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In the present study, we characterize the biological activity of a newly designed and synthesized series of 15 compounds 2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl] derivatives of pyrrolo[3,4-c]pyrrole 3a–3o. The compounds were obtained with good yields of pyrrolo[3,4-c]pyrrole scaffold 2a–2c with secondary amines in C2H5OH. The chemical structures of the compounds were characterized by 1H-NMR, 13C-NMR, FT-IR, and MS. All the new compounds were investigated for their potencies to inhibit the activity of three enzymes, i.e., COX-1, COX-2, and LOX, by a colorimetric inhibitor screening assay. In order to analyze the structural basis of interactions between the ligands and cyclooxygenase/lipooxygenase, experimental data were supported by the results of molecular docking simulations. The data indicate that all of the tested compounds influence the activity of COX-1, COX-2, and LOX. [ABSTRACT FROM AUTHOR]

A new series of tetrasubstituted pyrrole derivatives (TSPs) was synthesized based on a previously developed hypothesis on their ability to mimic hydrophobic protein motifs. The resulting new TSPs were endowed with a significant toxicity against human epithelial melanoma A375 cells, showing IC50 values ranging from 10 to 27 μM, consistent with the IC50 value of the reference compound nutlin-3a (IC50 = 15 μM). In particular, compound 10a (IC50 = 10 μM) resulted as both the most soluble and active among the previous and present TSPs. The biological investigation evidenced that the anticancer activity is related to the activation of apoptotic cell-death pathways, supporting our rational design based on the ability of TSPs to interfere with PPI involved in the cell cycle regulation of cancer cells and, in particular, the p53 pathway. A reinvestigation of the TSP pharmacophore by using DFT calculations showed that the three aromatic substituents on the pyrrole core are able to mimic the hydrophobic side chains of the hot-spot residues of parallel and antiparallel coiled coil structures suggesting a possible molecular mechanism of action. A structure–activity relationship (SAR) analysis which includes solubility studies allows us to rationalize the role of the different substituents on the pyrrole core. [ABSTRACT FROM AUTHOR]

As the key intermediates in metal‐promoted/catalyzed C−C bond coupling reactions of nitriles and alkynes, azametallacyclopentadienes, M(N=CR1−CR2=CR3), are an important class of azametallacycles. Although the first authentic azametallacyclopentadienes were documented in 1986, their chemistry towards solid‐state structures, intrinsic reactivity, and synthetic application was rarely investigated for a long time. At the beginning of this century, seminal works about the applications of azametallacyclopentadienes in the synthesis of heterocycles, including multi‐substituted pyridines, isoquinolines, furans, and pyrroles were reported. Subsequently, a series of new complexes with this motif, namely the Group 4, aluminum, actinide, and rare‐earth azametallacyclopentadienes were isolated and structurally characterized. Among them, the rare‐earth azametallacyclopentadiene expresses high reactivity towards unsaturated molecules, such as nitriles, isocyanides, and Mo(CO)6 to provide novel fused metallacycles. In this Concept, we reviewed the advances in the preparation, reactivity, and synthetic application of azametallacyclopentadienes in the past twenty years. [ABSTRACT FROM AUTHOR]

In this study, the Ni(II) Schiff base/SBA-15 catalyst was successfully synthesized and characterized by employing FT-IR, XRD, TGA, EDX, ICP-OES, TEM, and SEM analysis. In addition, BJH and BET techniques were used to determine the specific surface area, pore size, and pore volume of the catalyst, which were 538 m2 g−1, 6 nm, and 1.01 cm3 g−1, correspondingly. Under favorable conditions, we have designed a one-pot multicomponent reaction combining aromatic amines, aldehydes, nitroalkanes, and 1,3-dicarbonyl compounds in conjunction with the presence of the Ni(II) Schiff base/SBA-15 as a heterogeneous catalyst to synthesize a range of functionalized pyrroles in reasonable to excellent yields an admirable yield percentage (94%), a short reaction time of approximately 8 h, mild reaction conditions of 70 °C, a wide range of substrates, the possibility of large-scale synthesis, low cost, and the avoidance of hazardous reagents and solvents. In addition, this method can synthesize more desirable pyrroles by adding or altering numerous functional groups to the reactants in a one-pot process. Specifically, a Hammett plot variant was employed to evaluate the reaction effectively. [ABSTRACT FROM AUTHOR]

In this paper, potentiostatic and galvanostatic deposition (electrochemical deposition) processes have been used for the obtained of a new composite polymer: N-methylpyrrole-sodium 1-dodecanesulfonate/poly 2-methylthiophene (PNMPY-1SSD/P2MT) coatings over brass electrode for corrosion protection. The sodium 1-dodecanesulfonate as a dopant ion employed in the electropolymerization procedure can have a meaningful effect on the anti-corrosion protection of the composite polymeric film by stopping the penetration of corrosive ions. The composite coatings have been characterized by cyclic voltammetry, Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) procedures. The anti-corrosion performance of PNMPY-1SSD/P2MT coated brass has been investigated by potentiostatic and potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) practices in 0.5 M H2SO4 medium. The corrosion assessment of PNMPY-1SSD/P2MT coated brass was noticed to be ~9 times diminished than of uncoated brass, and the efficiency of these protective coatings of this coating is above 90%. The highest effectiveness is realized by the electrochemical deposition of PNMPY-1SSD/P2MT obtained at 1.1 V and 1.4 V potential applied and at 0.5 mA/cm2 and 1 mA/cm2 current densities applied in molar ratio 5:3. The outcomes of the corrosion tests denoted that PNMPY-1SSD/P2MT coatings assure good anti-corrosion protection of brass in corrosive media. [ABSTRACT FROM AUTHOR]

Covalent functionalization of tungsten disulfide (WS2) with photo‐ and electro‐active nickel‐porphyrin (NiP) is reported. Exfoliated WS2 interfacing NiP moieties with 1,2‐dithiolane linkages is assayed in the oxygen evolution reaction under both dark and illuminated conditions. The hybrid material presented, WS2−NiP, is fully characterized with complementary spectroscopic, microscopic, and thermal techniques. Standard yet advanced electrochemical techniques, such as linear sweep voltammetry, electrochemical impedance spectroscopy, and calculation of the electrochemically active surface area, are used to delineate the catalytic profile of WS2−NiP. In‐depth study of thin films with transient photocurrent and photovoltage response assays uncovers photo‐enhanced electrocatalytic behavior. The observed photo‐enhanced electrocatalytic activity of WS2−NiP is attributed to the presence of Ni centers coordinated and stabilized by the N4 motifs of tetrapyrrole rings at the tethered porphyrin derivative chains, which work as photoreceptors. This pioneering work opens wide routes for water oxidation, further contributing to the development of non‐noble metal electrocatalysts. [ABSTRACT FROM AUTHOR]

The reaction of 3,3-diaminoacrylonitriles with DMAD and 1,2-dibenzoylacetylene was studied. It is shown that the direction of the reaction depends on the structure both of acetylene and of diaminoacrylonitrile. In the reaction of DMAD with acrylonitriles bearing a monosubstituted amidine group, 1-substituted 5-amino-2-oxo-pyrrole-3(2H)ylidenes are formed. On the other hand, a similar reaction of acrylonitriles containing the N,N-dialkylamidine group affords 1-NH-5-aminopyrroles. In both cases, pyrroles containing two exocyclic double bonds are formed in high yields. A radically different type of pyrroles containing one exocyclic C=C bond and sp3 hybrid carbon in the cycle is formed in reactions of 3,3-diaminoacrylonitriles with 1,2-diaroylacetylenes. As in reactions with DMAD, the interaction of 3,3-diaminoacrylonitriles with 1,2-dibenzoylacetylene can lead, depending on the structure of the amidine fragment, both to NH- and 1-substituted pyrroles. The formation of the obtained pyrrole derivatives is explained by the proposed mechanisms of the studied reactions. [ABSTRACT FROM AUTHOR]

Herein we report acid mediated two and three‐component domino reactions of cyclic enamines such as 2‐amino‐1,4‐naphthoquinone, and 6‐amino‐1,3‐dimethyluracil with arylglyoxals for the synthesis of diverse fused pyrroles. The two‐component reaction of arylglyoxal and 2‐amino‐1,4‐naphthoquinone in the acetic acid medium provided substituted naphthoquinone‐fused pyrroles tethered with hydroxyl and aryl substituents. On the other hand, under similar reaction conditions, the reaction of phenylglyoxal with 6‐amino‐1,3‐dimethyluracil provided an unusual bipyrrolopyrimidine with a quaternary carbon center following a domino reaction involving the formation of five new sigma bonds in one‐pot. Interestingly, the reaction of arylglyoxals with 6‐amino‐1,3‐dimethyluracil in ethanol medium in the presence of 10‐mol% PTSA provided a three‐component product having pyrimidine fused pyrrole linked with 6‐aminouracil moiety. We have also developed a three‐component reaction of 2‐amino‐1,4‐naphthoquinone, arylglyoxals, and 4‐hydroxy‐1‐methylquinolin‐2(1H)‐one for the synthesis of naphthoquinone‐fused pyrroles linked with hydroxyquinoline derivatives. [ABSTRACT FROM AUTHOR]

Actinomycetes are essential sources of numerous bioactive secondary metabolites with diverse chemical and bioactive properties. Lichen ecosystems have piqued the interest of the research community due to their distinct characteristics. Lichen is a symbiont of fungi and algae or cyanobacteria. This review focuses on the novel taxa and diverse bioactive secondary metabolites identified between 1995 and 2022 from cultivable actinomycetota associated with lichens. A total of 25 novel actinomycetota species were reported following studies of lichens. The chemical structures and biological activities of 114 compounds derived from the lichen-associated actinomycetota are also summarized. These secondary metabolites were classified into aromatic amides and amines, diketopiperazines, furanones, indole, isoflavonoids, linear esters and macrolides, peptides, phenolic derivatives, pyridine derivatives, pyrrole derivatives, quinones, and sterols. Their biological activities included anti-inflammatory, antimicrobial, anticancer, cytotoxic, and enzyme-inhibitory actions. In addition, the biosynthetic pathways of several potent bioactive compounds are summarized. Thus, lichen actinomycetes demonstrate exceptional abilities in the discovery of new drug candidates. [ABSTRACT FROM AUTHOR]

Chiral pyrrolic macrocycles continue to attract interest. However, their molecular design remains challenging. Here, we report a calixpyrrole‐based chiral macrocyclic system, calix[1]furan[1]pyrrole[1]thiophene (1), synthesized from an oligoketone. Macrocycle 1 adopts a partial cone conformation in the solid state, and undergoes racemization via ring inversion. Molecular dynamics simulations revealed that inversion of the thiophene is the rate determining step. Pyrrole N‐methylation suppressed racemization and permitted chiral resolution. Enantioselective N‐methylation also occurred in the presence of a chiral ammonium salt, although the stereoselectivity is modest. A unique feature of 1 is that it acts as a useful synthetic precursor to yield several calix[n]furan[n]pyrrole[n]thiophene products (n=2–4), including a calix[12]pyrrole analogue that to our knowledge constitutes the largest calix[n]pyrrole‐like species to be structurally characterized. [ABSTRACT FROM AUTHOR]

The insurgence in microbial resistance has led to urgent requirement of new and upgraded antimicrobial agents with new biological targets, higher potency, cost-effectiveness and low toxicity. The present work describes the synthesis and antimicrobial screening of some pyrrole 1,2,3-triazole hybrids bearing chalcone and amide scaffolds. The antimicrobial screening results revealed that all the synthesized pyrrole 1,2,3-triazoles (5a–5n) exhibited higher efficacy than the pyrrole-chalcones (2a–2b) towards the tested strains. Compounds 5k (MIC = 1.56 µg/mL) and 5l (MIC = 1.56 µg/mL) displayed highest potency toward E. coli which is equivalent to standard ciprofloxacin (MIC = 1.56 µg/mL). The docking of 5k within the active sites of E. coli DNA gyrase (PDB: 1KZN) and C. albicans sterol 14α-demethylase (PDB: 5TZ1) exhibited good interaction with binding energy of – 123.224 and – 114.278 kcal/mol, respectively [ABSTRACT FROM AUTHOR]

• Twelve examples of new pyrrole-tacrine hybrids are synthetized in yields up to 95 %. • Photophysical properties (λabs/λem) evaluated in solution by UV–Vis spectroscopy. • Noted emissions in the blue region (380–407 nm), SS (33–67 nm) and Φf up to 0.57. • Fluorescence lifetimes increase according to the solvent polarity (Toluene to DMF). This paper reports the synthesis, structural elucidation, and investigation of the photophysical properties of a novel heterocyclic system, such as pyrrole-hybridized polyhydro-spiro[chromeno[4,3- b ]cycloalka[4,5]thieno[3,2- e ]pyridine]cycloalkanes (3), where the spirocycloalkanes are cyclopentane, cyclohexane, and cycloheptane; and the cycloalka[4,5]thieno are cyclopenta-, cyclohexa-, and cyclohepta-. These hybrid scaffolds 3 resulted from N -derivatization reactions of a series of twelve examples of modified 7-amino-substituted precursors 1 , which, via the Clauson-Kaas reaction using 2,5-dimethoxy-tetrahydrofuran (2,5-DMOTHF) as a CCCC block, were applied to enable the construction and isolation of twelve mentioned pyrrole derivatives 3 in yields of 66 – 95 %. Compounds 3 were structurally fully characterized by melting point, 1H-, 13CNMR, and 1H13C– 2D-NMR (HSQC and HMBC) spectroscopy, X-ray diffraction, and HRMS analysis. The novel pyrroles 3 had their photophysical properties investigated (absorption and emission) in solution in several solvents. As a result, it was found that these pyrroles, where the transition bands were observed in the UV region, exhibit moderate luminescent and shorter lifetime decay values, which are related to and dependent on the spiromoiety and/or cycloalkanes directly fused to the thiophene ring of this new tacrine-modified system. [Display omitted] [ABSTRACT FROM AUTHOR]

A chemical study on the n-BuOH-soluble fraction of the 95% EtOH extract of rice fermented with the endophytic fungus Annulohypoxylon nitens has resulted in the isolation of one new natural pyrrole derivative, designated as nitenspyrrole (1), together with 3 known compounds, taraxasterol (2), oleanolic acid (3), and β-sitostenone (4). Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR experiments, and by ESI-MS. [ABSTRACT FROM AUTHOR]

Near‐infrared (NIR) fluorophores with characteristics such as deep tissue penetration, minimal damage to the biological samples, and low background interference, are highly sought‐after materials for in vivo and deep‐tissue fluorescence imaging. Herein, series of 3‐pyrrolylBODIPY derivatives and 3,5‐dipyrrolylBODIPY derivatives have been prepared by a facile regioselective nucleophilic aromatic substitution reaction (SNAr) on 3,5‐halogenated BODIPY derivatives (3,5‐dibromo or 2,3,5,6‐tetrachloroBODIPYs) with pyrroles. The installation of a pyrrolic unit onto the 3‐position of the BODIPY chromophore leads to a dramatic red shift of both the absorption (up to 160 nm) and the emission (up to 260 nm) in these resultant 3‐pyrrolylBODIPYs with respect to that of the BODIPY chromophore. Their further 5‐positional functionalization provides a facile way to fine tune their photophysical properties, and these resulting dipyrrolylBODIPYs and functionalized pyrrolylBODIPYs show strong absorption in the deep red‐to‐NIR regions (595–684 nm) and intense NIR fluorescence emission (650–715 nm) in dichloromethane. To demonstrate the applicability of these functionalized pyrrolylBODIPYs as NIR fluorescent probes for cell imaging, pyrrolylBODIPY 6 a containing mitochondrion‐targeting butyltriphenylphosphonium cationic species was also prepared. It selectively localized in mitochondria of HeLa cells, with low cytotoxicity and intense deep red fluorescence emission. [ABSTRACT FROM AUTHOR]

Light-activated polymerization is one of the most important and powerful strategies for fabrication of various types of advanced polymer materials. Because of many advantages, such as economy, efficiency, energy saving and being environmentally friendly, etc., photopolymerization is commonly used in different fields of science and technology. Generally, the initiation of polymerization reactions requires not only light energy but also the presence of a suitable photoinitiator (PI) in the photocurable composition. In recent years, dye-based photoinitiating systems have revolutionized and conquered the global market of innovative PIs. Since then, numerous photoinitiators for radical polymerization containing different organic dyes as light absorbers have been proposed. However, despite the large number of initiators designed, this topic is still relevant today. The interest towards dye-based photoinitiating systems continues to gain in importance, which is related to the need for new initiators capable of effectively initiating chain reactions under mild conditions. In this paper we present the most important information about photoinitiated radical polymerization. We describe the main directions for the application of this technique in various areas. Attention is mainly focused on the review of high-performance radical photoinitiators containing different sensitizers. Moreover, we present our latest achievements in the field of modern dye-based photoinitiating systems for the radical polymerization of acrylates. [ABSTRACT FROM AUTHOR]

The Paal-Knorr reaction of acetonylacetone with primary amines catalyzed by CATAPAL 200 under conventional heating at 60 °C for 45 min afforded N-substituted pyrroles in 68–97% yields. The pyrrole 3g was studied by single-crystal and powder X-ray diffraction. The high percentage of Brønsted–Lewis acid sites (23%) and pore diameter (37.8 nm) of CATAPAL 200 favor the formation of the pyrrole ring because an increase in Brønsted acid sites efficiently catalyzes condensation and dehydration processes. This protocol is distinguished by its operational simplicity, high yields, reduced reaction time, no solvent required, stoichiometric amounts of reactants, low catalyst loading, and clean reaction profile. In addition, the CATAPAL 200 is cheap and commercially available leading to an efficient and lower-cost chemical transformation. The reusability of the catalyst for up to five cycles without appreciable loss of its catalytic activity makes the present protocol sustainable and advantageous compared to conventional methods. [ABSTRACT FROM AUTHOR]

1,4‐Diphosphabarrelenes are bicyclic diphosphines relevant, for example, for the generation of polymetallic coordination compounds. However, current synthetic protocols either suffer from low yields or require multiple reaction steps. Herein, we report the one‐step synthesis of pyrrole‐based 1,4‐diphosphabarrelenes that are obtained in very good yields from the reaction of 1,2,5‐trimethylpyrrole with 1,2‐bis(dichlorophosphino)ethane or 1,2‐bis(dichlorophosphino)benzene. The new caged diphosphines are strong donor ligands and act as bridging ligand in nickel(0), rhodium(I), iridium(I) and copper(I) coordination compounds. [ABSTRACT FROM AUTHOR]

The formation of C−C bonds is a fundamental bond construction in organic synthesis. In this study, a highly active palladium catalytic system has been developed for the C2‐arylation of N‐acyl pyrroles with aryl halides in the help of copper additive and K2CO3. The reactions proceed smoothly under mild conditions and have excellent functional group compatibility. Especially, this protocol provides a straightforward method for the utilization of aryl chlorides in coupling reactions. A variety of valuable arylated N‐acyl pyrroles were synthesized and found to exhibit certain anti‐inflammatory activity. [ABSTRACT FROM AUTHOR]

A series of pyrrole derivatives and their antioxidant scavenging activities toward the superoxide anion (O2•−), hydroxyl radical (•OH), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH•) served as the training data sets of a quantitative structure–activity relationship (QSAR) study. The steric and electronic descriptors obtained from quantum chemical calculations were related to the three O2•−, •OH, and DPPH• scavenging activities using the genetic algorithm combined with multiple linear regression (GA-MLR) and artificial neural networks (ANNs). The GA-MLR models resulted in good statistical values; the coefficient of determination (R2) of the training set was greater than 0.8, and the root mean square error (RMSE) of the test set was in the range of 0.3 to 0.6. The main molecular descriptors that play an important role in the three types of antioxidant activities are the bond length, HOMO energy, polarizability, and AlogP. In the QSAR-ANN models, a good R2 value above 0.9 was obtained, and the RMSE of the test set falls in a similar range to that of the GA-MLR models. Therefore, both the QSAR GA-MLR and QSAR-ANN models were used to predict the newly designed pyrrole derivatives, which were developed based on their starting reagents in the synthetic process. [ABSTRACT FROM AUTHOR]

An efficient metal‐free, additive‐free synthetic method was developed to access benzooxepino‐fused pyrrole derivatives from alkynyl substituted aziridines. In this organic transformation, two new C−C bonds were formed via initial cleavage of C−C bond of aziridine ring by in situ generated azomethine ylides. Moderate to excellent yields of benzooxepino‐fused pyrroles were obtained atom economically in the presence of t‐BuOH in one‐pot. [ABSTRACT FROM AUTHOR]

Totally substituted butenolide including two tetrasubstituted olefins is a distinct structural motif seen in Stemona alkaloids, but efficient methods for its synthesis are not well developed. As an ongoing program aimed at the collective total synthesis of the stemoamide group, we report a stereodivergent method to give either (E)- or (Z)-totally substituted butenolide from the same intermediate. While AgOTf--mediated elimination via an E1-type mechanism results in the formation of the kinetic (Z)-tetrasubstituted olefin, subsequent TfOH-mediated isomerization gives the thermodynamic (E)-tetrasubstituted olefin. The pyrrole ring is another important structure found in Stemona alkaloids. The direct oxidation of pyrrolidine rings with MnO2 and careful purification gives the pyrrole groups without isomerization of the stereocenter in the lactone group. These two methods enabled us to synthesize a series of stemoamide-type alkaloids including tricyclic, tetracyclic, and pentacyclic frameworks. The anti-inflammatory activities by inhibition of iNOS expression in macrophage cell line RAW264.7 indicate that the most potent anti-inflammatory compounds without cytotoxicity are protostemonines, which consist of pentacyclic frameworks including the totally substituted butenolide. [ABSTRACT FROM AUTHOR]

Herein, the synthesis and X‐ray structures of three α,β "two wall" aryl‐extended calix[4]pyrroles having either identical (symmetrically substituted) or different (non‐symmetrically substituted) meso‐aryl substituents (aryl=4‐ethynylphenyl and 4‐iodophenyl) are reported. The X‐ray structure of the co‐crystal formed by the two symmetrically substituted calix[4]pyrroles is also described. In the solid state, all studied α,β‐calix[4]pyrroles exhibit a 1,3‐alternate conformation with two co‐crystallized acetonitrile solvent molecules H‐bonded to adjacent cis‐pyrrole rings. Remarkably, the 1,3‐conformer of the non‐symmetrically substituted iodophenyl/ethynylphenyl compound is intrinsically chiral. The two enantiomers are present in the average asymmetric unit in a 65 : 35 occupancy ratio displaying a head‐to‐tail directional disorder. This is due to the functional complementarity and the isosteric and isoelectronic properties of the para‐substituents: iodo and ethynyl. That is, the negative belt of iodine is similar to the negative π‐system of the C≡C triple bond and the σ‐hole in the iodine atom is similar to the positive proton at the C≡C−H group. [ABSTRACT FROM AUTHOR]

Antithrombotic agents based on factor XIIa inhibitors can become a new class of drugs to manage conditions associated with thrombosis. Herein, we report identification of two novel classes of factor XIIa inhibitors. The first one is triazolopyrimidine derivatives designed on the basis of the literature aminotriazole hit and identified using virtual screening of the focused library. The second class is a spirocyclic furo[3,4‐c]pyrrole derivatives identified by virtual screening of a large chemical library of drug‐like compounds performed in a previous study but confirmed in vitro here. In both cases, the prediction of inhibitory activity is based on the score of the SOL docking program, which uses the MMFF94 force field to calculate the binding energy. For the best ligands selected in virtual screening of the large chemical library, postprocessing with the PM7 semiempirical quantum‐chemical method was used to calculate the enthalpy of protein‐ligand binding to prioritize 16 compounds for testing in enzymatic assay, and one of them demonstrated micromolar activity. For triazolopyrimidine library, 21 compounds were prioritized for the testing based on docking scores, and visual inspection of docking poses. Of these, 4 compounds showed inhibition of factor XIIa at 30 μM. [ABSTRACT FROM AUTHOR]

Substituted pyrroles are prevalent aromatic ring systems encountered in numerous natural products and bioactive molecules. Herein, a novel ynamide scaffold has been designed, synthesized and subsequently applied to an unprecedented gold‐catalyzed and para‐toluenesulfonic acid (PTSA)‐assisted cascade cycloisomerization reaction for the synthesis of β‐pyrrole substituted α,β‐unsaturated ketones. Notably, the reaction is stereoselective, offering E‐isomer as major product with low to moderate yield. [ABSTRACT FROM AUTHOR]

A potential three component reaction strategy has been devised to generate nature inspired β-carboline N-fused pyrroles containing pyridine tethers. These scaffolds were afforded in high yields via a one-pot cascade regioselective reaction of diverse Kumujian C, 2-aminopyridines and alkyne derivatives under Cu(II)-catalysis. A library of 32 novel indolizino[8,7-b]indole derivatives with pyridine tethers has been developed. The current protocol offers excellent regioselectivity, high atom-economy and significant structural diversity. [ABSTRACT FROM AUTHOR]

Retrosine (RTS) is a pyrrolozidine alkaloid and a known hepatotoxin that widely exist in nature. The mechanisms involved in toxic action of pyrrolizidine alkaloids need further investigation. The objective of the present study was to evaluate the correlation of RTS hepatotoxicity with hepatic RTS concentration and pyrrole-protein adduction. Mice were intragastrically treated with RTS alone or RTS and ketoconazole (KTZ) simultaneously. Sera and liver tissues were collected at various time points after administration, followed by the determination of changes in serum transaminase activity, hepatic RTS concentration and pyrrole-protein adduction. The correlation of RTS hepatotoxicity with hepatic RTS concentration and hepatic pyrrole-protein adduction were examined by use of Sigmoid-Emax PK/PD models. Dose-dependent hepatotoxicity, hepatic RTS concentration and pyrrole-protein adduction were observed in the animals, which could be modulated by co-treatment with KTZ. The fit parameters indicated pyrrole-protein adduction was more closely related with liver injury than hepatic RTS concentration. Similar correlation was observed in mice given low-dose of RTS for 4 consecutive days. RTS hepatotoxicity is correlated with hepatic pyrrole-protein adduction derived from RTS rather than hepatic RTS concentration. The observed protein modification would be a good indicator to predict the hepatoxicity of RTS at low dose. [Display omitted] • Hepatic protein covalent binding was found to be closely associated with pyrrolizidine alkaloid-induced hepatotoxicity. • A PK/PD model was established to predict the hepatotoxicity induced by retrorsine after low-dose continuous administration. • Pyrrole-protein adduction is a sensitive and suitable indicator to reflect the liver toxicity induced by retrorsine. [ABSTRACT FROM AUTHOR]

A facile, catalyst‐ and solvent‐ free, three‐component reaction was developed for the synthesis of tetrasubstituted pyrroles at room temperature and under white light. The reaction proceeds via enamine formation between primary amines with 1,3‐dicarbonyl compounds followed by Michael addition with β‐nitro styrene and subsequent intramolecular cyclization and aromatization to yield 1,2,3,4‐tetrasubstituted pyrroles in good to excellent yields. Further, the present strategy is highly atom‐economical and environmentally benign. The preliminary in vitro cytotoxic studies on a set of compounds were performed against Hepatocellular carcinoma cells (HepG2) and one of the compounds 4 ac showed significant activity with an IC50 value of 17.82 μM. [ABSTRACT FROM AUTHOR]

Chemical diversification of substances present in natural product extracts can lead to a number of natural product-like compounds with a better chance of desirable bioactivities. The aim of this work was to discover unprecedented chemical conversion and produce new compounds through a one-step reaction of substances present in the extracts of marine sponges. In this report, a new unnatural tetracyclic bromopyrrole-imidazole derivative, rac-6-OEt-cylindradine A (1), was created from a chemically diversified extract of the sponge Petrosia (Strongylophora) sp. We also confirmed that 1 originated from naturally occurring (-)-cylindradine A (2) via a new reaction pattern. Moreover, (-)-dibromophakellin (3) and 4,5-dibromopyrrole-2-carboxylic acid (4), as well as 2, were reported herein for the first time in this genus. Studies on the possible reaction mechanism and bioactivities were also conducted. The results indicate that the direct chemical diversification of substances present in natural product extracts can be a speedy and useful strategy for the discovery of new compounds. [ABSTRACT FROM AUTHOR]

An efficient acid‐catalyzed synthesis of 1,5‐diaryl‐3‐(arylamino)‐1H‐pyrrol‐2(5H)‐ones is reported using novel N‐sulfonic acid modified poly (styrene‐diethylenetriamine) through three‐component reaction between aldehyde, amine, and ethyl pyruvate in high yields and short times. This heterogeneous solid catalyst is produced by reacting amine‐modified chloromethyl polystyrene with neat chlorosulfonic acid. The structure of the synthesized catalyst was examined with Fourier transform‐infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), dynamic light scattering (DLS), thermogravimetric analysis (TGA), differential thermal analysis (DTA), scanning electron micrograph (SEM), Brunauer–Emmett–Teller (BET), energy dispersive spectroscopy (EDS), and elemental analyses. The heterogeneous catalyst has many advantages, including an easy work‐up procedure, a high product yield, and the capability to be easily regenerated and reused for at least five cycles without losing its activity. [ABSTRACT FROM AUTHOR]

Starting from 5-(pyrrol-1-yl)pyrazole derivatives, the synthesis of triazole-based compounds by isosteric replacement of pyrrole and pyrazole was studied. The amido derivatives were obtained by organocatalyzed cycloaddition reactions between aryl azides and β-ketoamides or β-ketoesters. The synthesis of the second series of compounds, namely 5-(triazol-1-yl)pyrazole derivatives, involved the preparation of 5-azido-1H-pyrazole derivatives to be subjected to cycloaddition with alkynes. [ABSTRACT FROM AUTHOR]

In this work, a one‐pot three‐component reaction of ninhydrin, primary amines, and 1,3‐dicarbonyl compounds was investigated under various conditions to synthesis of diverse derivatives of dihydroindeno[1,2‐b]pyrroles. Catalyst‐free conditions in EtOH under ultrasound irradiation (45% of amplitude) were selected as a novel and efficient method for synthesis of these fused structures. The reactivity of different primary amines was then investigated for steric and electronic effects. Two examples of difunctional structures were also synthesized by using of 1,4‐diaminobenzene under optimum conditions with high yields. The structure of all products was characterized by spectroscopic methods and elemental analysis. [ABSTRACT FROM AUTHOR]

In this study, anion-responsive π-conjugated macrocycles were synthesized to demonstrate anion-binding and ion-pairing properties along with the ordered structures. Ion-pairing charge-by-charge assembly of a [1+2]-type complex of a macrocycle as a pseudo π-electronic anion and a countercation was revealed by single-crystal X-ray analysis. Further, two-dimensional (2D) arrays of the macrocycles bearing alkoxy chains, exhibiting anion-driven disordered structures, were constructed on a highly oriented pyrolytic graphite (HOPG) substrate as observed by scanning tunneling microscopy (STM)., (© 2025 The Author(s). Chemistry - An Asian Journal published by Wiley-VCH GmbH.)

Synthesis of N,N′-Di-Boc-2H-isoindole-2-carboxamidine, the first representative of isoindoles containing guanidine functionality, was carried out. The cycloaddition reactivity of this new Diels–Alder heterodiene was studied and the title compound was employed as a cycloaddition delivery reagent for guanidine functionality. Higher reactivity was found in comparison with the corresponding pyrrole derivative. Substitution with fluorine or guanidine functionality does not change the reactivities of isoindoles, and these findings are in good accord with computational results. [ABSTRACT FROM AUTHOR]

An efficient method for the synthesis of pharmaceutically and high-tech prospective 2-(3-amino-2,4-dicyanophenyl)pyrroles (in up to 88% yield) via the reaction of easily available substituted acylethynylpyrroles with malononitrile has been developed. The reaction proceeds in the KOH/MeCN system at 0 °C for 2 h. In the case of 2-acylethynylpyrroles without substituents in the pyrrole ring, the reaction changes direction: instead of the target 2-(3-amino-2,4-dicyanophenyl)pyrroles, the unexpected formation of pyrrolyldienols and products of their intramolecular cyclization, 3-amino-1-acylethylidene-2-cyanopyrrolizines, is observed. [ABSTRACT FROM AUTHOR]

A regioselective one-pot method for the synthesis of 1-ethyl 2,4-dihydrochromene[3,4-c]pyrroles in 63–94% yields from available 2-phenyl-, 2-trifluoro(trichloro)methyl- or 2-phenyl-2-(trifluoromethyl)-3-nitro-2H-chromenes and ethyl isocyanoacetate through the Barton–Zard reaction in ethanol at reflux for 0.5 h, using K2CO3 as a base, has been developed. [ABSTRACT FROM AUTHOR]

[Display omitted] • The first iron catalyzed cascade reaction for the synthesis of pyrroles from nitroarenes is reported. • A novel N, Si-codoped carbon-based iron catalyst for the solvent-free synthesis of pyrroles. • Iron single atomic sites (FeN x Si y) are the main catalytic active centers in this reaction. • The electron density of iron sites and Lewis acid sites of the catalyst are increased by Si doping. The development of novel iron heterogeneous catalysts for organic synthesis is attractive and significant for both academic and industrial applications. A carbon-based iron heterogeneous catalyst (Fe@NSiC) comprising of different iron species including iron atomic single sites (FeN x Si y), iron silicate and iron nanoparticles (NPs) has been developed. This catalyst exhibits high performance on the solvent-free synthesis of pyrroles from nitroarenes and 2,5-hexanedione via cascade reaction using HCOOH/DBU as the reductant. Si doping can increase Lewis acid sites of the catalyst and the electron density of iron sites, thus promoting the reaction. Furthermore, a set of pyrroles reflecting potential interest from the pharmaceutical perspective are obtained with moderate to excellent yields in this chemistry. [ABSTRACT FROM AUTHOR]

Heterocyclic compounds have a wide range of applications, and Pictet–Spengler reaction is effectual in the synthesis of heterocyclic compounds such as quinoline and isoquinoline. The present work describes an effective Pictet–Spengler-type protocol for the selective synthesis of quinoxaline derivatives from substituted pyrroles and diverse aromatic aldehydes over tailored SnO2 nanoparticles anchored multi-walled carbon nanotubes (SnO2@MWCNTs) nano-catalyst under greener reaction condition. An elementary reaction process (chemical synthesis) of oxidation of MWCNTs followed by uniform dispersion of SnO2 nanoparticles is used to synthesize the SnO2@MWCNTs catalyst. The SnO2@MWCNTs catalyst was then characterized by using modern spectroscopic and analytical techniques. The activity of catalyst was investigated toward the formation of selective quinoxaline. The reaction progressed with 100% conversion and 93–80% yield for the desired product at ambient operating conditions in just 2.30–3.30 h of reaction time. The effect of different parameters such as reaction temperature, time, and loading of SnO2 on MWCNTs, SnO2@MWCNTs catalyst loading were also investigated and discussed in detail. The protocol displayed high tolerance to different functionalities with respect to different substituted aromatic aldehydes to form quinoxaline derivatives in efficient way and gave excellent yield. Plausible reaction mechanistic pathway for the selective formation of quinoxaline over SnO2@MWCNTs is also proposed. It is believed that high dispersion of SnO2 over MWCNTs provided sufficient Lewis acidic sites for the reaction to selectively obtain the final product. Additionally, recyclability of SnO2@MWCNTs catalyst was also studied which demonstrated that the catalyst could be efficiently reused for six successive cycles without significant loss in its activity. The present work provides greener approach for synthesis of quinoxaline derivative preparation with high selectivity (free from oxidized quinoxaline as a side product) and efficient yield. [ABSTRACT FROM AUTHOR]

An efficient and facile iodine‐catalysed approach has been established for the formation of α‐substituted aryl ketones and valuable substituted naphthofurans. Under the same reaction conditions, a series of highly functionalized pyrroles could be readily obtained. This metal‐free and environmentally friendly reaction proceeded very well and delivered the products in good to excellent yields. This work highlights the formation of α‐substituted aryl ketones, naphthofuran and pentasubstituted pyrrole derivatives under catalytic amount of iodine in one‐pot fashion, demonstrating the broad substrate scope. [ABSTRACT FROM AUTHOR]

Using glucosamine hydrochloride as the starting material, 4‐(methoxycarbonyl)‐5‐methyl‐1‐propyl‐1H‐pyrrole‐2‐carboxylic acid (3) was initially created as an intermediate compound by cyclization and oxidation in order to create novel high temperature stable pyrrole compounds. Furthermore, Steglich esterification was used to produce N‐substituted pyrrole esters (4 a–4 t). All the new compounds were verified using nuclear magnetic resonance (1H and 13CNMR), infrared spectroscopy (IR), and high resolution mass spectrometry (HRMS). Thermogravimetry (TG), differential scanning calorimetry (DSC), and pyrolysis‐gas chromatography/mass spectrometry (Py‐GC/MS) techniques were used to examine the thermal behaviors of the compounds 4 f, 4 g, 4 i, and 4 q. Ester bonds from the pyrolysis products 4 g, 4 i, and 4 q might be severed which were consisted of the raw materials as well as the substrates, such as menthol, phenethyl and pyrrole derivatives which are commonly utilized in the sector of spices in foods and cigarette. [ABSTRACT FROM AUTHOR]

The perfluoroalkylthiolation reaction of indoles with perfluoroalkanesulfenic acids was achieved under mild conditions, while CH3COOH or TfOH was used as additive to promote the perfluoroalkylthiolation of activated benzene and pyrrole derivatives. A series of perfluoroalkylthiolated benzenes and heteroaromatic compounds were synthesized in moderate to good yields under transition‐metal‐free conditions. [ABSTRACT FROM AUTHOR]

A facile one‐pot multicomponent route for the synthesis of acenaphtho[1,2‐b] pyrroles from acenaphthenequinone using amines and activated alkynes is reported. The method involves the formation of a zwitterionic intermediate through Huisgen dipolar cycloaddition reaction of amines and activated alkynes. The solvent free method was found to be superior than conventional methods in terms of reaction resulted in excellent yields in the presence of electron releasing and halogen containing substituents on the primary aromatic amine and on altering the alkyl substituents of the acetylenic ester. Antioxidant activity of the titled derivatives (4a‐j) was investigated by the Diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging method. Compounds 4b and 4j showed relative radical scavenging potential comparable to that of ascorbic acid (IC50 = 25.20 μg/mL). Cell growth inhibition testing was carried out using 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay in two different human cancer cell lines colon (HT‐ 29) and breast (MCF‐7). Compound 4j is comparatively effective against HT‐29 cells (GI50 = 23.6 ± 0.11) in comparison with standard 5‐FU (GI50 = 25.5 ± 0.29) and also moderately effective against MCF‐7 cells (GI50 = 10.3 ± 0.12) in comparison with standard Doxorubicin (GI50 = 2.6 ± 0.06) among the other evaluated derivatives. The results revealed the promising lead compounds 4j for further optimization toward the discovery and development of new anti‐cancer agents. [ABSTRACT FROM AUTHOR]

The crystal and molecular structure of three derivatives of carbonyl 2-substituted pyrroles was determined by the single crystal X-ray diffraction. There are 2,2-dichloro-1-(1-methyl-1H-pyrrol-2-yl)ethan-1-one (I), 2-chloro-1-(1H-pyrrol-2-yl)ethan-1-one (II) and methyl 1H-pyrrole-2-carboxylate (III). All compounds crystallize with one molecule in the asymmetric unit in P212121 for I and II, and P21/c group for III. Despite the similar structures of the investigated compounds, the hydrogen bonds formed in their crystal structures adopt different H-bond motifs. In structure I, the dimers R12(5) and R21(7) form a chain along the b-axis, while in structures II and III, chain C(5) structural motifs are formed. The single point calculations at a ωB97XD/6-311++G(d,p) level of theory indicate that systems with N-H⋯O bonds have greater interaction energies (are more stable) compared with systems featuring C-H⋯O/Cl bonds. A descriptive Hirshfeld analysis showed that the greatest differences are visible for the H⋯H interactions. These H⋯H interactions predominate in structure III, accounting for 45% of the intermolecular interactions, while in structures I and II, they account for only 25%. Although compounds I-II contain Cl-atoms, the percentage of Cl⋯Cl interactions is rather low. In structure with two Cl-atoms (I), the contribution of the Cl⋯Cl contacts is 8.7% and for II, the contribution accounts for only 0.4% of the interactions. [ABSTRACT FROM AUTHOR]

Green synthesis design and spectroscopic characterizations of novel pyrrole derivatives (1–6) with insecticidal bioefficacy have been achieved. The toxic effect using a leaf dip bioassay method was used to assess the insecticidal bioefficacy of six ecofriendly‐synthesized pyrrole derivatives. The results demonstrated the significant insecticide effect of the proposed compounds against cotton aphids, after 24 hours of application. All these compounds (1–6) showed promising results against cotton aphids especially compound 4 with an LC50 of 0.04 ppm which had a higher activity compared to a commercial reference of Chlorfenapyr deadly agent used for cotton aphids. The biological activity profile of these compounds, using Trolox equivalent antioxidant capacity (TEAC) assay, antimicrobial activities against four gram‐positive bacteria, and antifungal activities against a yeast‐like fungus, in comparison with well‐known antimicrobial and antifungal referenced standards were evaluated and confirmed. The results revealed that some of these compounds showed antibacterial activities against bacterial species known to plant pathogenic. Additional investigation of the newly obtained derivatives was performed and discussed in this research work through computational tools to give better insights into the possible protein targets of these new analogues. [ABSTRACT FROM AUTHOR]

A survey of heterocyclic hemithioindigo photoswitches is presented identifying a number of structural motives with outstanding property profiles. The highly sought‐after combination of pronounced color change, quantitative switching in both directions, exceptional high quantum yields, and tunable high thermal stability of metastable states can be realized with 4‐imidazole, 2‐pyrrole, and 3‐indole‐based derivatives. In the former, an unusual preorganization using isomer selective chalcogen‐ and hydrogen bonding allows to precisely control geometry changes and tautomerism upon switching. Heterocyclic hemithioindigos thus represent highly promising photoswitches with advanced capabilities that will be of great value to anyone interested in establishing defined and reversible control at the molecular level. [ABSTRACT FROM AUTHOR]

Multi-substituted pyrroles are synthesized from regiospecific aziridine ring-opening and subsequent intramolecular cyclization with a carbonyl group at the γ-position in the presence of Lewis acid or protic acid. This method is highly atom economical where all the atoms of the reactants are incorporated into the final product with the removal of water. This new protocol is applied to the synthesis of various pyrroles, including natural products. [ABSTRACT FROM AUTHOR]

The article is devoted to heterocyclization of bis(2-chloroprop-2-en-1-yl)sulfide which proceeds in hydrazine hydrate–alkali medium and leads to formation of thiophene and pyrrole derivatives: previously described 4,5,9,10-tetrahydrocycloocta[1,2-c;5,8-c']dithiophene, as well as unknown hydrazone of 5-methylidene-3-methyldihydrothiophen-2-one and 1-amino-2-(propynylsulfanylpropenylsulfanyl)-3,5-dimethylpyrrole. Tentative mechanisms for the formation of the heterocyclic products are discussed. Obtained hydrazone of 5-methylidene-3-methyldihydrothiophen-2-one was used for the synthesis of a range of azine derivatives and in oxidation process with SeO2. The found reactions open up expedient approaches to the formation of various hardly accessible thiophene and pyrrole compounds from 2,3-dichloropropene and elemental sulfur as starting reagents. [ABSTRACT FROM AUTHOR]

Gold(I) chloride complex with triphenylphosphine and metal triflates catalyze the formation of novel [3,2‐b]pyrrole‐fused pentacyclic triterpenoids from accessible 2‐alkynyl derivatives of betulonic, ursonic and oleanonic acids. The reactions proceed in the presence of 5 mol% of the catalyst and provide pyrrole‐containing triterpenoids with the isolated yield of 60–86 %. [ABSTRACT FROM AUTHOR]

• A green, facile, and high-efficiency biocatalysis method synthesized 20 pyrrole derivatives in moderate to high yields. • This trypsin-catalyzed multi-component one-pot system has good universality. • Molecular simulations gained insight into trypsin preference for substrates and the intrinsic effect of solvents on this system. Multi-component reactions (MCRs) enable the development of efficient and atom-economic methods for synthesizing pyrrole derivatives. However, the current MCRs methods for synthesizing pyrrole derivatives in the enzymatic process have been unexploited. Herein, we developed a one-pot three-component enzymatic promiscuous catalytic system with green, efficient, and atom-economic to construct pyrrole derivatives. In this system, amines and 1,3-dicarbonyl compounds formed enamines with subsequent Michael addition with nitroolefins catalyzed by trypsin. A series of pyrrole derivatives were successfully obtained with moderate to good yield (up to 92 %). In addition, molecular simulations were conducted to gain insight into the source of differing tolerance of aromatic amides and fatty amines and the intrinsic effect of solvents in this system. This enzymatic catalytic one-pot three-component system has excellent functional tolerance, simple operation, and application potential for industrial production demonstrated by the gram scale experiment. [Display omitted] [ABSTRACT FROM AUTHOR]

A sustainable, metal-free, and highly efficient protocol for the synthesis of dihydroindeno[1,2-b]pyrrole derivatives via a tandem one-pot three-component reaction in aqueous medium at room temperature using an effective and reusable mesoporous heterogeneous organocatalyst, MPC@But-SO 3 H has been developed. MPC@But-SO 3 H was easily synthesized using a melamine-based covalent organic polymer and 1,4-butane sultone. The organocatalyst was well characterized by numerous spectroscopic techniques such as Fourier Transform Infrared (FTIR), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS), Powder X-ray diffraction (PXRD), Scanning Electron Microscope (SEM), Energy Dispersive X-ray (EDX), elemental mapping, and Thermal Gravimetric (TG) analyses. The catalyst displayed excellent catalytic potential, high thermochemical stability, and reusability for up to eight catalytic cycles. It offered the title compounds in excellent yields (˃90%) in a short reaction time (9-14 min). The synthesized compounds were characterized through FTIR, 1H, and 13C Nuclear Magnetic Resonance (NMR), and the molecular structure of 2-(benzylamino)-3a,8b-dihydroxy-1-methyl-3-nitro-3a,8b-dihydroindeno[1,2-b]pyrrol-4(1H)-one (4a) was confirmed by the Single Crystal XRD (SC-XRD) analysis. The key features of the present protocol include the use of water as a green solvent, zero involvement of any metal, sustainable reaction conditions, easy catalyst recovery, and a simple work-up procedure. The calculations for green metrics parameters further supported the greenness and sustainability of the protocol. [Display omitted] • A mesoporous heterogeneous organocatalyst, MPC@But-SO 3 H was developed using a melamine-based COP and 1,4-butane sultone. • MPC@But-SO 3 H-catalyzed highly efficient protocol was developed for synthesizing dihydroindeno[1,2-b]pyrrole derivatives. • The sustainable and metal-free protocol involves water as a green solvent and operates at room temperature. • Easy catalyst recovery and a simple work-up procedure are the key features of the present protocol. • The calculations for green metrics parameters supported the greenness and sustainability of the protocol. [ABSTRACT FROM AUTHOR]