Polycyclic Derivatives Research Articles

Efficient synthesis of novel phenanthroline-dimedone derivatives using Pd@HQBI-SPION as a versatile palladium-immobilized catalyst

This paper presents the synthesis and application of a novel catalyst for carbon–carbon bond formations, comprising palladium immobilized on 2-(5-hydroxyquinolin-8-yl)-1H-benzo[d]imidazole-5-carboxylic acid modified superparamagnetic iron oxide nanoparticles (Pd@HQBI-SPION). The synthesis involved the attachment of HQBI ligands to SPION using APTES, followed by the immobilization of palladium. Characterization techniques, including FTIR, TEM, and magnetic measurements, confirmed the successful synthesis and structural integrity of Pd@HQBI-SPION. The catalytic activity of Pd@HQBI-SPION was evaluated in various carbon–carbon bond formation reactions, demonstrating high efficiency and reusability. 8 different derivatives bearing several electron withdrawing and electron donating functionalities were used as starting materials and the products were obtained in high isolated yields (75–97%). The catalyst exhibited excellent performance in one-pot synthesis of phenanthroline-dimedone polycyclic derivatives via C-alkylation followed by intramolecular O-alkylation of phenanthroline with dimedone. The products are obtained in high to excellent yields is described. This protocol presents a highly selective synthetic method for the construction of polycyclic aromatic compounds containing nitrogen and oxygen atoms.

Structural and Electronic Factors Controlling the Efficiency and Rate of Intersystem Crossing to the Triplet State in Thiophene Polycyclic Derivatives.

Thiophene polycyclic derivatives are widely used in organic light-emitting diodes, photovoltaics, and medicinal chemistry applications. Understanding the electronic and structural factors controlling their intersystem crossing rates is paramount for these applications to be successful. This study investigates the photophysical, electronic structure, and excited state dynamics of 1,2-benzodiphenylene sulfide, benzo[b]naphtho[1,2-d]thiophene, and benzo[b]naphtho[2,3-d]thiophene in polar aprotic and non-polar solvents. Steady-state absorption and emission spectroscopy, femtosecond transient absorption spectroscopy, and DFT and TD-DFT calculations are employed. Low fluorescence quantum yields of 1.2 to 2.7 % are measured in acetonitrile and cyclohexene, evidencing that the primary relaxation pathways in these thiophene derivatives are nonradiative. Linear interpolation of internal coordinates calculations predict that an S-C bond elongation reaction coordinate facilitates the efficient intersystem crossing to the T1 state. Excitation of 1,2-benzodiphenylene sulfide and benzo[b]naphtho[1,2-d]thiophene at 350 nm or benzo[b]naphtho[2,3-d]thiophene at 365 nm, populates the lowest-energy 1ππ* state, which relaxes to the 1ππ* minimum in tens of picoseconds or intersystem crosses to the triplet manifold in ca. 500 ps to 1.1 ns depending on the position at which the benzene rings are added. Excitation at 266 nm does not affect the intersystem crossing rates. Laser photodegradation experiments demonstrate that the thiophene polycyclic derivatives are highly photostable.

1,3-Dipolar Cycloaddition of Nitrile Oxides and Nitrilimines to (-)-β-Caryophyllene: Stereoselective Synthesis of Polycyclic Derivatives and Their Biological Testing.

The cycloaddition of nitrile oxides and nitrilimines to one or both of the C=C double bonds of caryophyllene is described. The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrilimines to caryophyllene was demonstrated. As a result of these reactions, pharmacophore fragments of isoxazoline and pyrazoline are introduced into the structure of caryophyllene, which leads to an increase in the conformational rigidity of the molecule. A complete stereochemical assignment of 1,3-dipolar cycloaddition adducts to caryophyllene was carried out. The study of antiviral and cytotoxic activity for some heterocyclic derivatives synthesized in this work revealed relatively high biological activity of previously little-studied cycloaddition adducts at the exocyclic C=CH2 bond of caryophyllene. The effect of substituents in the synthesized heterocycles on biological activity was demonstrated. Compounds with a good inhibitory effect on the H1N1 influenza virus were revealed. The activity of the compound was demonstrated up to 6 h post infection, and this could be due to slight inhibiting activity against viral neuraminidase, necessary at the stage of progeny virion budding.

Design and synthesis of novel main protease inhibitors of COVID-19: quinoxalino[2,1-b]quinazolin-12-ones.

The COVID-19 pandemic represents a substantial global challenge, being a significant cause of mortality in numerous countries. Thus, it is imperative to conduct research to develop effective therapies to combat COVID-19. The primary aim of this study is to employ a two-step tandem reaction involving 2,3-dichloroquinoxaline and 2-amino-N-substituted benzamides in alkaline media/DMF at an elevated temperature to design and synthesize a series of polycyclic derivatives endowed with quinoxalino[2,1-b]quinazolin-12-one framework. Following synthesis, the newly synthesized heterocycles were evaluated for their potential as inhibitors of the main protease of SARS-CoV-2 by means of molecular docking and dynamic simulation techniques. The in silico investigation demonstrated that all tested compounds effectively establish stable binding interactions, primarily through multiple hydrogen bonding and hydrophobic interactions, at the active site of the enzyme. These findings offer crucial structural insights that can be employed in future endeavors toward designing potent inhibitors targeting the main protease (Mpro). Among the investigated compounds, the p-tolylamino-substituted quinoxalino[2,1-b]quinazolinone derivative exhibited the most promise as an inhibitor of the main protease in COVID-19. Consequently, it warrants further investigation both in vitro and in vivo to identify it as a prospective candidate for anti-SARS-CoV-2 drug development.

Visible‐Light‐Induced Copper‐Catalyzed Alkylation/exo‐Cyclization of 1,7‐Dienes with Sulfonium Salts to Access Sulfur‐Containing Polycyclic Compounds

AbstractA direct visible‐light‐promoted radical‐triggered tandem cyclization of 1,7‐diene systems with cyclic sulfonium salts by using copper(I)‐based complexes as photoredox catalyst is developed. With this approach, a variety of sulfur‐containing polycyclic derivatives are prepared through alkylation/6‐exo‐trig cyclization/5‐exo‐trig cyclization of 1,7‐diene systems under mild conditions. In addition, the photoinduced copper‐catalyzed ring‐opening of cyclic sulfonium salts provides the alkyl radical intermediates, which prefers addition to the C−C double bond that connected to the aromatic ring rather than the electron‐deficient vinyl in 1,7‐dienes. Moreover, oxidation of the desired sulfur‐containing polycyclic products provides a strategy for the preparation of remote nitrogen‐fused polycyclic substituted sulfoxide or sulfone‐containing derivatives.

Synthesis of Acylation Polycyclic Derivatives via Regioselective Acylation/Cyclization of 1,7-Dienes with Acyl Oxime Esters.

A visible-light-induced radical cascade regioselective acylation/cyclization of 1,7-dienes with acyl oxime esters for the preparation of acylation polycyclic compounds via NCR-mediated C-C σ-bond cleavage is established. The transformation involves the cleavage of the C-C σ-bond in acyl oxime esters and selective addition of the electron neutral C═C bonds in 1,7-dienes for the synthesis of acyl polycyclic quinolinone derivatives, not the traditional seven-membered ring products. The strategy offers several advantages, including broad substrate tolerance, no need for bases, hyperstoichiometric radical initiators, and other auxiliaries.

Recent Advances in Manganese(III)-Assisted Radical Cyclization for the Synthesis of Natural Products: A Comprehensive Review.

Natural products play an important part in synthetic chemistry since they have many pharmacological properties and are used as active drug compounds in pharmaceutical chemistry. However, synthesis of these complex molecules is difficult due to the requirement of various synthetic steps, which include highly regio- and stereoselectivity. Therefore, oxidative radical cyclization assisted by manganese(III) acetate serves as an important step in obtaining spiro-, tricyclic, tetracyclic, and polycyclic derivatives of these compounds. Manganese(III)-based reactions offer a single-step regio- and stereoselective cyclizations and α-acetoxidations, reducing the number of synthetic steps. Also, the manganese(III)-mediated oxidative free radical cyclization method has been successfully applied for the synthesis of cyclic structures found in many natural products. This article presents a broad overview of manganese(III)-based radical reactions of natural products as a key step in overall synthesis. The authors have classified natural product synthesis processes assisted by manganese(III) acetate as intermolecular, intramolecular, oxidation, acetoxidation, aromatization, and polymerization reactions, respectively.

Assessment of the Impact of Polycyclic Derivatives of the Frame Series on the Replicative Properties of the SARS-CoV-2 Virus in an <I>in vitro</I> Experiment

The aim of the work was to determine the cytotoxicity and the influence of polycyclic derivatives of the framework series on the replicative properties of the SARS-CoV-2 virus in Vero-E6 cell culture in vitro. Materials and methods. The virus inhibiting effect of 50 adamantane and bicyclo[3.3.1]nonane derivatives with carbocyclic and heterocyclic substituents was investigated. The studies were carried out on Vero-E6 cell culture by assessing the cytopathic effect of the virus. The impact of the compounds on the replicative properties of the SARS-CoV-2 virus was estimated by the decrease in virus titer in the presence of the compounds compared to the control. Based on the virus titer values in the presence of a series of successively decreasing concentrations of the compound, the 50 % effective concentration was calculated.Results and discussion. A study of polycyclic derivatives of the framework series has identified two compounds with antiviral properties against the SARS-CoV-2 virus. Among bicyclo[3.3.1]nonane derivatives containing heterocyclic fragments, compound No. 15144 has showed an inhibitory effect against the SARS-CoV-2 virus. The protective effect of the compound was manifested in maximum tolerable concentration (MTC) (70.0 μg/ml) and ½ MTC (35.0 µg/ml). A decrease in virus titers under the influence of MTC by 0.95 lg TCD50/ml, in ½ MTC (35.0 μg/ml) – by 0.35 lg TCID50/ml has been detected. The effective concentration (EC50) value of the compound No. 15144 was 64.0 μg/ml, the MTC/EC50 ratio was 1.09. Compound No. 14838 (adamantane derivative containing carbocyclic fragments) had less pronounced antiviral activity. As a result of research, it has been established that sample No. 14838 at a dose of MTC (45.0 μg/ml) reduces the infectious titer by 0.78 lg TCD50/ml, in ½ MTC (22.5 μg/ml) by 0.15 lg TCD50/ml compared to the control. The EC50 value of compound No. 14838 was 37.0 μg/ml, the MTC/EC50 ratio was 1.22.

Photoinduced 1,3‐Dipolar Cycloadditions of Cyclic Enones and 2,5‐Disubstituted Tetrazoles: An Unprecedented Pathway to Polysubstituted Pyrazolines and Pyrazoles

AbstractWe report herein the syntheses of original pyrazolines and pyrazoles through 1,3‐dipolar cycloaddition of cyclic enones with 2,5‐disubstituted nitrile imines achieved via photochemical activation of 2,5‐diaryl substituted tetrazoles. Monitoring of the reactions, similar to nitrile imine‐mediated tetrazole‐ene cycloadditions (NITEC), could be performed by means of UV‐vis absorption and emission measurements. The presence or absence of substituents in the alpha position of the ketone function makes it possible to direct these reactions towards the selective formation of pyrazoles or pyrazolines. The choice of the cyclic enones and 2,5‐disubstituted tetrazoles proved crucial for the fluorescence properties of the polycyclic derivatives obtained.

Mixed-Valence Bridged Norbornylogous Compounds as Switchable Cells for Molecular Quantum Cellular Automata: A Compromise between High Polarizability and Low Power Dissipation.

In this article, we analyze power dissipation in the nonadiabatic switching event in mixed-valence (MV) molecular cells of quantum cellular automata (QCA) in combination with a key functional property of cells such as polarizability in the applied electric field. We demonstrate that although the requirements for a strong nonlinear response of the cell to the applied electric field and low heat release are competing from the point of view of molecular parameters, this by no means can be regarded as an insurmountable obstacle for achieving functional advantages and possibility of practical application of QCA. The general theoretical consideration is applied to the series of MV compounds exemplifying electric field-switchable MV molecules, which include oxidized norbornadiene [C7H8]+ (I) and its polycyclic derivatives [C12H12]+ (II), [C17H16]+, (III), [C27H24]+ (IV), and [C32H28]+ (V). Based on the results of high-level ab initio calculations performed for the series of compounds with variable length of the bridge connecting redox groups, we show that strongly localized cation radicals with long bridges can be easily polarized even by a fairly weak electric field. This ensures quite low power dissipation, which is shown to coexist with a rather strong nonlinear cell-cell response. We thus conclude that consideration of the series of MV dimers with controllable electron transfer provides a reasonable way to design molecule-based QCA cells with the required properties.

Transition‐Metal‐Catalyzed Transformations Involving the Heck Reaction

AbstractElaborated molecular architectures including complex carbocycles, heterocycles, and polycyclic molecular structures represent an important class of organic compounds because they are ubiquitous structural units in a broad variety of biologically and pharmacologically relevant natural products, medicinal molecules, and functional materials. A major challenge in modern synthetic methodology is the development of strategically efficient and selective construction of these compounds from readily available starting materials. Transition‐metal‐catalyzed transformations involving Heck reaction as the pivotal step have afforded a powerful approach for accessing sophisticated polycyclic skeletons from a set of easy‐to handle starting materials, thus highlighting its potential significance in streamlining the drug discovery process. Over the past few decades, significant effort has been devoted to accessing complex polycyclic derivatives in efficient and versatile routes, and a number of powerful and direct synthetic strategies have been reported. In this review, the latest advances in transition‐metal‐catalyzed transformations involving Heck reaction as the critical step are summarized, which could be divided into six categories: 1) Heck/Sonogashira tandem reaction; 2) Heck/Suzuki tandem reaction; 3) Heck/Heck tandem reaction; 4) Heck/Hiyama tandem reaction; 5) Heck/Cacchi tandem reaction; 6) Heck/C−H bond functionalization tandem reaction.

Silver/chiral pyrrolidinopyridine relay catalytic cycloisomerization/(2 + 3) cycloadditions of enynamides to asymmetrically synthesize bispirocyclopentenes as PDE1B inhibitors

Significant progress has been made in asymmetric synthesis through the use of transition metal catalysts combined with Lewis bases. However, the use of a dual catalytic system involving 4-aminopyridine and transition metal has received little attention. Here we show a metal/Lewis base relay catalytic system featuring silver acetate and a modified chiral pyrrolidinopyridine (PPY). It was successfully applied in the cycloisomerization/(2 + 3) cycloaddition reaction of enynamides. Bispirocyclopentene pyrazolone products could be efficiently synthesized in a stereoselective and economical manner (up to >19:1 dr, 99.5:0.5 er). Transformations of the product could access stereodivergent diastereoisomers and densely functionalized polycyclic derivatives. Mechanistic studies illustrated the relay catalytic model and the origin of the uncommon chemoselectivity. In subsequent bioassays, the products containing a privileged drug-like scaffold exhibited isoform-selective phosphodiesterase 1 (PDE1) inhibitory activity in vitro. The optimal lead compound displayed a good therapeutic effect for ameliorating pulmonary fibrosis via inhibiting PDE1 in vivo.

Removal of hydrocarbons and heavy metals from petroleum water by modern green nanotechnology methods

Considered heavy metals, such as As(III), Bi(II), Cd(II), Cr(VI), Mn(II), Mo(II), Ni(II), Pb(II), Sb(III), Se(-II), Zn(II), and contaminating chemical compounds (monocyclic aromatic hydrocarbons such as phenolic or polycyclic derivatives) in wastewater (petrochemical industries: oil and gas production plants) are currently a major concern in environmental toxicology due to their toxic effects on aquatic and terrestrial life. In order to maintain biodiversity, hydrosphere ecosystems, and people, it is crucial to remove these heavy metals and polluting chemical compounds from the watery environment. In this study, different Nanoparticles (α-Fe2O3, CuO, and ZnO) were synthesized by green synthesis method using Portulaca oleracea leaf extract and characterized by UV–Vis spectrophotometers, FTIR spectroscopy, X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS) techniques in order to investigate morphology, composition, and crystalline structure of NPs, these were then used as adsorbent for the removal of As(III), Bi(II), Cd(II), Cr(VI), Mn(II), Mo(II), Ni(II), Pb(II), Sb(III), Se(-II), and Zn(II) from wastewater, and removal efficiencies of were obtained 100% under optimal conditions.

Synthetic Pathways to Pyrido[3,4-c]pyridazines and Their Polycyclic Derivatives

Pyrido[3,4-c]pyridazines are nitrogen-containing scaffolds that have been described as being promising in medicinal chemistry, but they are rather rare chemicals. In this review article, the literature on synthetic pathways towards pyrido[3,4-c]pyridazines is listed exhaustively, first with the bicyclic systems themselves that are obtained starting either from pyridines, pyridazines or other heterocycles. Then, the reports on the related tricyclic derivatives are discussed, again according to the source heterocycle, and finally we mention some examples on polycyclic systems.

Enantioselective, Decarboxylative (3+2)-Cycloaddition of Azomethine Ylides and Chromone-3-Carboxylic Acids.

Herein, we describe the synthesis of a variety of chiral hybrid pyrrolidine-chromanone polycyclic derivatives. A convenient (3+2)-annulation of azomethine ylides with chromone-3-carboxylic acid realized under Brønsted base catalysis produced highly functionalized products in high yields with good stereoselectivities through asymmetric, intermolecular, and decarboxylative (3+2)-cyclization.

Vibronic recovering of functionality of quantum cellular automata based on bi-dimeric square cells with violated condition of strong Coulomb repulsion.

Strong Coulomb repulsion between the two charges in a square planar mixed-valence cell in quantum cellular automata (QCA) allows us to encode the binary information in the two energetically beneficial diagonal distributions of the electronic density. In this article, we pose a question: to what extent is this condition obligatory for the design of the molecular cell? To answer this question, we examine the ability to use a square-planar cell composed of one-electron mixed valence dimers to function in QCA in a general case when the intracell Coulomb interaction U is not supposed to be extremely strong, which means that it is comparable with the characteristic electron transfer energy (violated strong U limit). Using the two-mode vibronic model treated within the semiclassical (adiabatic) and quantum-mechanical approaches, we demonstrate that strong vibronic coupling is able to create a considerable barrier between the two diagonal-type charge configurations, thus ensuring bistability and polarizability of the cells even if the Coulomb barrier is not sufficient. The cases of weak and moderate Coulomb repulsion and strong vibronic coupling are exemplified by consideration of the cation radicals of the two polycyclic derivatives of norbornadiene [C12H12]+ and [C17H16]+ with the terminal C=C chromophores playing the role of redox sites. By using the detailed ab initio data, we reveal the main characteristics of the bi-dimeric cells composed of these molecules and illustrate the pronounced effect of the vibronic recovery clearly manifesting itself in the shape of the cell-cell response function. Revealing such "vibronic recovery" of strong localization when the strong U limit is violated suggests a way to a significant expansion of the class of molecular systems suitable as QCA cells.

Controllable Electron Transfer in Mixed-Valence Bridged Norbornylogous Compounds: Ab Initio Calculation Combined with a Parametric Model and Through-Bond and Through-Space Interpretation.

In the context of a computationally guided approach to the controllable electron transfer in mixed-valence (MV) systems, in this article, we study the electron transfer (ET) in the series of oxidized norbornadiene C7H8 (I) and its polycyclic derivatives, C12H12 (II), C17H16, (III), C27H24 (IV), and C32H28 (V), with variable lengths of the bridge connecting redox sites. The work combines an ab initio CASSCF evaluation of the electronic structure of systems I-V with the parametric description in the framework of the biorbital two-mode vibronic model. The model involves coupling with the "breathing" mode and intercenter vibration modulating the distances between the redox fragments. The ab initio calculations were performed for two types of optimized structures of I-V: (a) charge-localized global minimum (Cs) and (b) symmetric configuration (C2v) with the delocalized charge. This allows one to estimate the potential barrier separating charge-localized configurations as well as vibronic coupling parameters and the electron transfer integral. Along with the adiabatic approach, the quantum-mechanical analysis of the vibronic levels has been applied to precisely estimate the quantum effect of tunneling splitting. We estimate the "through-space" and "through-bond" contributions to the parameters interrelated with the charge transfer (CT). The through-space effect proves to be a major factor of ET at a short distance between the redox centers, whereas the through-bond contribution is dominant at a long distance. Vibronic coupling under the condition of through-space ET leads to the localization of the positive charge on the π-chromophore, while the through-bond component of ET results in compensating σ-shifts and subsequent charge delocalization over the bridge. The limitations of the parametric approach were discussed in the context of the two components contributing to the ET. Particularly, the bridge polarization in the course of through-bond ET proves to be beyond the basis of the employed parametric model.

Diene-transmissive hetero-Diels–Alder reaction of distyryl thioketone

The reaction distyryl thioketone with donor alkenes (norbornene and styrene) gives adducts of the hetero-Diels–Alder reaction. In the case of maleic acid derivatives, a tandem reaction occurs which leads to polycyclic derivatives of 3,4-dihydro-2H-thiopyran. The stereochemical features of the ongoing transformations were examined.

Application of QuEChERS with GC/MS/MS for monitoring polycyclic aromatic hydrocarbon (PAHs) contaminants in Turkish flora honey produced in urban and rural areas

ABSTRACT Environmental pollution has been a problem waiting for solutions worldwide in recent years. Pollution with polycyclic aromatic hydrocarbon (PAHs), oil, and petroleum derivatives, may have long- and short-term environmental and health effects. Bee products are used as bioindicators to determine environmental pollution. In this work, 16 PAHs compounds were analyzed in honey samples from different Turkey regions by gas chromatography-tandem mass spectrometry (GC/MS/MS). In this work, the modern extraction method (QuEChERS) was selective and sensitive enough to extract 16 PAHs from honey samples. High amounts of naphthalene (22.5 µg kg−1), acenaphthylene (16.2 µg kg−1), acenaphthene (17.3 µg kg−1), fluorene (13.3 µg kg−1), phenanthrene (14.5 µg kg−1), fluoranthene (11.9 µg kg−1), benzo(b)fluoranthene (12.6 µg kg−1), benzo(k)fluoranthene (12.7 µg kg−1), and benzo(a)pyrene (11.7 µg kg−1) were detected. Besides, PAHs levels in the Marmara region were very high. The differences in PAHs content between honey from rural and urban areas could be related to atmospheric conditions such as exhaust gases, dust, and airborne particles or from soils in which the plants grow.

Berberine bridge enzyme-like oxidase-catalysed double bond isomerization acts as the pathway switch in cytochalasin synthesis

Cytochalasans (CYTs), as well as their polycyclic (pcCYTs) and polymerized (meCYTs) derivatives, constitute one of the largest families of fungal polyketide-nonribosomal peptide (PK-NRP) hybrid natural products. However, the mechanism of chemical conversion from mono-CYTs (moCYTs) to both pcCYTs and meCYTs remains unknown. Here, we show the first successful example of the reconstitution of the CYT core backbone as well as the whole pathway in a heterologous host. Importantly, we also describe the berberine bridge enzyme (BBE)-like oxidase AspoA, which uses Glu538 as a general acid biocatalyst to catalyse an unusual protonation-driven double bond isomerization reaction and acts as a switch to alter the native (for moCYTs) and nonenzymatic (for pcCYTs and meCYTs) pathways to synthesize aspochalasin family compounds. Our results present an unprecedented function of BBE-like enzymes and highly suggest that the isolated pcCYTs and meCYTs are most likely artificially derived products.