis. The docking results for the synthesized compounds indicate that compound 9b exhibited the most favorable docking score of −10 kcal/mol, whereas compound 9a had the second-best docking score of −8.7 kcal/mol. Molecular docking was utilized to examine the interactions between the title compounds and α-glucosidase, in order to provide valuable insights. The data obtained revealed significant interactions that contribute to the inhibitory effects of the drugs against α-glucosidase. These compounds exhibit significant potential as attractive initial candidates for the development of new α-glucosidase inhibitors.

An innovative and environmentally sustainable approach is presented for the synthesis of cadmium oxide nanoparticles (CdONPs), leveraging the leaf extract of the pigeon pea plant (Cajanus cajan) as both reductive and capping agents. This environmentally friendly heterogeneous CdONPs was meticulously characterized through FT‐IR, PXRD, HR‐TEM, SEM‐EDAX, XPS and UV‐Vis spectroscopic analyses. These NPs were subsequently applied to facilitate the three‐component Biginelli reaction using ethyl acetoacetate, urea, and substituted benzaldehydes for producing dihydropyrimidone derivatives in good to excellent yield. The methodology was tested for different aldehydes containing electron‐withdrawing and electron‐donating groups. The catalyst demonstrated consistent performance over approximately five cycles, exhibiting negligible loss in yield and catalytic potential. The proposed mechanistic pathway of the reaction was elucidated through intermediate mass analysis and further validated by Density Functional Theory (DFT) calculations and catalytic surface adsorption studies. [ABSTRACT FROM AUTHOR]

Nowadays, emerging nanocatalysts have gained much attention in the field of organic transformations for the development of greener chemistry protocols. Also, the Biginelli reaction has gained prominence amidst multicomponent reactions due to the extensive therapeutic significance of the product dihydropyrimidinones (DHPMs). In this work, first-time zinc chromite nanoparticles (ZnCr2O4 NPs) were prepared using cow urine (CoU) as a natural source through a biogenic approach. The physicochemical traits of the synthesized ZnCr2O4 NPs were investigated via XRD, UV-DRS, IR, FESEM, EDX, HRTEM, and XPS techniques. Furthermore, ZnCr2O4 NPs were implemented as a heterogeneous nanocatalyst for sustainable, uncomplicated, and one-pot synthesis of DHPM analogs. The synthetic strategy offers diverse appealing attributes, such as simplicity, bland reaction systems, facile work-up, reusability of catalyst, and excellent yield. Being heterogeneous, the nanocatalyst was simply retrieved after the reaction and reused (up to 5 cycles) in the Biginelli reaction without any noticeable diminishment in catalytic performance. As a result, the current study reveals that creating ZnCr2O4 NPs through a simple green approach and evaluating excellent catalytic activity may aid nanochemistry research by opening up new pathways for advanced organic transformations. [ABSTRACT FROM AUTHOR]

This research work focuses on the potential usefulness of iron ion-exchanged Indian bentonite for one-pot synthesis of 3,4-dihydropyrimidine-2(1H)-thiones. Our goal was to produce mesoporous Fe3+-exchanged Indian clay (Fe3+-ExIC) and its supported forms through a wet impregnation technique. The physicochemical properties of the catalysts, such as XRD, FTIR, TGA, physisorption studies, SEM, and acidity, were investigated. It was found that Fe3+-ExIC catalysts are efficient and reusable acidic heterogeneous catalysts for the synthesis of 3,4-dihydropyrimidine-2(1H)-thiones by refluxing aldehyde, methyl acetoacetate and thiourea with acetonitrile in cyclocondensation. An optimized reaction condition was found for preparing 5-methoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-thione. A possible mechanism for the synthesis of 3,4-dihydropyrimidine-2(1H)-thiones has been proposed. Melting point, FTIR, and proton NMR were used to identify the products. Adequate catalyst activity was maintained over a period of six cycles, and a reduction in activity was attributed to a decrease in the acidity of the recycled catalyst. [ABSTRACT FROM AUTHOR]

This study demonstrates the successful synthesis of sulfosalicylic acid-functionalized silica-coated magnetic nanoparticles, referred to as MNPs-SSA, as a reusable heterogeneous acid catalyst through a straightforward process. The material structures were thoroughly validated using a diverse set of spectroscopic, microscopic, and magnetic techniques, such as FT-IR, EDX, XRD, FE-SEM, TEM, TGA, and VSM, ensuring comprehensive examination and confirmation. The catalytic efficiency of this innovative material was evaluated using the one-pot, three-component Biginelli reaction under solvent-free conditions. The enhanced reaction conditions described here facilitate the synthesis of a wide variety of substituted dihydropyrimidinones, resulting in high purity and excellent yields in a short reaction time. Furthermore, the catalyst exhibited remarkable thermal stability and could be easily recovered from the reaction mixture using an external magnetic field, enabling multiple consecutive uses without a significant decrease in its catalytic efficiency. [ABSTRACT FROM AUTHOR]

Signaling proteins involved in the TGF-β (transforming growth factor beta) pathway regulate cellular processes such as cell growth, division, differentiation, migration, invasion, and apoptosis. Due to the large contribution of the TGB-β signaling pathway to carcinogenesis, these proteins are promising oncotargets. Based on the literature data, we propose a new structural type of TGF-β receptor inhibitors that are 2-amino-pyrimidine derivatives. Two general approaches to their synthesis have been proposed, where the key step is the three-component Biginelli condensation producing the pyrimidine fragment. Sixteen new compounds have been synthesized, and their in vitro antiproliferative activity has been evaluated against a panel of tumor cell lines. [ABSTRACT FROM AUTHOR]

A facile and efficient protocol for one-pot three-component synthesis of a series of novel 4-substituted-2-thioxo-3,4-dihydro-1H-pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5(2H)-one derivatives has been developed. Compounds were synthesized by the reaction of 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-dione, various aromatic aldehydes, and thiourea using Iodine as catalyst in acidic medium. The synthesized compounds obtained in good to excellent yields (52–83%) with improved reaction time and chloro substituent at four-position yielded the product in excellent quantity (83%). The synthesized compounds have been characterized by 1H, and 13C NMR, IR, and mass spectral analysis, and screened for their in vitro antibacterial activity against Bacillus subtilis, Salmonella typhemurium, Escherichia. coli, and Staphylococcus aureus using disk diffusion method. Biological screening revealed that the newly synthesized compounds exhibit interesting activities against several bacterial strains. Among all the synthesized compounds, the in vitro antibacterial activity displayed by compound 6j was highest against S. typhemurium with ZOI 23.5. mm (MIC = 3.125 µg/mL). Docking studies further supported the findings, and provided for the basis of linkages in terms of conventional hydrogen bonds, and pi- bonding patterns. In nutshell, the present study thus paved the way for developing lead compounds which could be potentially used as an efficient antibacterial drug in humans after appropriate animal, and clinical trials. [ABSTRACT FROM AUTHOR]

ZPD is a type of metal–organic framework based on zinc ions. Its structure contains 2,5 pyridine dicarboxylic acid as ligand, and it was synthesized by the hydrothermal method. Its metal–organic framework has a high surface area, suitable micropores, and a very regular crystalline structure. In this study, Biginelli reaction and chromene synthesis were realized using Cu@ZPD as a catalyst. The prepared products were obtained with high-to-excellent yield (80–96%). The mentioned catalyst was identified by Fourier transform infrared (FT-IR), Brunauer–Emmett–Teller (BET), thermogravimetric analysis (TGA), X-ray diffraction (XRD), field emission–scanning electron microscopy (FE-SEM), energy-dispersive X-ray (EDX) mapping, transmission electron microscopy (TEM), and inductively coupled plasma optical emission spectroscopy (ICP-OES) analyses. By using ICP-OES, Cu loading was detected at nearly 3 wt%. The prepared catalyst can be reused 6 times without significantly losing its catalytic activity. Also, 1HNMR, 13CNMR, and FT-IR spectroscopy was used to identify the products. [ABSTRACT FROM AUTHOR]

The syntheses of pyrimidinone derivatives by the Biginelli reaction in N-methylpyridinium methyl sulfate [mPyrMeSO4] as an ionic liquid medium have been reported. This protocol provides a highly efficient and selective route for the synthesis of structurally diverse pyrimidinones under milder reaction conditions. The proposed conditions tolerate differently substituted aldehydes and ketones and afford products in synthetically useful yields. Furthermore, camphor, benzil, benzoin, and ethyl acetoacetate were utilized for the Biginelli reaction for the first time, and the resulting pyrimidinones were obtained in excellent yields. [ABSTRACT FROM AUTHOR]

The technological trend toward "Wealth from Waste" is pertinent with the effective utilization of agricultural waste such as rice husk with properties such as availability, cost-effectiveness, durability, biodegradability, and environmentally friendly resources. In this article, nanodiopside concerning their wide application was synthesized using silica source from rice husk, calcium nitrate, and magnesium chloride. In this study, diopside nanoparticle was synthesized using rice husk ash obtained from agricultural waste. Then, the structure of nanodiopside was corroborated using FT-IR, EDX, TGA, FE-SEM, BET, XRD spectroscopic methods and the antibacterial properties of nanodiopside as well as its use as a nanocatalyst in Biginelli reaction and adsorbent to remove congo red dye was investigated. The experiment design method was used to optimize the Biginelli reaction conditions and to remove congo red dye. Finally, the antibacterial properties of nanodiopside were investigated. The results show that the heterogeneous diopside nanocatalyst can be reused up to 5 times. In addition to being economically and environmentally green and having good performance, nanodiopside reduces reaction time and the product has a good yield. In addition, recovery of the adsorbent shows that nanodiopside can be reused up to 4 times. Also, the study of adsorption isotherm and adsorption kinetics in optimal conditions showed that they correspond to the Langmuir and pseudo-second-order models, respectively. Furthermore, the data showed that nanodiopside has antibacterial properties. [ABSTRACT FROM AUTHOR]

A novel approach for the ultrasound-assisted synthesis of 3,4‑dihydropyrimidin‑2(1H)‑ones was developed by using biodegradable supported nanoparticles in a hydrotropic aqueous medium. Agar-supported NiO nanoparticles (NiO@AG NPs) were synthesized by in-situ co-precipitation method and characterization by means of spectroscopic and microscopic techniques indicates that spherical NiO NPs successfully supported on the surface of agar with particle size 31.22 nm containing Carbon, Nickel and Oxygen as major elements. NiO@AG NPs exhibit higher activity for the synthesis of 3,4‑dihydropyrimidin‑2(1H)‑ones in an aqueous medium by using hydrotropes with high (463.51 h−1) turn over frequency. Short reaction time, high efficiency, centrifugation-free method of separation of the catalyst, and column chromatography-free isolation of the product are the key factor of this protocol. The easy synthetic method and stable form of NiO nanoparticles supported on agar suggest that it could be an efficient material for water-based organic transformation on a large scale with high turnover frequency in the future. [ABSTRACT FROM AUTHOR]

A rapid and enormously professional new-flanged 3,5-disubstituted triazole derivatives were synthesized by the one-pot five-component condensation reaction in the course of transesterification followed by the Biginelli/Click reaction in aqueous medium using magnetic CuFe2O4 NPs as heterogeneous catalyst beneath ultrasonic acceleration in aqueous medium. The synthesized 3,5-disubstituted triazole derivatives were finely characterized and the characterized desired target molecules were employed for the quantum chemical calculations for each reactant and product have been well thought-out using density functional theory. Furthermore, the molecular docking and ADMET revision of all the derivatives have been achieved as digestive enzyme and Cathepsin-B inhibitors and their connections with BSA to treat different diseases. [ABSTRACT FROM AUTHOR]

TUD-1, a novel sponge-like three-dimensional mesoporous silica material, was synthesized in one-step using a hydrothermal technique and triethanolamine as a template. To enhance its acidic properties, the TUD-1 material underwent sulfonation with varying amounts of sulfonic groups (1 and 3 wt%). Structural characteristics were determined using XRD, FTIR, Raman, BET analysis, HRTEM, SEM, and XPS. Surface acidities of the catalysts were evaluated through non-aqueous potentiometric titration and FTIR analysis of chemisorbed pyridine. The performance of catalysts was assessed in various reactions, including the Pechmann reaction, Friedel-Crafts acylation reaction, and Biginelli reaction for synthesis of 7-hydroxy-4-methyl-2H-chromen-2-one, aromatic ketones and 3, 4-dihydropyrimidin-2(1H)-one. The findings confirm that the TUD-1 mesoporous structure did not undergo any significant alteration post sulfonation. The sulfonated catalysts exhibited higher surface acidities than TUD-1. A correlation between surface acidity, particularly Brönsted acid sites, and catalytic efficiency in selected reactions was evident from both catalytic testing and characterization. Under moderate conditions, TUD-1-3SO3H exhibited outstanding catalytic performance and remarkable reusability across all selected reactions.

Multicomponent reactions involving three or more reactants are commonly used to prepare dihydropyrimidinone with various bioactivities. This study reports the different routes for the synthesis of benzaldehyde-based dihydropyrimidinone via the Biginelli reaction and investigates the yield of the obtained products. The synthesis was performed via routes A, B, C, D, and E based on the formation of iminium, enamine, and Knoevenagel intermediates between urea, benzaldehyde, and ethyl acetoacetate. Route A, through a one-pot reaction via iminium, produced dihydropyrimidinone with a yield of 58%. The product from route B via iminium was obtained in 62% yield. Route C and D occurred via enamine at room temperature, and reflux gave the product 31% and 40% yield, respectively. Route E involving Knoevenagel intermediate provided the product in a 38% yield. 1H NMR, FTIR, and MS spectroscopic techniques were used for structure elucidation.

A novel method has been developed to use ammonium tetrafluoroborate (NH4BF4) directly as catalyst in Biginelli reaction. A new paradigm of the Biginelli reaction for the synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones derivatives found the use of ammonium tetrafluoroborate as a novel, inexpensive, readily available, non‐toxic and mild catalyst in good to excellent yields. Notably, this is the first time that ammonium tetrafluoroborate is directly used as a catalyst in organic synthesis. So far, no organic reaction is available in literature where NH4BF4 is directly used as catalyst. However, some reactions are found where NH4BF4 is used with other catalysts as promoters or additives. The protocol developed has several advantages, such as highly efficient, simple, atom‐economical, environmentally friendly, easy synthetic and purification methods. [ABSTRACT FROM AUTHOR]

New tetrahydropyrimidone derivatives with structural modifications of anti-cancer drug, monastrol, were synthesized, and molecular docking study of the interaction with epidermal growth factor receptor tyrosine kinase (EGFR-TK) was performed. The substituted aromatic part was derived from benzaldehyde derivatives having hydroxy, methoxy and fluoro substituents at 3,4,5 positions. Structural modifications in monastrol with conversion of methyl group to trifluoromethyl fraction and the sulphur atom in place of oxygen atom are the core of synthesis in this paper. Structural and bonding features of newly synthesized compounds are reported along with molecular docking study with EGFR-TK in comparison to monastrol. Target compounds were synthesized using p-toluenesulfonic acid as catalyst. Synthesized compounds show improved binding affinity as compared to monastrol in docking study. ADMET study of all the compounds shows high GI absorption. Single-crystal X-ray study of four derivatives with superposition of the crystal structures is also reported in the study. [ABSTRACT FROM AUTHOR]

(2E)-3-(Dimethylamino)-1-(2,4,5-trimethoxyphenyl)prop-2-en-1-one was obtained by the reaction of 2,4,5-trimethoxyacetophenone with N,N-dimethylformamide dimethyl acetal (DMF-DMA) by refluxing without a solvent for 12 h. The resulting enaminone was reacted with substituted benzaldehydes, thiourea in glacial acetic acid which acted as a catalyst to afford novel dihydropyridine-2(1H)-thione derivatives 3a–3j in good yield. Spectroscopic methods like FT-IR, 1H NMR, 13C NMR, and GC/MS and elemental analysis were employed to confirm and characterize the structures of all newly synthesized compounds. The density functional theory (DFT) analysis with a hybrid correlation functional (B3LYP) and 6-311++G(d,p) basis set was used to optimize the geometry of the synthesized compounds. The charge transfer in their molecules was analyzed by calculations of the HOMO and LUMO energies. The molecular docking study demonstrated that dihydropyridine-2(1H)-thione derivatives 3a–3j bind well to the multidrug transporter ABCG2 via interactions comparable to the native co-crystallized inhibitor MZ29. All compounds of the series were tested for antimicrobial activity and were found to be active against different Gram-positive and Gram-negative bacterial, as well as fungal strains. Compound 3j containing a 3,4-dimethoxyphenyl substituent showed the most promising activity against all the tested strains. [ABSTRACT FROM AUTHOR]

Multicomponent reactions involving three or more reactants are commonly used to prepare dihydropyrimidinone with various bioactivities. This study reports the different routes for the synthesis of benzaldehyde-based dihydropyrimidinone via the Biginelli reaction and investigates the yield of the obtained products. The synthesis was performed via routes A, B, C, D, and E based on the formation of iminium, enamine, and Knoevenagel intermediates between urea, benzaldehyde, and ethyl acetoacetate. Route A, through a one-pot reaction via iminium, produced dihydropyrimidinone with a yield of 58%. The product from route B via iminium was obtained in 62% yield. Route C and D occurred via enamine at room temperature, and reflux gave the product 31% and 40% yield, respectively. Route E involving Knoevenagel intermediate provided the product in a 38% yield. ¹H NMR, FTIR, and MS spectroscopic techniques were used for structure elucidation. [ABSTRACT FROM AUTHOR]

Antagonists of the A2B adenosine receptor have recently emerged as targeted anticancer agents and immune checkpoint inhibitors within the realm of cancer immunotherapy. This study presents a comprehensive evaluation of novel Biginelli-assembled pyrimidine chemotypes, including mono-, bi-, and tricyclic derivatives, as A2BAR antagonists. We conducted a comprehensive examination of the adenosinergic profile (both binding and functional) of a large compound library consisting of 168 compounds. This approach unveiled original lead compounds and enabled the identification of novel structure-activity relationship (SAR) trends, which were supported by extensive computational studies, including quantum mechanical calculations and free energy perturbation (FEP) analysis. In total, 25 molecules showed attractive affinity (Ki < 100 nM) and outstanding selectivity for A2BAR. From these, five molecules corresponding to the new benzothiazole scaffold were below the Ki < 10 nM threshold, in addition to a novel dual A2A/A2B antagonist. The most potent compounds, and the dual antagonist, showed enantiospecific recognition in the A2BAR. Two A2BAR selective antagonists and the dual A2AAR/A2BAR antagonist reported in this study were assessed for their impact on colorectal cancer cell lines. The results revealed a significant and dose-dependent reduction in cell proliferation. Notably, the A2BAR antagonists exhibited remarkable specificity, as they did not impede the proliferation of non-tumoral cell lines. These findings support the efficacy and potential that A2BAR antagonists as valuable candidates for cancer therapy, but also that they can effectively complement strategies involving A2AAR antagonism in the context of immune checkpoint inhibition.

A series of 3,4-dihydropyrimidine-2-one derivatives were designed and synthesized as monastrol analogs by Biginelli cyclocondensation of a β-keto compounds and aromatic aldehyde with urea or thiourea. Biginelli cyclocondensation usually produces racemic mixtures of 3,4-dihydropyrimidine-2-ones. Enantiomers of 3,4-dihydropyrimidine-2-ones (R and S) often show different biological activities and may even have an opposite action profile. Therefore, developing of the stereoselective synthesis of 3,4-dihydropyrimidine-2-ones is one of the priorities of medicinal chemistry. Following observed diverse pharmacological effects of monastrol, 3,4-dihydropyrimidine-2-ones as new anti-cancer agents are the pharmacological category which improve and decrease the side effects of dihydropyrimidines especially resistance to chemotherapeutic drugs. 3,4-Dihydropyrimidine-2-ones followed their anticancer effects by inhibiting the kinesin motor protein. Because of the specific function of these proteins in mitosis, targeting the Kinesin spindle protein (KSP, or Eg5) as the most dramatic target of the mitotic kinesin family open up an opportunity for the progress of more selective antimitotics with an improved side effect profile. These facts prompted us to investigate if the effects of inhibitory enantiomers (R and S) of 3,4-dihydropyrimidine-2-ones could possibly differ from each other. Therefore, molecular docking of both R and S stereoisomers of 3,4-dihydropyrimidine-2-ones and monastrol was performed to study the interaction between inhibitors and the kinesin spindle protein binding site. According to docking studies, S stereoisomer of D2 (SD2) has the best score among the synthesized compounds and shows probably more stable binding with the active site of the enzyme and can be considered as a candidate for biological evaluation.

The relevance of the asymmetric Biginelli reaction (ABR) has been increased in this century, due to the pharmacological application of its products. This review focuses predominantly on articles published in the period from 2015 to 2024 on asymmetric synthetic advances in the formation of dihydropyrimidinones (DHPMs), dihydropyrimidinethiones (DHPMTs), and related compounds. The relevant bibliography on general processes in the Biginelli reaction and some methods of separation of isomers have also been referenced.

This article describes the synthesis of iron oxide/hydroxyapatite (Fe3O4/HAp) nanocomposite by the hydrothermal method and utilization of Fe3O4/HAp as a competent, reusable, magnetically separable nano-composite catalyst for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives by cyclo-condensation of dicarbonyl compound, aryl-aldehydes and (thio)urea in EtOH:H2O (1:1, v/v) as an eco-safe solvent. The Fe3O4/HAp nano-catalyst was characterized by spectral and analytical techniques such as FT-IR, SEM, XRD, EDX and VSM. The advantage of this procedure includes excellent product yield in a shorter time, a simple workup procedure, reusability of the catalyst, and avoidance of volatile organic solvent, and strong mineral acid. [ABSTRACT FROM AUTHOR]

The sulfonation of a partly carbonized litchi shell with concentrated H2SO4 afforded a carbon solid acid catalyst. Various physicochemical techniques, such as XRD, X-ray photoelectron spectroscopy, FT-IR spectroscopy, scanning electron microscopy (SEM), and N2 physisorption measurements were used to study the structural properties of the prepared materials. It was an amorphous carbon material composed of aromatic carbon in random orientations. The catalytic behavior of the material was examined in the di-carbonyl compounds and urea with aromatic aldehydes for 3,4-dihydropyridine-2 (1H)-ones (DHPMs) production. Sulfonic acid groups were present on the surface at a density of 0.82 mmol/g, which led to a high DHPMs conversion efficiency of 95% at SO3H-CL at 80 °C after 3.5 h. More importantly, SO3H-CL has satisfying recyclable features and could maintain an 83% yield of its initial catalytic activity in the 6th catalytic run. [ABSTRACT FROM AUTHOR]

A new series of 6-methyl-4-aryl-2-thio-1,2,3,4-tetrahydropyrimidine-5-carboxylic acids ethyl esters was synthesized. The reaction of the obtained esters with dimethyl 2-chloroethynylphosphonate leads to the selective formation of new ethyl 3-(dimethoxyphosphoryl)-5-aryl-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylates. [ABSTRACT FROM AUTHOR]

A series of 3,4-dihydropyrimidine-2-one derivatives were designed and synthesized as monastrol analogs by Biginelli cyclocondensation of a β-keto compounds and aromatic aldehyde with urea or thiourea. Biginelli cyclocondensation usually produces racemic mixtures of 3,4-dihydropyrimidine-2-ones. Enantiomers of 3,4-dihydropyrimidine-2-ones (R and S) often show different biological activities and may even have an opposite action profile. Therefore, developing of the stereoselective synthesis of 3,4-dihydropyrimidine-2-ones is one of the priorities of medicinal chemistry. Following observed diverse pharmacological effects of monastrol, 3,4-dihydropyrimidine-2-ones as new anti-cancer agents are the pharmacological category which improve and decrease the side effects of dihydropyrimidines especially resistance to chemotherapeutic drugs. 3,4-Dihydropyrimidine-2-ones followed their anticancer effects by inhibiting the kinesin motor protein. Because of the specific function of these proteins in mitosis, targeting the Kinesin spindle protein (KSP, or Eg5) as the most dramatic target of the mitotic kinesin family open up an opportunity for the progress of more selective antimitotics with an improved side effect profile. These facts prompted us to investigate if the effects of inhibitory enantiomers (R and S) of 3,4-dihydropyrimidine-2-ones could possibly differ from each other. Therefore, molecular docking of both R and S stereoisomers of 3,4-dihydropyrimidine-2-ones and monastrol was performed to study the interaction between inhibitors and the kinesin spindle protein binding site. According to docking studies, S stereoisomer of D2 (SD2) has the best score among the synthesized compounds and shows probably more stable binding with the active site of the enzyme and can be considered as a candidate for biological evaluation. [ABSTRACT FROM AUTHOR]

3,4‐Dihydropyrimidin‐2(1H)‐ones (DHPMs) and 1,4‐dihydropyridines (DHPs) are well‐established classes of heterocyclic compounds with remarkable biological properties. Various protonated organic amines were screened as Brønsted acidic ionic liquid catalysts under the Biginelli and Hantzsch reaction conditions for synthesizing novel DHPMs and DHPs, respectively, starting from biorenewable furfurals. 1,4‐Diazabicyclo[2.2.2]octanium diacetate (DABCO‐DA) was found as an efficient catalyst for the organic solvent‐free synthesis of novel DHPMs and DHPs in excellent (>85 %) isolated yields. The process parameters (e. g., temperature, molar ratio of reagents, duration, and loading of acid catalyst) were optimized, and a general synthetic protocol for synthesizing DHPMs and DHPs from 5‐substituted‐2‐furaldehydes has been developed. The DABCO‐DA catalyst was successfully recovered from the reaction mixture and reused for four consecutive cycles. [ABSTRACT FROM AUTHOR]

In this work, a new heterogeneous catalyst based on 1,2,3‐triazole complex of copper supported on core–shell Fe3O4@SiO2 nanoparticles was designed and characterized by using several methods such as infrared spectroscopy (FTIR), X‐ray diffraction (XRD), thermogravimetry analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy‐dispersive X‐ray spectroscopy (EDX). The magnetic nanocatalyst was successfully employed for the synthesis of different functionalized 3,4‐dihydropyrimidin‐2(1H)‐ones/thiones by a one‐pot multicomponent condensation reaction under solvent‐free conditions. Among the advantages of the developed catalytic protocol are the high yields, short reaction times, ecofriendly, easy workup and purification conditions. [ABSTRACT FROM AUTHOR]

2-Methylsulfanyl-1,4-dihydropyrimidine derivatives were synthesized by alkylation of 1,2,3,4-tetrahydropyrimidines with methyl iodide in the presence of pyridine. Their structures were confirmed by spectrometric charachterisation. In silico ADME and physicochemical properties are calculated using swissADME software. All compounds tested for analgesic activity by acetic acid-induced writhing method. The compounds ethyl 4-(4-ethenylphenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate (IIh) and ethyl 2-(methylsulfanyl)-4-[4-(propan-2-yl)phenyl]-1,4-dihydropyrimidine-5-carboxylate (IIl) exhibited maximum analgesic activity. Compounds methyl 4-(3-chlorophenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate, ethyl 4-(3-chlorophenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate, methyl 4-(4-ethenylphenyl)-2-(methylsulfanyl)-1,4-dihydropyrimidine-5-carboxylate and methyl 2-(methylsulfanyl)-4-[4-(propan-2-yl)phenyl]-1,4-dihydropyrimidine-5-carboxylate showed good activity. The remaining compounds showed moderate analgesic activity. In vitro cyclooxygenase, COX-2 inhibition assay performed using COX 2 (human) inhibitor screening assay kit. Title compounds exhibited inhibitory activity against COX-2 (IC50 = 0.66–0.87 µM). [ABSTRACT FROM AUTHOR]

In this study, we present the highly efficient and rapid synthesis of substituted dihydropyrimidinone derivatives through an ultrasound-accelerated approach. We utilize copper ferrite (CuFe2O4) magnetic nanoparticles as heterogeneous catalysts, employing the well-known Biginelli reaction, under solvent-free conditions. The impact of the solvent, catalyst amount, and catalyst type on the reaction performance is thoroughly investigated. Our method offers several notable advantages, including facile catalyst separation, catalyst reusability for up to three cycles with the minimal loss of activity, a straightforward procedure, mild reaction conditions, and impressive yields, ranging from 79% to 95%, within short reaction times of 20 to 40 min. Furthermore, in the context of fighting COVID-19, we explore the potential of substituted dihydropyrimidinone derivatives as inhibitors of three crucial SARS-CoV-2 proteins. These proteins, glycoproteins, and proteases play pivotal roles in the entry, replication, and spread of the virus. Peptides and antiviral drugs targeting these proteins hold great promise in the development of effective treatments. Through theoretical molecular docking studies, we compare the binding properties of the synthesized dihydropyrimidinone derivatives with the widely used hydroxychloroquine molecule as a reference. Our findings reveal that some of the tested molecules exhibit superior binding characteristics compared to hydroxychloroquine, while others demonstrate comparable results. These results highlight the potential of our synthesized derivatives as effective inhibitors in the fight against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The interaction employing sulfamide and enolizable ketones was closely inspected in Biginelli reaction. The three-component variation of the reaction ''sulfamide + ketone + anisaldehyde'' and ''sulfamide + ketone + N,N-diethylacetoacetamide'' featured a lack of selectivity and provided a mixture of possible condensation products. Selectivity was improved when ketones were used in the reaction both as carbonyl and enol components. It was shown that trimethylsilyl chloride promoted interaction of sulfamide with ketones to afford 1,2,6- thiadiazines. Limitations were noted and unpredictable outcomes of the reaction were discussed as well. [ABSTRACT FROM AUTHOR]

Copyright of Experimental Technology & Management is the property of Experimental Technology & Management Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)