Pyrrole Derivatives Research Articles

Electrochemical Cyclization of Alkynyl Enaminones: Controllable Synthesis of Indeno[1,2-c]pyrroles or Indanones.

We report an electrochemical intramolecular [3 + 2] cyclization of alkynyl enaminones in a user-friendly undivided cell under constant current conditions without an oxidant and catalyst, and indeno[1,2-c]pyrrole derivatives could be obtained in good to excellent yields. Notably, preliminary substituent-controlled selective transformation is also achieved under electrocatalysis alone, and indeno[1,2-c]pyrrole (R4 ≠ H) or indanone derivatives (R4 = H) could be prepared directly under electrocatalysis without adding a base and heating process.

Aggregation Modes of Chiral Diketopyrrolo[3,4-c]pyrrole Dyes in Solution and Thin Films.

The chiroptical features of chiral diketopyrrolo[3,4‐c]pyrrole (DPP) derivatives have been only marginally investigated to date. In this regard, we have synthesized ad hoc four chiral DPP dyes, functionalized with enantiopure alkyl groups from natural sources either on the lactam moieties or on the terminal positions of the π‐conjugated backbone, to promote an efficient self‐assembly into chiral supramolecular structures. For each of them, the aggregation modes has been investigated by absorbance and ECD spectroscopies in conditions of solution aggregation and on thin films, considering the effects of deposition technique (drop casting vs. spin coating) and post‐deposition operations (solvent and thermal annealing). The effect of the structure of lateral π‐conjugated units attached to the central DPP scaffold, as well as that of the position of the alkyl chiral group, has been assessed. ECD revealed superior capability, compared to absorbance spectroscopy, to provide information on the aggregation modes and to detect the possible co‐existence of multiple aggregation pathways.

Palladium(II)-Catalyzed [2+2+1] Annulation of Alkynes and Hydroxylamines: A Rodox-Neutral Approach to Fully Substituted Pyrroles.

A palladium-catalyzed [2+2+1] annulation of alkynes and hydroxylamines has been developed for the rapid construction of fully substituted pyrroles. This transformation involves sequential nucleophilic-addition of hydroxylamine to alkyne, alkyne migratory insertion, and synergistic demetallization cyclization, which provides a redox-neutral annulation approach to pyrrole derivatives. Moreover, the strategy enabled alteration of the photophysical properties of pyrrole products by varying the aryl substituents, thus leading to the development of N-functionalized tetraarylpyrroles as new fluorophores.

Simple Dipyrrin Analogues of Prodigiosin for Use as Colistin Adjuvants.

Multidrug resistant (MDR) bacteria are an increasing public health problem. One promising alternative to the development of new antibiotics is the use of antibiotic adjuvants, which would allow the continued use of FDA-approved antibiotics that have been rendered ineffective due to resistance. Herein, we report a series of dipyrrins and pyrrole derivatives designed as analogues of prodigiosin and obatoclax, several of which potentiate the activity of colistin against Klebsiella pneumoniae, with lead compounds also potentiating colistin against Acinetobacter baumannii and Pseudomonas aeruginosa.

Endoplasmic Reticulum Stress-Induced Apoptotic Effects of Novel 1-Pyrroline (3,4-Dihydro-2H-pyrrole) Derivatives on Breast Cancer Cells.

Heterocyclic compounds have emerged as promising and appealing scaffolds for developing effective antitumor agents. Here, the effects of synthesized 24 different 1-pyrroline derivatives (PDs) containing substituted aryl sulfide moiety were investigated on human breast cancer cell lines. The viability of cells was assessed via MTT assay. Reactive oxygen species (ROS) generation was analyzed via fluorescent dye CM-H2DCFDA. Apoptotic cells were determined via flow cytometry. Endoplasmic reticulum (ER) stress-associated protein levels were analyzed via western blot analysis. Four of the PDs (PD-12, -14, -16 and -17) had great cytotoxic selectivity against breast cancer cells. Apoptotic cell death was induced by PDs via the generation of ROS. PDs significantly increased the GRP78, p-PEAK, p-eIF2α, and CHOP protein levels indicating ER stress in breast cancer cells. These results imply that newly synthesized PDs may be potential anticancer agents as they selectively inhibit breast cancer cells.

The LAM of the Rings: Large Amplitude Motions in Aromatic Molecules Studied by Microwave Spectroscopy.

Large amplitude motions (LAMs) form a fundamental phenomenon that demands the development of specific theoretical and Hamiltonian models. In recent years, along with the strong progress in instrumental techniques on high-resolution microwave spectroscopy and computational capacity in quantum chemistry, studies on LAMs have become very diverse. Larger and more complex molecular systems have been taken under investigation, ranging from series of heteroaromatic molecules from five- and six-membered rings to polycyclic-aromatic-hydrocarbon derivatives. Such systems are ideally suited to create families of molecules in which the positions and the number of LAMs can be varied, while the heteroatoms often provide a sufficient dipole moment to the systems to warrant the observation of their rotational spectra. This review will summarize three types of LAMs: internal rotation, inversion tunneling, and ring puckering, which are frequently observed in aromatic five-membered rings such as furan, thiophene, pyrrole, thiazole, and oxazole derivatives, in aromatic six-membered rings such as benzene, pyridine, and pyrimidine derivatives, and larger combined rings such as naphthalene, indole, and indan derivatives. For each molecular class, we will present the representatives and summarize the recent insights on the molecular structure and internal dynamics and how they help to advance the field of quantum mechanics.

Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors.

In order to find potential inhibitors of tyrosinase, two series of pyrrole derivatives A (1–17) and B (1–8) were synthesized and screened for their inhibitory activities on tyrosinase. Most of the 2-cyanopyrrole derivatives exhibited effective inhibitory activities. In particular, A12 exhibited the strongest inhibitory activities, with the IC50 values of 0.97 μM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC50: 28.72 μM). The inhibitory mechanism analysis results revealed that A12 was a reversible and mixed-type inhibitor. Molecular docking experiments clarified the interaction between A12 with tyrosinase. Furthermore, A12 (100 μM) presented effective inhibitory effect on tyrosinase in B16 melanoma cells with inhibition of 33.48%, which was equivalent to that of Kojic acid (39.81%). Accordingly, compound A12 may serve as the lead structure for the further design of potent tyrosinase inhibitors. Molecular docking studies confirmed the interaction between the compound and tyrosinase.

Development of a palladium-catalyzed decarboxylative arene cross-coupling of pyrrole derivatives in a flow reactor

Development of a palladium-catalyzed decarboxylative arene cross-coupling of pyrrole derivatives in a flow reactor

Synthesis of New Fused 4H-Thieno[3,2-b]pyrrole Derivatives via Decomposition of Methyl 4-Azido-5-arylthiophene-2-carboxylates

AbstractThis article is focused on the development of practical approaches to the synthesis of 4-azido-5-arylthiophene-2-carboxylates and 4-amino-5-arylthiophene-2-carboxylates using the Fiesselmann reaction. The photochemical and thermal (including microwave-assisted) decomposition of 4-azido-5-arylthiophene-2-carboxylates have been studied in order to synthesize fused 4H-thieno[3,2-b]pyrrole derivatives. The proposed approaches allow to obtain functionally substituted heteroacenes, which are of interest as building blocks for organic semiconductors.

Synergistic Pd/Cu Catalyzed Allylation of Cyclic Ketimine Esters with Vinylethylene Carbonates: Enantioselective Construction of Trisubstituted Allylic 2H‐Pyrrole Derivatives

AbstractAn asymmetric allylation of cyclic ketimine esters with vinylethylene carbonates was accomplished through a Pd/Cu dual catalysis system under a mild condition, providing a range of trisubstituted allylic 2H‐pyrrole analogues bearing a chiral quaternary stereogenic center in high yields (up to 92% yield) and with excellent regioselectivities and enantioselectivities (up to 96% ee). A gram‐scale operation was also conducted in high efficiency without erosion of enantioselectivity and stereoselectivity.magnified image

Front Cover Picture: Synergistic Pd/Cu Catalyzed Allylation of Cyclic Ketimine Esters with Vinylethylene Carbonates: Enantioselective Construction of Trisubstituted Allylic 2H‐Pyrrole Derivatives (Adv. Synth. Catal. 11/2022)

The front cover image, provided by Fener Chen, illustrates an asymmetric allylation of cyclic ketimine esters with vinylethylene carbonates through a Pd/Cu dual catalysis system under a mild conditions. This protocol provides a range of trisubstituted allylic 2H-pyrrole analogues bearing a chiral tetrasubstituted stereogenic center in high yields and with excellent regioselectivities and enantioselectivities. A gram-scale operation was also conducted in high efficiency without erosion of enantioselectivity and stereoselectivity. Details can be found in the communication by Fener Chen and co-workers (M. Ke, Y. Yu, K. Zhang, S. Zuo, Z. Liu, X. Xiao, F. Chen, Adv. Synth. Catal. 2022, 364, 1849–1854; DOI: 10.1002/adsc.202200039).

Synthesis of Spiropyrazoles Under Organic and Nonorganic Catalysis

Abstract: Spiropyrazoles display many biological activities such as antitumor, vasodilation, analgesic, phosphodiesterase inhibitors, aldosterone antagonistic, anabolic, androgenic, antiinflammatory, progestational and salt-retaining activities, and they also exert neuroprotection in dopaminergic cell death. Many efforts have been made to obtain these derivatives with high yield and excellent regio-, diastereo- and enantioselectivities. Most of the spiroprazole synthesis methods were proceeded in good to excellent yield in the presence of organic catalysts, such as squaramide, NHC pre-catalyst, pyrrole derivatives, bis-oxazoline, etc. DMAP, DABCO, thiourea derivatives, DBU, acetic acid and quinoline catalysts. In addition, the inorganic and organometallic catalysts have been proven their efficiency in the synthesis of various types of spiro-pyrazoles in excellent yield. Thus, in this review, we have compiled all citations for the synthesis of spiropyrazoles in the presence of various types of catalysts such as organic, inorganic, and metalorganic catalysts in the range 2020 to 2012. This review article is a useful compilation for researchers interested in the synthesis of spiropyrazole derivatives and will assist them in selecting appropriate catalysts for the preparation of their spiropyrazoles.

Cyclopentenedione-based ascorbate-rejecting permselective layers prepared by electropolymerization

This work focuses on the preparation and optimization of organic functional layers based on 4-cyclopentene-1,3-dione. Hybrid molecules composed of 4-cyclopentene-1,3-dione anchored to a polymerizable moiety based either on pyrrole or methoxybenzene derivatives were synthesized and used for the preparation of thin films by electropolymerization. It is shown that the cyclopentenedione-containing films suppress the ascorbate (negatively charged) electrochemical response when deposited on glassy carbon electrodes, while the response connected to dopamine (positively charged) electrooxidation remains unaffected or is only slightly suppressed. The ascorbate-dopamine selectivity was studied in detail by voltammetry with stationary and rotating disk electrodes.

TiO2-coated graphene oxide-molybdate complex as a new separable nanocatalyst for the synthesis of pyrrole derivatives by Paal-Knorr reaction

The preparation of chemical and pharmaceutical compounds through organic reactions has always been associated with the production of environmental waste. Growth population and concerns about ecological pollution increase the interest in using heterogeneous solid catalysts with capabilities such as increasing reaction efficiency and reducing the production of by-products, as well as the ability to separate and reuse. To develop and benefit such catalysts as much as possible, in this study, using graphene oxide (GO) as a support, we succeeded in preparing a heterogeneous catalyst with a high contact surface, excellent performance, and recyclability. Graphene oxide nanosheets were synthesized according to Hummer’s method. hexamolybdate anions ([n-Bu 4 N] 2 [Mo 6 O 19 ]) were placed on this support as a catalytically active site using linkers. The structure of this catalyst was confirmed by XRD, FT-IR, EDS, SEM, TEM, TGA, Raman, and nitrogen adsorption–desorption analyses, and it was used to produce pyrroles by the Paal-Knorr method. The performance of the synthesized nanocatalyst was satisfactory for all the derivatives studied. Recovery and reuse of GO@TiO 2 @(CH 2 ) 3 N = Mo[Mo 5 O 18 ] after catalytic reactions were examined. This catalyst could be quickly recovered by simple filtration and recycled ten times without significant loss of its catalytic activity.

Separation of Mercury(II) from Industrial Wastewater through Polymer Inclusion Membranes with Calix[4]pyrrole Derivative.

Polymer membranes with immobilized ligands are encouraging alternatives for the removal of toxic metal ions from aquatic waste streams, including industrial wastewater, in view of their high selectivity, stability, removal efficacy and low energy demands. In this study, polymer inclusion membranes (PIMs) based on cellulose triacetate, with a calix[4]pyrrole derivative as an ion carrier, were tested for their capability to dispose mercury (Hg(II)) ions from industrial wastewater. The impacts were assessed relative to carrier content, the quantity of plasticizer in the membrane, the hydrocholoric acid concentration in the source phase, and the character of the receiving phase on the performance of Hg(II) elimination. Optimally designed PIMs could be an interesting option for the industrial wastewater treatment due to the high removal efficiency of Hg(II) and great repeatability.

Photoinduced 6π-Electrocyclization of 1,3,5-hexatriene system containing allomaltol fragment: A convenient approach to polycondensed pyrrole derivatives

An efficient photochemical approach was developed for the synthesis of benzo[e]pyrano[3,2-g]indoles. The presented method is based on 6π-electrocyclization of terarylenes containing pyrrole and allomaltol fragments. Various options for increasing the regioselectivity of the proposed approach, including both chemical modification of the allomaltol moiety and the use of certain conditions that block side processes were suggested. Advantages of this method are the employment of readily accessible starting materials, operational simplicity and easy isolation of the target products avoiding chromatographic purification. It was demonstrated that the considered photoreaction of allomaltol derivatives can be employed for the photoacid generation. The structure of one of the synthesized photoproducts was established by X-ray diffraction.

Structural diversity using amino acid “Customizable Units”: conversion of hydroxyproline (Hyp) into nitrogen heterocycles

The ability of amino acid “customizable units” to generate structural diversity is illustrated by the conversion of 4-hydroxyproline (Hyp) units into a variety of nitrogen heterocycles. After a first common step, where the unit underwent a one-pot decarboxylation–alkylation reaction to afford 2-alkylpyrrolidines with high stereoselectivity, a divergent step was carried out. Thus, the deprotected 4-hydroxy group was used either to initiate a radical scission that afforded aliphatic β-amino aldehydes, or to carry out an elimination reaction, to give 2-alkyl-2,5-dihydro-1H-pyrroles. In the first case, the amines underwent a tandem reductive amination–cyclization to afford β-amino-δ-lactams, an efficient rigidifying unit in peptides. Different lactam N-substituents, such as alkylamines, peptides, and alkenyl chains suitable for olefin metathesis were introduced this way. In the second case, the pyrrole derivatives were efficiently converted into alkaloid and iminosugar derivatives in good global yields and with excellent stereoselectivity.

Novel edifice calix[4]pyrrole derivatives as a potential sensor for the detection of analytes and in silico computational behaviour

The beguiling properties of functionalised calix[4]pyrrole has garnered a lot of attention due to its selective and specific sensitivity towards biomolecules and cations, it behaves as a frontline contender for recognition moieties and their eventual applications as fluorogenic sensing agents have received increasing interest. The binding properties of calix[4]pyrrole can be modulated by diverse structural modifications or by the change of solvent. Accessibility, high fluorescence quantum yield, and biological activity of aminoanthraquinone and aminoquinoline has attracted as a fluorophore, polymer additives and medicinal agents. Due to the tunable properties of aminoanthraquinone and aminoquinoline and calix[4]pyrrole scaffold fixing up may lead to development of new sensor. In this regards we have synthesised two derivatives of calix[4]pyrrole bearing carboxylic group i.e. ABCPTAA & ABCPTAQ which binds selectively with OTC and Hg(II) ions, respectively. The experimental data are very well supported by spectroscopic as well as computational studies.

Dual Role of the Arylating Agent in a Highly C(2)-Selective Pd-Catalysed Functionalisation of Pyrrole Derivatives

AbstractPyrrole derivatives with C(2)-aryl substituents are an important and widespread class of heterocyclic compounds. Their synthesis can be accomplished using several strategic variants which usually entail either protection of the N–H functionality followed by the arylation, or a direct arylation. Although direct arylation is a preferable process due to a reduced number of synthetic steps, it often requires vigorous conditions or challenging reagents. To this synthetic repertoire, we add a novel method that is based on the dual role of the arylating agent. It serves as the nitrogen protecting group while also being involved in the arylation step. Deprotection as a final stage is carried out simultaneously utilising amines as reacting components. This approach ensures relatively mild conditions and exclusive C(2) selectivity yielding 2-arylpyrroles with the amide functionality. While aromatic amines are not suitable partners under studied conditions, most likely due to lower nucleophilicity, aliphatic amines, either primary or secondary, afford products in good yields.

4D-QSAR Analysis of Some New Pyrrole Derivatives Using Klopman Index Descriptor

We applied the Klopman Index, the Local Reactive Descriptor (LRD), for 3-Dimensional (3D) interactions between the Ligand-Receptor (L-R), for some new pyrrole derivatives as antituberculosis agents for 4-Dimensional Quantitative Structure-Activity Relationship (4D-QSAR) investigations. The parameters of the receptor side belonging to the Pharmacophore (Pha), which consists of the interaction points suggested between L-R, were calculated in the Molecular Conformer Electron Topological (MCET) method we developed based on the LRD values on the ligand side. After the 4D-QSAR model was established with the Leave One Out Cross-Validation (LOO-CV) technique on the molecules in the training set, the model was confirmed on the molecules in the external test set. Statistical results obtained from both sets, Q2 = 0.875 and Rext2 = 0.918, respectively, were evaluated as satisfactory.