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5H-Chromeno[2,3-b]pyridines are important compounds with industrial, biological, and medicinal properties. In this short note, the multicomponent reaction of salicylaldehyde, malononitrile dimer, and 2-phenyl-5-(trifluoromethyl)-2,4-dihydro-3H-pyrazol-3-one in dimethyl sulfoxide at ambient temperature was investigated to give 2,4-diamino-5-(5-hydroxy-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-5H-chromeno[2,3-b]pyridine-3-carbonitrile with good yield. The structure of the previously unknown chromeno[2,3-b]pyridine derivative was confirmed by elemental analysis, mass, nuclear magnetic resonance, and infrared spectroscopy data. The ADME (absorption, distribution, metabolism, and excretion) properties were also assessed. [ABSTRACT FROM AUTHOR]

An environment-friendly photochemical approach to the synthesis of 4a,7a-dihydroxy-1-(2-hydroxyethyl)-5-methyl-2′,3′,4a,5′,6′,7a-hexahydrospiro[cyclopenta[b]pyridine-4,4′-pyran]-2,7(1H,3H)-dione from 2-(4-(3-hydroxy-6-methyl-4-oxo-4H-pyran-2-yl)tetrahydro-2H-pyran-4-yl)-N-(2-hydroxyethyl)acetamide was elaborated. The suggested method is based on the ESIPT-promoted contraction of 3-hydroxypyran-4-one fragment followed by intramolecular cyclization of generated in situ α-hydroxy-1,2-diketone intermediate. The distinctive feature of the presented protocol is the employment of water as a solvent for the considered photoreaction. The structure of the obtained photoproduct was confirmed by 1H, 13C-NMR, IR spectroscopy and high-resolution mass spectrometry. [ABSTRACT FROM AUTHOR]

Solvents can have a tremendous influence on the rate and selectivity of chemical reactions, but their effects are not always well accounted for. In the present work, density functional theory computations are used to investigate the influence of solvent on the Diels–Alder reactions of 9-methylanthracene with (5-oxo-2H-furan-2-yl) acetate and different anhydrides considering the overall reaction rates as well as selectivity between possible isomeric products. Crucially, we find that overall reaction rates are higher in non-polar toluene, whereas selectivity is enhanced in the polar solvent acetone. In the case of (5-oxo-2H-furan-2-yl) acetate, the difference in the reaction barriers is enhanced by 2.4 kJ/mol in acetone as compared to the gas phase, halving the yield of the side product. Similar results are found for the reaction of 9-methylanthracene with chloro-maleic anhydride and cyano-maleic anhydride, highlighting the generality of the trends observed. After presenting the energetics, a detailed discussion of the reactivity is given using electrostatic potentials, frontier orbitals, reactivity indices and Fukui functions. In summary, this study highlights the importance of solvent in influencing reaction rates and illustrates the possibility of studying its effects computationally. [ABSTRACT FROM AUTHOR]

The one-pot synthesis methodology has become the leading atom-economical approach for various chemical transformations in a single pot, without purifying intermediate compounds. Chromeno[2,3-b]pyridines are an important class of heterocyclic compounds with versatile biological profiles and other different applications The 5-aminopyrazole system represents a significant heterocyclic template that has gained considerable interest because of its long history of use in the pharmaceutical and agrochemical industries. In this communication, the one-pot transformation of salicylaldehyde, malononitrile dimer, and 2-cyanoacetohydrazide in an ethanol/pyridine mixture was investigated to provide 2,4-diamino-5-(5-amino-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-5H-chromeno[2,3-b]pyridine-3-carbonitrile in good yield. The structure of the novel compound was confirmed by means of elemental analysis, mass-, nuclear magnetic resonance, and infrared spectroscopy. [ABSTRACT FROM AUTHOR]

Dimethyl sulfoxide (DMSO) is widely used as a solvent in organic synthesis and in pharmacology because of its low cost, stability, and non-toxicity. Multicomponent reactions are a powerful synthetic tool for the rapid and efficient construction of complicated molecular frameworks. In this communication, the multicomponent transformation of salicylaldehyde, malononitrile dimer, and dimethyl malonate in DMSO at room temperature was carefully investigated to give dimethyl 2-(2,4-diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonate with good yield. The structure of the new compound was established by means of elemental analysis and mass, nuclear magnetic resonance, and infrared spectroscopy. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) is a crucial technique for analyzing mixtures consisting of small molecules, providing non-destructive, fast, reproducible, and unbiased benefits. However, it is challenging to perform mixture identification because of the offset of chemical shifts and peak overlaps that often exist in mixtures such as plant flavors. Here, we propose a deep-learning-based mixture identification method (DeepMID) that can be used to identify plant flavors (mixtures) in a formulated flavor (mixture consisting of several plant flavors) without the need to know the specific components in the plant flavors. A pseudo-Siamese convolutional neural network (pSCNN) and a spatial pyramid pooling (SPP) layer were used to solve the problems due to their high accuracy and robustness. The DeepMID model is trained, validated, and tested on an augmented data set containing 50,000 pairs of formulated and plant flavors. We demonstrate that DeepMID can achieve excellent prediction results in the augmented test set: ACC = 99.58%, TPR = 99.48%, FPR = 0.32%; and two experimentally obtained data sets: one shows ACC = 97.60%, TPR = 92.81%, FPR = 0.78% and the other shows ACC = 92.31%, TPR = 80.00%, FPR = 0.00%. In conclusion, DeepMID is a reliable method for identifying plant flavors in formulated flavors based on NMR spectroscopy, which can assist researchers in accelerating the design of flavor formulations. [ABSTRACT FROM AUTHOR]

New C3-substituted 5,6-dihydropyrrolo[2,1-a]isoquinolines have been synthesized via three-com-ponent domino reaction of 1-aroyl-3,4-dihydroisoquinolines, dimethyl acetylenedicarboxylate, and CH acids in anhydrous acetonitrile under microwave irradiation at 130°C. [ABSTRACT FROM AUTHOR]

In this mini-review, we present our concepts for designing multicomponent reactions with reference to a series of sequential radical reactions that we have developed. Radical reactions are well suited for the design of multicomponent reactions due to their high functional group tolerance and low solvent sensitivity. We have focused on the photolysis of interelement compounds with a heteroatom–heteroatom single bond, which readily generates heteroatom-centered radicals, and have studied the photoinduced radical addition of interelement compounds to unsaturated compounds. First, the background of multicomponent radical reactions is described, and basic concepts and methodology for the construction of multicomponent reactions are explained. Next, examples of multicomponent reactions involving two interelement compounds and one unsaturated compound are presented, as well as examples of multicomponent reactions involving one interelement compound and two unsaturated compounds. Furthermore, multicomponent reactions involving intramolecular cyclization processes are described. [ABSTRACT FROM AUTHOR]

The Warburg effect (or aerobic glycolysis), which was first described in 1926 by Otto Heinrich Warburg, consists of the change in glucose metabolism in cancer cells. In normal cells, glucose metabolism finalizes in the mitochondria through oxidative phosphorylation (OXPHOS) in the presence of oxygen. However, the Warburg effect describes a change in the glucose metabolism in cancer cells, consuming excess glucose and converting it into lactate independently of the presence of oxygen. During this process, a wide variety of enzymes can modify their expression and activity to contribute to the mechanism of deregulated cancer metabolism. Therefore, the modulation of enzymes regulating aerobic glycolysis is a strategy for cancer treatment. Although numerous enzymes play a role in regulating aerobic glycolysis, hexokinase 2 (HK2), pyruvate dehydrogenase kinase (PDK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) are worth mentioning. Numerous modulators of these enzymes have been described in recent years. This review aims to present and group, according to their chemical structure, the most recent emerging molecules targeting the above-mentioned enzymes involved in the Warburg effect in view of the future development of cancer treatments. [ABSTRACT FROM AUTHOR]

Here, we first report the 2′-acyloxy-1,3-dicarbonyl compound construction in a three-component oxidative reaction of alkyl ketene dimer with cyclic diacyl peroxide and trimethyl orthoformate. The discovered synthesis allows us to form 2′-functionalized 1,3-dicarbonyl compounds instead of the common 2-functionalized moiety. The reaction between 4-butylidene-3-propyloxetan-2-one and cyclopropyl malonoyl peroxide proceeds in the presence of trifluoroacetic acid and trimethyl orthoformate at 120 °C for 1 h. The synthesized compound was characterized by NMR spectroscopy, mass spectrometry, and IR spectroscopy. [ABSTRACT FROM AUTHOR]

1,2,5-Chalcogenadiazoles fused with electron-withdrawing heterocycles have been actively investigated for the preparation of organic photovoltaic materials. [1,2,5]Oxadiazolo[3,4-d]pyridazines are much less studied than other chalcogenadiazolopyridazines due to their low availability. In this communication, we report our study showing that 5,6-dihydro-[1,2,5]oxadiazolo[3,4-d]pyridazine-4,7-dione, a key precursor for the synthesis of 4,7-dihalo-[1,2,5]oxadiazolo[3,4-d]pyridazines, is formed via the cyclization of 1,2,5-oxadiazole-3,4-dicarbohydrazide in hydrochloric acid. The structure of the newly synthesized compound was established by means of elemental analysis; high-resolution mass spectrometry; 1H and 13C NMR; IR spectroscopy, and mass spectrometry. [ABSTRACT FROM AUTHOR]

Multicomponent reactions have been demonstrated as a promising tool for the creation of diverse molecular structures with enhanced efficiency, reduced waste, and a high atom economy. Arylglyoxal monohydrates with two different carbonyl groups are well known as worthwhile synthons in organic synthesis. 2-Pyrone and pyrimidine-2,4,6-trione are versatile building blocks for the synthesis of key intermediates in synthetic organic chemistry as well as in medicinal chemistry. A simple and efficient tandem Knoevenagel–Michael protocol for the synthesis of the previously unknown 5-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-phenylethyl)-1,3-dimet-hylpyrimidine-2,4,6(1H,3H,5H)-trione was elaborated. The suggested method is based on the multicomponent reaction of phenylglyoxal hydrate, 1,3-dimethylbarbituric acid, and 4-hydroxy-6-methyl-2H-pyran-2-one. The structure of the synthesized compound was proven by 1H, 13C-NMR, and IR spectroscopy, mass spectrometry, and elemental analysis. A procedure for predicting the possible types of its biological activity was carried out for the title compound. [ABSTRACT FROM AUTHOR]

The biogenic polyamines, spermidine (Spd) and spermine (Spm), are present at millimolar concentrations in all eukaryotic cells, where they participate in the regulation of vitally important cellular functions. Polyamine analogs and derivatives are a traditional and important instrument for the investigation of the cellular functions of polyamines, enzymes of their metabolism, and the regulation of the biosynthesis of antizyme—a key downregulator of polyamine homeostasis. Here, we describe convenient gram-scale syntheses of a set of C-methylated analogs of Spd. The biochemical properties of these compounds and the possibility for the regulation of their activity by moving a methyl group along the polyamine backbone and by changing the stereochemistry of the chiral center(s) are discussed. [ABSTRACT FROM AUTHOR]

Some of the most important transformations in organic chemistry are rearrangement reactions, which play a crucial role in increasing synthetic efficiency and molecular complexity. The development of synthetic strategies involving rearrangement reactions, which can accomplish synthetic goals in a very efficient manner, has been an evergreen topic in the synthetic chemistry community. Xanthenes, pyridin-2(1H)-ones, and 1,6-naphthyridines have a wide range of biological activities. In this work, we propose the thermal rearrangement of 7,9-dihalogen-substituted 5-(2-hydroxy-6-oxocyclohexyl)-5H-chromeno[2,3-b]pyridines in DMSO. Previously unknown 5,7-dihalogenated 5-(2,3,4,9-tetrahydro-1H-xanthen-9-yl)-6-oxo-1,6-dihydropyridines and 10-(3,5-dihalogen-2-hydroxyphenyl)-5,6,7,8,9,10-hexahydrobenzo[b][1,6]naphthyridines were synthesized with excellent yields (90–99%). The investigation of the transformation using 1H-NMR monitoring made it possible to confirm the ANRORC mechanism. The structures of synthesized compounds were confirmed by 2D-NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be one of the main causes of hospital-acquired infections in all regions of the world, while linezolid is one of the only commercially available oral antibiotics available against this dangerous gram-positive pathogen. In this study, the antibacterial activity from 32 analogues of synthetic gamma-lactam heterocycles against MRSA was determined. Amongst screened analogues for the minimum inhibitory concentration (MIC) assay, compound MFM514 displayed good inhibitory activity with MIC values of 7.8–15.6 µg/mL against 30 MRSA and 12 methicillin-sensitive S. aureus (MSSA) clinical isolates, while cytotoxicity evaluations displayed a mean inhibitory concentration (IC50) value of > 625 µg/mL, displaying a potential to becoming as a lead compound. In subsequent animal studies for MFM514, a single-dose oral acute toxicity test revealed an estimated mean lethal dose (LD50) value of <5000 mg/kg, while in the mice infection test, a mean effective dose (ED50) value of 29.39 mg/kg was obtained via oral administration. These results suggest that gamma-lactam carbon skeleton, particularly MFM514, is highly recommended to be evaluated further as a new safe and efficacious orally delivered antibacterial agent against MRSA. [ABSTRACT FROM AUTHOR]

An efficient one-pot three-component reaction for the synthesis of 5-[naphthalen-1(2)yl]-5H-chromeno[2,3-b]pyridine derivatives has been developed. The synthesis was achieved by reacting salicyl-aldehydes, 2-aminopropene-1,1,3-tricarbonitrile, and naphthols catalyzed by triethylamine under solvent-free conditions at 120°C. The reaction involves formation of two C–C bonds, one C–O bond, and one C–N bond in a single synthetic operation. The final products can be isolated by simple filtration after treatment of the reaction mixture with ethanol. This rapid one-pot reaction does not require chromatographic purification and provides the products in good yields. [ABSTRACT FROM AUTHOR]

In recent years, the application of privileged structures has become a powerful approach in the discovery of new biologically active molecules. Ion pairing is a strategy used to enhance the permeation of ionized topical drugs. A convenient and efficient method for the synthesis of triethylammonium 2-(3-hydroxy-2-oxoindolin-3-yl)-5,5-dimethyl-3-oxocyclohex-1-en-1-olate has been developed. The presented protocol includes an aldol reaction and the formation of an ammonium salt. Triethylamine is both a reactant and a catalyst in the process. The structure of the synthesized title compound has been established by 1H, 13C-NMR and IR spectroscopy, mass spectrometry, and elemental analysis. [ABSTRACT FROM AUTHOR]

Piperidines are among the most important synthetic fragments for designing drugs and play a significant role in the pharmaceutical industry. Their derivatives are present in more than twenty classes of pharmaceuticals, as well as alkaloids. The current review summarizes recent scientific literature on intra- and intermolecular reactions leading to the formation of various piperidine derivatives: substituted piperidines, spiropiperidines, condensed piperidines, and piperidinones. Moreover, the pharmaceutical applications of synthetic and natural piperidines were covered, as well as the latest scientific advances in the discovery and biological evaluation of potential drugs containing piperidine moiety. This review is designed to help both novice researchers taking their first steps in this field and experienced scientists looking for suitable substrates for the synthesis of biologically active piperidines. [ABSTRACT FROM AUTHOR]

Quinolizidine and azaphenalene alkaloids are common in nature and exhibit a pharmaceutical activity, which stirs up increased interest in expanding the range of methods for the synthesis of the corresponding derivatives. In this work, we attempted to adapt our previously presented method for the synthesis of tetrahydropyridines to the preparation of potential precursors for these heterocycles as a separate development of a necessary intermediate stage. To this end, we studied the reactions of β-styrylmalonates with N-protected cross-conjugated azatrienes in the presence of Sn(OTf)2. Moreover, the regioselectivity of the process involving unsymmetrically substituted azatrienes was estimated. The diene character of vinyltetrahydropyridines was studied in detail with the participation of PTAD. Finally, for the Ts-protected highly functionalized vinyltetrahydropyridines synthesized, a detosylation method to give new desired azadiene structures as precursors of the quinolizidine core was suggested. [ABSTRACT FROM AUTHOR]

Chromeno[2,3-b]pyridines are substances demanded in medicinal and material chemistry. PASE (pot, atom, and step economy) and in particular one-pot approaches are key green chemistry techniques that are applied for the synthesis of heterocyclic compounds. In this case, the PASE approach was extended with 'component economy', as solvent was used also as reactant (solvent-involved reaction). This approach was adopted for the one-pot synthesis of previously unknown O-substituted 5-alkoxy-5H-chromeno[2,3-b]pyridines via two-step transformation, namely the reaction of salicylaldehydes and malononitrile dimer, with the subsequent addition of alcohol. The mechanistic studies revealed the possibility of concurrent reaction. The studies aided in optimizing the reaction conditions for the best yields (77–93%). Thus, the one-pot reaction proceeds efficient and quickly, and the work-up procedure (only simple filtering) is very convenient. The structure of synthesized chromeno[2,3-b]pyridines was confirmed by 2D NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Over the past decades, studies of cyclic diacyl peroxides have shown superior or even fundamentally new reactivity compared to their acyclic counterparts in various reactions. Previously, the scope of cyclic diacyl peroxides was limited to the mono peroxy compounds. The first doubled cyclic diacyl peroxide is presented herein. The diperoxide was characterized by NMR spectroscopy, mass spectrometry, and IR spectroscopy. The structure of 4,4′-(butane-1,4-diyl)bis(4-methyl-1,2-dioxolane-3,5-dione) was confirmed by X-ray diffraction analysis. The novel diperoxide was prepared in a 55% overall yield in three steps from dibromobutane and diethyl methylmalonate. [ABSTRACT FROM AUTHOR]

Chiral primary α-amino amides, consisting of an adjacent enamine bonding site (Bronsted base site), a hydrogen bonding site (Bronsted acid site), and flexible bulky substituent groups to modify the steric factor, are proving to be extremely valuable bifunctional organocatalysts for a wide range of asymmetric organic transformations. Primary α-amino amides are less expensive alternatives to other primary amino organocatalysts, such as chiral diamines and cinchona-alkaloid-derived primary amines, as they are easy to synthesize, air-stable, and allow for the incorporation of a variety of functional groups. In recent years, we have demonstrated the catalytic use of simple primary α-amino amides and their derivatives as organocatalysts for the aldol reaction, Strecker reaction, Michael tandem reaction, allylation of aldehydes, reduction of N-Aryl mines, opening of epoxides, hydrosilylation, asymmetric hydrogen transfer, and N-specific nitrosobenzene reaction with aldehydes. [ABSTRACT FROM AUTHOR]

Carrying out organic reactions in water has attracted much attention. Catalytic reactions in water with metallosurfactants, which have both a metallocenter and the surface activity necessary for solubilizing hydrophobic reagents, are of great demand. Herein we proposed new approach to the synthesis of NHC PEPPSI metallosurfactants based on the sequential functionalization of imidazole 4,5-dicarboxylic acid with hydrophilic oligoethylene glycol and lipophilic alkyl fragments. Complexes of different lipophilicity were obtained, and their catalytic activity was studied in model reduction and Suzuki–Miyaura reactions. A comparison was made with the commercial PEPPSI-type catalytic systems designed by Organ. It was found that the reduction reaction in an aqueous solution of the metallosurfactant with the tetradecyl lipophilic fragment was three times more active than the commercially available PEPPSI complexes, which was associated with the formation of stable monodisperse aggregates detected by DLS and TEM. [ABSTRACT FROM AUTHOR]

In the wake of increasing demands on skin health, we propose simple, natural, and safe dry facial masks that restrict melanin synthesis. Phyllanthus emblica (P. emblica) is made into powders via a low-temperature extraction and freeze-drying process to serve as a natural agent. Next, it is added to mixtures containing Polyvinylpyrrolidone (PVP) and Chitosan (CS), after which the blends are electrospun into PVP/CS/P. emblica nanofiber membrane dry facial masks using the electrospinning technique. The dry facial masks are evaluated using the calibration analysis method, extraction rate test, scanning electron microscopy (SEM), release rate test, tyrosinase inhibition assay, biocompatibility test, and anti-inflammatory capacity test. Test results indicate that when the electrospinning mixture contains 29.0% P. emblica, the nanofibers have a diameter of ≤214.27 ± 74.51 nm and a water contact angle of 77.25 ± 2.21. P. emblica is completely released in twenty minutes, and the tyrosinase inhibition rate reaches 99.53 ± 0.45% and the cell activity ≥82.60 ± 1.30%. Moreover, the anti-inflammatory capacity test results suggest that dry facial masks confine inflammatory factors. PVP/CS/P. emblica nanofiber dry facial masks demonstrate excellent tyrosinase inhibition and are hydrophilic, biocompatible, and inflammation-free. The dry facial masks are a suitable material that is worthwhile exploring and applying to the cosmetic field. [ABSTRACT FROM AUTHOR]

A series of symmetrical dibenzylidene derivatives of cyclobutanone were synthesized with the goal of studying the physicochemical properties of cross-conjugated dienones (ketocyanine dyes). The structures of the products were established and studied by X-ray diffraction and by NMR and electronic spectroscopy. All the products had E,E-geometry. The oxidation and reduction potentials of the dienones were determined by cyclic voltammetry. The potentials were shown to depend on the nature, position, and number of substituents in the benzene rings. A linear correlation was found between the difference of the electrochemical oxidation and reduction potentials and the energy of the long-wavelength absorption maximum. This correlation can be employed to analyze the properties of other compounds of this type. Quantum chemistry was used to explain the observed regularities in the electrochemistry, absorption, and fluorescence of the dyes. The results are in good agreement with the experimental redox potentials and spectroscopy data. [ABSTRACT FROM AUTHOR]

The review describes syntheses of new benzo-fused spiro heterocycles by reactions of isatins, oxindoles, and indenoquinoxalines with nitroalkenes, chalcones in the presence of proline or thioproline, amino acids, malononitrile, cyclic and acyclic aliphatic 1,3-diketones or aldehydes, and ethyl acetoacetate. Some compounds exhibiting various biological activities have been noted. [ABSTRACT FROM AUTHOR]

Due to the introduction of oxygen atoms, N-oxide energetic compounds have a unique oxygen balance, excellent detonation properties, and a high energy density, attracting the extensive attention of researchers all over the world. N-oxides are classified into two categories based on the structural characteristics of their skeletons: azine N-oxides and azole N-oxides, whose N→O coordination bonds are formed during cyclization. There are six kinds of azine N-oxides, namely 1,2,3,4-tetrazine-1,3-dioxide, 1,2,3,5-tetrazine-2-oxide, 1,2,3-triazine-3-oxide, 1,2,3-triazine-2-oxide, pyridazine-1,2-dioxide, and pyrazine-1-oxide. Azole N-oxides include 1,2,5-oxadiazole-2-oxide, pyrazole-1-oxide, and triazole-1-oxide. Synthetic strategies towards these two categories of N-oxides are fully reviewed. Corresponding reaction mechanisms towards the aromatic N-oxide frameworks and examples that use the frameworks to create high-energy substances are discussed. Moreover, the energetic properties of N-oxide energetic compounds are compared and summarized. [ABSTRACT FROM AUTHOR]

Background: A number of research were conducted on the pyran and thiophene derivatives, which were attributed to have a wide range of biological activities, including anti-plasmodial, as well as acting as caspase, hepatitis C and cancer inhibitors., Objective: The multicomponent reactions of the 5-acetyl-2-amino-4-(phenylamino)-thiophene-3-carbonitrile produced biologically active target molecules like pyran and their fused derivatives. Comparison between regular catalytic multi-component reactions and solvent-free ionic liquids immobilized multicomponent was studied., Methods: The multicomponent reactions in this work were carried out not only under the reflux conditions using triethylamine as a catalyst but also in solvent-free ionic liquids immobilized magnetic nanoparticles (MNPs) catalysts., Results: Through this work, thirty-one new compounds were synthesized and characterized and were evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The most active compounds were further screened toward seventeen cancer cell lines classified according to the disease. In addition, the effect of compound 11e on the A549 cell line was selected to make further morphological changes in the cell line. The Molecular docking studies of 11e and 11f were carried and promising results were obtained., Conclusion: The synthesis of heterocyclic compounds derived from thiophene derivatives has been receiving significant attention. After a detailed optimizing study, it has been found that the solvent-free ionic liquids immobilized multi-component syntheses afforded a high yield of compounds, opening a greener procedure for this synthetically relevant transformation. Many of the synthesized compounds can be considered anticancer agents, enhancing further studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ionic liquids (ILs) are poorly-coordinated ionic salts that can exist as a liquid at room temperatures (or <100 °C). ILs are also referred to as "designer solvents" because so many of them have been created to solve particular synthetic issues. ILs are regarded as "green solvents" because they have several distinctive qualities, including better ionic conduction, recyclability, improved solvation ability, low volatility, and thermal stability. These have been at the forefront of the most innovative fields of science and technology during the past few years. ILs may be employed in new drug formulation development and drug design in the field of pharmacy for various functions such as improvement of solubility, targeted drug delivery, stabilizer, permeability enhancer, or improvement of bioavailability in the development of pharmaceutical or vaccine dosage formulations. Ionic liquids have become a key component in various areas such as synthetic and catalytic chemistry, extraction, analytics, biotechnology, etc., due to their superior abilities along with highly modifiable potential. This study concentrates on the usage of ILs in various pharmaceutical applications enlisting their numerous purposes from the delivery of drugs to pharmaceutical synthesis. To better comprehend cuttingedge technologies in IL-based drug delivery systems, highly focused mechanistic studies regarding the synthesis/preparation of ILs and their biocompatibility along with the ecotoxicological and biological effects need to be studied. The use of IL techniques can address key issues regarding pharmaceutical preparations such as lower solubility and bioavailability which plays a key role in the lack of effectiveness of significant commercially available drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Elaboration of a convenient route towards donor-substituted pyrazoles from heteropropargyl precursors is challenging due to a number of thermodynamically favorable side reactions (e.g., acetylene–allene isomerization and Glaser homocoupling). In this work, Sonogashira cross-coupling conditions of 4-tert-butylphenyl propargyl ether with benzoyl chloride followed by tandem Michael addition/cyclocondensation with hydrazine into 3,5-disubstituted pyrazole (kinetic control), as well as cycloisomerization conditions of ketoacetylene intermediate into 2,5-disubstituted furan (thermodynamic control), were established through a variation of the catalyst loading, solvent polarity, excess of triethylamine, and time of reaction. During the optimization of process parameters, a number of by-products represented by a monophosphine binuclear complex (PPh3PdI2)2 with two bridging iodine atoms and diyne were identified and isolated in the pure form. The quantum-chemical calculations and solution-state 1H/13C NMR spectroscopy suggested that the 5(3)-(4-tert-butylphenyloxy)methoxy-3(5)-phenyl-1H-pyrazole exists in the tautomeric equilibrium in a polar methanol solvent and that individual tautomers could be characterized in case aprotic solvents employed. The pyrazole features a unique tetramer motif in the crystal phase formed by alternating 3(5)-phenyl-1H-pyrazole tautomers, which was stabilized by N–H···N bonds and stacking interactions of pyrazole rings, whereas pyrazole dimers were identified in the gas phase. [ABSTRACT FROM AUTHOR]

The multicomponent reaction of aldehydes, cyano-containing C-H acids, esters of 3-oxocarboxylic acid and ammonium acetate led to unexpected results. The boiling of starting materials in methanol for one to two hours resulted in the formation of polysubstituted 1,4,5,6-tetrahydropyridines with two or three stereogenic centers. During the 2020 lockdown, we obtained key intermediates of this six-step domino reaction. A number of fast and slow reactions occurred during the prolonged stirring of the reaction mass at rt. Sequence: 1. Knoevenagel condensation; 2. Michael addition; 3. Mannich reaction; 4. cyclization—fast reactions and cyclization of the product polysubstituted 2-hydroxypiperidine—was isolated after 40 min stirring at rt. Further monitoring proved the slow dehydration of 2-hydroxypiperidine to obtain 3,4,5,6-tetrahydropyridine after 7 days. Then, four-month isomerization occurred with 1,4,5,6-tetrahydropyridine formation. All reactions were stereoselective. Key intermediates and products structures were verified by X-ray diffraction analysis. Additionally, we specified conditions for the selective intermediates' preparation. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) spectroscopy is highly unbiased and reproducible, which provides us a powerful tool to analyze mixtures consisting of small molecules. However, the compound identification in NMR spectra of mixtures is highly challenging because of chemical shift variations of the same compound in different mixtures and peak overlapping among molecules. Here, we present a pseudo-Siamese convolutional neural network method (pSCNN) to identify compounds in mixtures for NMR spectroscopy. A data augmentation method was implemented for the superposition of several NMR spectra sampled from a spectral database with random noises. The augmented dataset was split and used to train, validate and test the pSCNN model. Two experimental NMR datasets (flavor mixtures and additional flavor mixture) were acquired to benchmark its performance in real applications. The results show that the proposed method can achieve good performances in the augmented test set (ACC = 99.80%, TPR = 99.70% and FPR = 0.10%), the flavor mixtures dataset (ACC = 97.62%, TPR = 96.44% and FPR = 2.29%) and the additional flavor mixture dataset (ACC = 91.67%, TPR = 100.00% and FPR = 10.53%). We have demonstrated that the translational invariance of convolutional neural networks can solve the chemical shift variation problem in NMR spectra. In summary, pSCNN is an off-the-shelf method to identify compounds in mixtures for NMR spectroscopy because of its accuracy in compound identification and robustness to chemical shift variation. [ABSTRACT FROM AUTHOR]

Dimethyl sulfoxide (DMSO) is a cheap polar aprotic solvent used in organic synthesis and in pharmacology because of its low cost, high stability, and non-toxicity. Multicomponent reactions (MCRs) are highly convergent processes and have good atom, step, and pot economies. In this communication, the multicomponent transformation of salicylaldehyde, malononitrile dimer, and nitromethane in DMSO at room temperature was investigated to give 2,4-diamino-5-(nitromethyl)-5H-chromeno[2,3-b]pyridine-3-carbonitrile in good yield. The structure of the earlier unknown compound was confirmed by means of elemental analysis, mass-, nuclear magnetic resonance, and infrared spectroscopy. [ABSTRACT FROM AUTHOR]

Imidazopyridines constitute one of the most important scaffolds in medicinal chemistry, as their skeleton could be found in a myriad of biologically active molecules. Although numerous strategies were elaborated for imidazopyridine preparation in the 2010s, novel eco-compatible synthetic approaches have emerged, conscious of climate change concerns. In this framework, photochemical methods have been promoted to conceive this heterocyclic motif over the last decade. This review covers the recently published works on synthesizing highly functionalized imidazopyridines by light induction. [ABSTRACT FROM AUTHOR]

In this study, several different depolymerases encoded in the prophage regions of Acinetobacter baumannii genomes have been bioinformatically predicted and recombinantly produced. The identified depolymerases possessed multi-domain structures and were identical or closely homologous to various proteins encoded in other A. baumannii genomes. This means that prophage-derived depolymerases are widespread, and different bacterial genomes can be the source of proteins with polysaccharide-degrading activities. For two depolymerases, the specificity to capsular polysaccharides (CPSs) of A. baumannii belonging to K1 and K92 capsular types (K types) was determined. The data obtained showed that the prophage-derived depolymerases were glycosidases that cleaved the A. baumannii CPSs by the hydrolytic mechanism to yield monomers and oligomers of the K units. The recombinant proteins with established enzymatic activity significantly reduced the mortality of Galleria mellonella larvae infected with A. baumannii of K1 and K92 capsular types. Therefore, these enzymes can be considered as suitable candidates for the development of new antibacterials against corresponding A. baumannii K types. [ABSTRACT FROM AUTHOR]

We report efficient synthetic methodologies for the preparation of 3-amino and 3-hydroxy 3-pyrrolin-2-ones (unsaturated γ-lactams) through a multicomponent reaction of amines, aldehydes and acetylene or pyruvate derivatives. The densely substituted γ-lactam substrates show in vitro cytotoxicity, inhibiting the growth of the carcinoma human tumor cell lines RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma) and A549 (carcinomic human alveolar basal epithelial cell). In view of the possibilities for the diversity of the substituents that offer a multicomponent, synthetic methodology, an extensive structure–activity profile is presented. In addition, the bioisosteric replacement of the flat ester group by a tetrahedral phosphonate or phosphine oxide moiety in γ-lactam substrates leads to increased growth inhibition activity. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism. [ABSTRACT FROM AUTHOR]

This study addressed the preparation and characterization of polyethylene glycol-substituted 1-methyl-imidazolium hydroxide supported on magnetic nanoparticles (MNP@PEG-ImOH) by FESEM, FT-IR, EDAX, TEM, TGA, VSM, and XRD techniques. The catalytic activity of MNP@PEG-ImOH has been examined in Knoevenagel condensation between active methylene compounds and aromatic aldehydes in aqueous medium at room temperature. Numerous benefits of the catalytic system, such as higher yields of the products, shorter reaction time, reusability and recyclability of the catalyst, simplified work-up, and more acceptable reaction conditions, have been demonstrated. It is possible to easily isolate the catalyst from the reaction mixture by an external magnet and reapply it in the consequent reactions with no remarkable loss of activity. [ABSTRACT FROM AUTHOR]

A facile synthesis of para-quinones derived from fused benzimidazoles with a bridgehead nitrogen atom was developed. The heterocyclic quinone core formed as a result of reductive cyclization of ortho-nitroarenes containing alicyclic and aromatic azaheterocycles. Functionalization of 1,2,3,4-tetrahydro- and pyrido[1,2-a]benzimidazoles via SEAr, condensation, and reduction reactions allowed synthesis of amino derivatives which were oxidized with KNO3 in H2SO4 to obtain novel heterocyclic quinones. [ABSTRACT FROM AUTHOR]

Electrospray ionization (ESI) high resolution mass spectra of positively charged ions (the first and the second order) of protonated molecules of isomeric β-(1→6)-linked cyclic tetrasaccharides of the Glcp2GlcpN2 composition were recorded and interpret. It was shown that the second-order mass spectra of these compounds have some differences reflecting the mutual positions of the glucopyranose and glucosamine residues. The most significant qualitative differences were observed for MS/MS spectra of doubly protonated, doubly charged molecules. [ABSTRACT FROM AUTHOR]

Dimethyl sulfoxide is a widely used solvent in organic synthesis and in the pharmaceutical industry because of its low cost, stability, and low toxicity. Multicomponent reactions are an advanced approach that has become an efficient, economical, and eco-friendly substitute for the conventional sequential multi-step synthesis of various biologically active compounds. This approach was adopted for the synthesis of previously unknown 2-(2,4-diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonic acids via transformation of salicylaldehydes, malononitrile dimer, and malonic acid. It was shown that the use of DMSO at room temperature makes it possible to synthesize previously unavailable compounds. The investigation of the reaction mechanism using 1H-NMR monitoring made it possible to confirm the proposed mechanism of the transformation. The structure of synthesized 5H-chromeno[2,3-b]pyridines was confirmed by 2D-NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a key signaling molecule that acts in various physiological processes such as cellular metabolism, vasodilation and transmission of nerve impulses. A wide number of vascular diseases as well as various immune and neurodegenerative disorders were found to be directly associated with a disruption of NO production in living organisms. These issues justify a constant search of novel NO-donors with improved pharmacokinetic profiles and prolonged action. In a series of known structural classes capable of NO release, heterocyclic NO-donors are of special importance due to their increased hydrolytic stability and low toxicity. It is no wonder that synthetic and biochemical investigations of heterocyclic NO-donors have emerged significantly in recent years. In this review, we summarized recent advances in the synthesis, reactivity and biomedical applications of promising heterocyclic NO-donors (furoxans, sydnone imines, pyridazine dioxides, azasydnones). The synthetic potential of each heterocyclic system along with biochemical mechanisms of action are emphasized. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) have been extensively explored and implemented in different areas, ranging from sensors and actuators to the biomedical field. The increasing attention devoted to ILs centers on their unique properties and possible combination of different cations and anions, allowing the development of materials with specific functionalities and requirements for applications. Particularly for biomedical applications, ILs have been used for biomaterials preparation, improving dissolution and processability, and have been combined with natural and synthetic polymer matrixes to develop IL-polymer hybrid materials to be employed in different fields of the biomedical area. This review focus on recent advances concerning the role of ILs in the development of biomaterials and their combination with natural and synthetic polymers for different biomedical areas, including drug delivery, cancer therapy, tissue engineering, antimicrobial and antifungal agents, and biosensing. [ABSTRACT FROM AUTHOR]

An efficient synthetic methodology for the preparation of 3-amino 1,5-dihydro-2H-pyrrol-2-ones through a multicomponent reaction of amines, aldehydes, and pyruvate derivatives is reported. In addition, the densely substituted lactam substrates show in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell lines HEK293 (human embryonic kidney), MCF7 (human breast adenocarcinoma), HTB81 (human prostate carcinoma), HeLa (human epithelioid cervix carcinoma), RKO (human colon epithelial carcinoma), SKOV3 (human ovarian carcinoma), and A549 (carcinomic human alveolar basal epithelial cell). Given the possibilities in the diversity of the substituents that offer the multicomponent synthetic methodology, an extensive structure-activity profile is presented. In addition, both enantiomers of phosphonate-derived γ-lactam have been synthesized and isolated and a study of the cytotoxic activity of the racemic substrate vs. its two enantiomers is also presented. Cell morphology analysis and flow cytometry assays indicate that the main pathway by which our compounds induce cytotoxicity is based on the activation of the intracellular apoptotic mechanism. [ABSTRACT FROM AUTHOR]

The ammonium salts of many drugs have significantly improved the solubility and, accordingly, the bioavailability of medicinal substances in the human body. 5-(4-Hydroxy-2-oxo-2H-chromen-3-yl)-5H-chromeno[2,3-b]pyridines are potential NPY1R ligands, which are attractive for antiobesity treatment. Ammonium salts of 5H-chromeno[2,3-b]pyridines were previously unknown. In this communication, it was found that the four-component reaction of salicylaldehyde, 2-aminoprop-1-ene-1,1,3-tricarbonitrile, 4-Hydroxy-2H-chromen-2-one and amines results in the formation of ammonium salts of 5-(3-chromenyl)-5H-chromeno[2,3-b]pyridines. The structure of these previously unknown compounds was confirmed by means of 1H, 13C NMR and IR spectroscopy, mass spectrometry and elemental analysis. [ABSTRACT FROM AUTHOR]

The binding and stabilizing effect of arginine residues in certain aldolases served as inspiring source for the development of a family of amino acylguanidine organocatalysts. Screening and optimization led to identify the threonine derivative as the most suitable catalyst for the asymmetric aldol addition of hydroxyacetone, affording the syn diastereomer in high ee. In contrast, the proline derivative yielded the anti diasteromer. MMFF models suggest the presence of an extensive hydrogen bonding network between the acylguanidinium group and the reaction intermediates. [ABSTRACT FROM AUTHOR]

A new family of sterically hindered alkyl(tri-tert-butyl) phosphonium salts (n-CnH2n+1 with n = 2, 4, 6, 8, 10, 12, 14, 16, 18, 20) was synthesized and evaluated as stabilizers for the formation of palladium nanoparticles (PdNPs), and the prepared PdNPs, stabilized by a series of phosphonium salts, were applied as catalysts of the Suzuki cross-coupling reaction. All investigated phosphonium salts were found to be excellent stabilizers of metal nanoparticles of small catalytically active size with a narrow size distribution. In addition, palladium nanoparticles exhibited exceptional stability: the presence of phosphonium salts prevented agglomeration and precipitation during the catalytic reaction. [ABSTRACT FROM AUTHOR]

High-resolution electrospray mass spectra (MS and MS/MS CID) of positive ions of a series of protonated, ammoniated, and metallated molecules of cyclic N-substituted oligo-β-(1→6)-D-glucosamines differing in cycle size and N-acyl substituents were registered and interpreted. It was shown that the main type of fragmentation is a cleavage of glycosidic bonds of a cycle, and in some cases fragmentation of amide side chains is possible. If labile fragments in substituents (e.g., carbohydrate chains) are present, a decay of the cycle and an elimination of labile fragments are of comparable possibility. It was found that in some cases rearrangements with loss of an internal carbohydrate residue (IRL), or an internal part of a side chain, are feasible. [ABSTRACT FROM AUTHOR]

The Pot, Atom, and Step Economy (PASE) approach is based on the Pot economy principle and unites it with the Atom and Step Economy strategies; it ensures high efficiency, simplicity and low waste formation. The PASE approach is widely used in multicomponent chemistry. This approach was adopted for the synthesis of previously unknown hydroxyquinolinone substituted chromeno[2,3-b]pyridines via reaction of salicylaldehydes, malononitrile dimer and hydroxyquinolinone. It was shown that an ethanol-pyridine combination is more beneficial than other inorganic or organic catalysts. Quantum chemical studies showed that chromeno[2,3-b]pyridines has potential for corrosion inhibition. Real time 1H NMR monitoring was used for the investigation of reaction mechanism and 2-((2H-chromen-3-yl)methylene)malononitrile was defined as a key intermediate in the reaction. [ABSTRACT FROM AUTHOR]