N-containing Heterocycles Research Articles

Compilation of the Antimicrobial Compounds Produced by Burkholderia Sensu Stricto.

Due to the increase in multidrug-resistant microorganisms, the investigation of novel or more efficient antimicrobial compounds is essential. The World Health Organization issued a list of priority multidrug-resistant bacteria whose eradication will require new antibiotics. Among them, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae are in the "critical" (most urgent) category. As a result, major investigations are ongoing worldwide to discover new antimicrobial compounds. Burkholderia, specifically Burkholderia sensu stricto, is recognized as an antimicrobial-producing group of species. Highly dissimilar compounds are among the molecules produced by this genus, such as those that are unique to a particular strain (like compound CF66I produced by Burkholderia cepacia CF-66) or antimicrobials found in a number of species, e.g., phenazines or ornibactins. The compounds produced by Burkholderia include N-containing heterocycles, volatile organic compounds, polyenes, polyynes, siderophores, macrolides, bacteriocins, quinolones, and other not classified antimicrobials. Some of them might be candidates not only for antimicrobials for both bacteria and fungi, but also as anticancer or antitumor agents. Therefore, in this review, the wide range of antimicrobial compounds produced by Burkholderia is explored, focusing especially on those compounds that were tested in vitro for antimicrobial activity. In addition, information was gathered regarding novel compounds discovered by genome-guided approaches.

Overview of 1,5-Selective Click Reaction of Azides with Alkynes or Their Synthetic Equivalents.

Nowadays, the click reaction of azides with alkynes has evolved rapidly and become one of the most efficient methods to synthesize 1,2,3-triazoles, which are an important class of N-containing heterocycles. While the 1,4-selective click reaction of azides with alkynes is well established to synthesize 1,4-substituted 1,2,3-triazoles, the corresponding 1,5-selective click reaction for the generation of 1,5-substituted-1,2,3-triazoles is much less explored, and there is no systematic review for the 1,5-selective click reaction. This timely review summarizes the discovery and development of 1,5-selective click reactions of azides with alkynes for the synthesis of 1,5-substituted 1,2,3-triazoles. The 1,5-selective click reactions will be divided into three types according to the critical reactive intermediates: metallacyclic intermediates, acetylide intermediate, and formal 1,5-selective azide-alkyne cycloaddition. The related mechanistic studies will also be involved in this review.

A green hybrid extraction process for thiophene, quinoline and indole recovery from light hydrocarbon fractions

"Green" extraction technologies are fundamental to many processing plants in order to improve the deteriorating environmental situation in the world. This work presents a combination of two "green" extraction technologies: liquid extraction based on water-soluble polymers, as an environmentally attractive method for the isolation, separation and concentration of substances, and supercritical fluid extraction, as an environmentally safe method for the isolation of valuable components from aqueous polymer solutions. Polyvinylpyrrolydone 3500 (PVP-3500) has demonstrated high extraction ability for quinoline and indole with one-step extraction efficiency up to 82% and 94% respectively from solutions simulating light hydrocarbon fractions. Concomitant versatile research allowed building the dependences between quantitative quinoline and indole extraction characteristics and such process parameters as: the phases contact time, the extraction system composition, the initial concentration of nitrogen-containing compounds in n-hexane, the volume fraction of the extractant and the process temperature in the heterogeneous system PVP-3500 – n-hexane – water. It was found that PVP-3500 possesses weak extraction affinity for sulfur-containing compounds, which makes it promising for use in the separation of S- and N-containing heterocyclic compounds. In addition, we propose a new environmentally friendly approach for the purification of polymers used in the study based on the countercurrent extraction with supercritical carbon dioxide. Particularly, using the latter method instead of static supercritical purification mode leads to significant increase in quinoline and indole extraction efficiency from an aqueous solution of PVP-3500.

Room temperature continuous flow synthesis of γ-valerolactone and N-containing heterocycles over Ru supported bimodal N,S-doped cubic mesoporous carbon

One of the key steps in producing value-added chemicals from biomass-derived compounds is the conversion of levulinic acid (LA) into γ-valerolactone and related N-containing heterocycles.

Sulfonamides with Heterocyclic Periphery as Antiviral Agents.

Sulfonamides are the basic motifs for a whole generation of drugs from a large group of antibiotics. Currently, research in the field of the new sulfonamide synthesis has received a "second wind", due to the increase in the synthetic capabilities of organic chemistry and the study of their medical and biological properties of a wide spectrum of biological activity. New reagents and new reactions make it possible to significantly increase the number of compounds with a sulfonamide fragment in combination with other important pharmacophore groups, such as, for example, a wide class of N-containing heterocycles. The result of these synthetic possibilities is the extension of the activity spectrum-along with antibacterial activity, many of them exhibit other types of biological activity. Antiviral activity is also observed in a wide range of sulfonamide derivatives. This review provides examples of the synthesis of sulfonamide compounds with antiviral properties that can be used to develop drugs against coxsackievirus B, enteroviruses, encephalomyocarditis viruses, adenoviruses, human parainfluenza viruses, Ebola virus, Marburg virus, SARS-CoV-2, HIV and others. Since over the past three years, viral infections have become a special problem for public health throughout the world, the development of new broad-spectrum antiviral drugs is an extremely important task for synthetic organic and medicinal chemistry. Sulfonamides can be both sources of nitrogen for building a nitrogen-containing heterocyclic core and the side chain substituents of a biologically active substance. The formation of the sulfonamide group is often achieved by the reaction of the N-nucleophilic center in the substrate molecule with the corresponding sulfonylchloride. Another approach involves the use of sulfonamides as the reagents for building a nitrogen-containing framework.

Ultrasound-assisted multicomponent synthesis of pyrido[2,3-d]pyrimidine derivatives and their DFT calculations: A green approach

Pyrido[2,3-d]pyrimidines with their diverse biological potential became a highly significant class of N-containing heterocyclic compounds. They are prepared by the reaction of cinnamaldehyde and aminopyrimidine with 1,3-diketones (hydroxynaphthaquinone and hydroxycoumarin) by applying a knoevenagel condensation followed by a Michael addition multicomponent procedure. Although a few methods have been developed for synthesizing these compounds, they have advantages and disadvantages. Hence, developing a simple, efficient, and environmentally benign methodology for preparing these molecules in the presence of green reaction conditions is still in great demand. Therefore, this article describes an ultrasound-mediated multicomponent protocol to produce pyrido[2,3-d]pyrimidine under neat conditions. Further geometric optimizations, a frontier molecular orbital approach, and the molecular electrostatic potential for the synthesised chemical 4c and 5a were carried out using a computer density functional investigation. The DFT investigation was conducted using the B3LYP/6-311G (d,P) level of theory as the basis set.

A Review on The Medicinal And Industrial Applications of N-Containing Heterocycles

Nitrogen-containing heterocycles constitute an important division of organic chemistry. The structural and functional diversity in nitrogen-containing heterocyclic compounds emanates from the presence and nature of the heteroatom that optimizes the compound for a specific application. Nitrogen heterocycles have been found to mimic various endogenous metabolites and natural products, highlighting their pivotal role in current drug design. Their applications are manifold and are predominantly used as pharmaceuticals, corrosion inhibitors, polymers, agrochemicals, dyes, developers,etc. Additionally, their catalytic behavior has rendered these compounds notable precursors in synthesizing various important organic compounds. The rate at which nitrogen heterocycles are synthesized explains this organic chemistry domain's vitality and usefulness. The present review article focuses on nitrogen-containing heterocycles as a versatile scaffold for current applications of organic chemistry.

Catalytic gasification of indole in supercritical water with non-noble bimetallic catalysts

Indole is commonly reported as a N-containing heterocyclic compounds in biomass supercritical water gasification (SCWG), and is difficult to be degraded to small molecule substances. In this work, Ni/AC, Ni–Cu/AC, Ni–Co/AC, Ni–Ce/AC were prepared and tested for catalytic SCWG of indole. The results showed that Ni–Cu/AC had the highest activity for converting indole and producing gases, leading to the highest hydrogen gasification efficiency (135.1%) and carbon gasification efficiency (33.1%). During the catalytic SCWG of indole, the addition of auxiliary metal Cu in multi-component catalyst showed synergistic effects by changing reaction pathways and reaction rates. It significantly promoted water-gas shift and steam reforming reactions, so forming the highest H2 yield of 2.62 mol mol−1. Furthermore, large specific surface, Ni reduction and high catalyst stability point to potential advantages of the Ni–Cu/AC catalyst for catalytic SCWG of recalcitrant N-containing compounds.

Synthesis, In Silico, and In Vitro Biological Evaluation of New Furan Hybrid Molecules

Herein, we report the synthesis of new hybrid molecules between furan and N-containing heterocyclic compounds such as pyrrolidine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, and piperidine. The obtained compounds were fully characterized using 1H- and 13C-NMR, UV-Vis, and HRMS spectra. All compounds were assessed for their anti-inflammatory, anti-arthritic, antioxidant, reducing power ability, and chelating activity. The less lipophilic molecules H2 (60.1 ± 8.16) and H4 (62.23 ± 0.83) had almost 12 times higher ATA compared with the used ketoprofen (720.57 ± 19.78) standard. The inhibition of albumin denaturation results makes the newly obtained hybrids potential anti-inflammatory drugs, as the expressed values are higher than the ketoprofen standard (126.58 ± 5.00), except H3 (150.99 ± 1.16). All four compounds show significant activity regarding the in vitro biological activities, which makes them great candidates for potential future drugs.

Synthesis and characterization of asymmetric oxyacetamide bridged porphyrin conjugates embedded with N-containing heterocycles

In the search for photosensitizers based on 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (m-THPP, 1), a novel series of asymmetric A3B porphyrin molecules with oxyacetamide linkers have been synthesized. A facile synthetic route was followed through the reaction of m-THPP derived porphyrin monoacid with amino-heterocyclic molecules in the presence of HBTU/DIPEA coupling reagent to obtain the respective porphyrin conjugates 7-10, 16, 18 in satisfactory yields 30–76%. The structures of all compounds were confirmed by the means of 1H, [Formula: see text]C NMR and by mass spectrometry (MALDI-TOF). The absorption and emission spectra of the synthesized porphyrin conjugates were displayed in methanol and showed high extension coefficient values. These preliminary studies could qualify these new candidates in being added to the porphyrin library for photomedicine applications.

Enantioselective Nickel-Catalyzed C(sp3 )-H Activation of Formamides.

Enantioselective Ni-catalyzed C(sp3 )-H bond activation remains an elusive challenge. Herein, we used phosphine oxide-ligated Ni-Al bimetallic catalyst to realize enantioselective Ni-catalyzed aliphatic C(sp3 )-H activation of formamides, providing a series of chiral N-containing heterocycles in 40-95 % yield and 70-95 % ee.

A Three-Component Approach to (Hetero)arenes with Two N-Containing Heterocycle Motifs

AbstractA one-pot, three-component reaction involving SNAr-decarboxylative redox isomerization starting from an electron-withdrawing group bearing fluorobenzaldehyde or fluorothiophenecarbaldehyde (electron-pair diacceptor), secondary amine, and trans-4-hydroxy-l-proline or indoline-2-carboxylic acid (electron-pair donor) has been developed to give N-[(pyrrolylmethyl)-substituted (het)aryl]- and N-[(indolyl­methyl)-substituted (het)aryl]pyrrolidines, -piperidines, -morpholines, and -azocanes. The highlights of this protocol are its great convenience in the simultaneous construction of a C(sp2)–N bond and a C(sp3)–N bond with simple operation; the reaction can be performed on a gram scale. This efficient one-pot multicomponent reaction has potential as a novel method for drug synthesis, especially involving polycyclic compounds.

Biofuel potential of liquid products from protein- and lipid-rich biomass hydrothermal liquefaction

Hydrothermal liquefaction (HTL) of oleaginous microorganisms is an economical method with which to transform all compounds of wet biomass into competitive biofuels without the need for pretreatments such as feedstock drying and lipid extraction. In the present work, liquefaction of microalgae or yeasts in subcritical water is investigated in a self-built HTL system. Fractional yield distribution of the end-products and characterization of biocrudes from algae HTL are studied by considering the effects of the reaction temperature and residence time. The identified compounds in the biocrudes are compared to those in yeast-derived HTL biocrudes and the reaction scheme is reported. The present work reveals that no significant quality change of algae-derived HTL biocrudes is observed in a moderate temperature range thus the N-containing compounds vary complicatedly at different residence times. Compared to the pyrolysis biocrudes of algae and yeast, the collected HTL biocrudes do not perform the advantage, in terms of biofuel potential of a high portion of N-containing compounds, especially heterocyclic compounds. It should be noted that the low protein content in the feedstocks cannot definitely be proven to have led to the reduced heterocyclic compounds in HTL biocrudes. If lipids had been present, this would have enhanced the formation of N-containing heterocyclic compounds. Instead, amino acid degradation was accelerated by the high level of carbohydrates, forming amides. This paper presents a promising effort to develop an efficient route to transform oleaginous microorganisms into biofuels.

Reaction of Chlorine Dioxide with Saturated Nitrogen-Containing Heterocycles and Comparison with the Micropollutant Behavior in a Real Water Matrix.

Chlorine dioxide (ClO2) is a very selective oxidant that reacts with electron-rich moieties such as activated amines and thus can degrade specific N-containing micropollutants. N-containing heterocycles (NCHs) are among the most frequent moieties of pharmaceuticals. In this study, the reactions of ClO2 with ritalinic acid and cetirizine, two abundant micropollutants, and model compounds representing their NCH moiety were investigated. The pH-dependent apparent reaction rates of all NCHs with ClO2 were measured and modeled. This model showed that neutral amines are the most important species having reaction rates between 800 and 3200 M-1 s-1, while cationic amines are not reactive. Ritalinic acid, cetirizine, and their representative model compounds showed a high stoichiometric ratio of ≈5 moles ClO2 consumption per degraded ritalinic acid and ≈4 moles ClO2 consumption per degraded cetirizine, respectively. Investigation of chlorine-containing byproducts of ClO2 showed that all investigated NCHs mostly react by electron transfer and form above 80% chlorite. The reactions of the model compounds were well comparable with cetirizine and ritalinic acid, indicating that the model compounds indeed represented the reaction centers of cetirizine and ritalinic acid. Using the calculated apparent reaction rate constants, micropollutant degradation during ClO2 treatment of surface water was predicted for ritalinic acid and cetirizine with -8 to -15% and 13 to -22% error, respectively. The results indicate that in ClO2-based treatment, piperidine-containing micropollutants such as ritalinic acid can be considered not degradable, while piperazine-containing compounds such as cetirizine can be moderately degraded. This shows that NCH model compounds could be used to predict micropollutant degradation.

Transition-metal-free synthesis of pyrimidines from lignin β-O-4 segments via a one-pot multi-component reaction

Heteroatom-participated lignin depolymerization for heterocyclic aromatic compounds production is of great importance to expanding the product portfolio and meeting value-added biorefinery demand, but it is also particularly challenging. In this work, the synthesis of pyrimidines from lignin β-O-4 model compounds, the most abundant segment in lignin, mediated by NaOH through a one-pot multi-component cascade reaction is reported. Mechanism study suggests that the transformation starts by NaOH-induced deprotonation of Cα-H bond in β-O-4 model compounds, and involves highly coupled sequential cleavage of C-O bonds, alcohol dehydrogenation, aldol condensation, and dehydrogenative aromatization. This strategy features transition-metal free catalysis, a sustainable universal approach, no need of external oxidant/reductant, and an efficient one-pot process, thus providing an unprecedented opportunity for N-containing aromatic heterocyclic compounds synthesis from biorenewable feedstock. With this protocol, an important marine alkaloid meridianin derivative can be synthesized, emphasizing the application feasibility in pharmaceutical synthesis.

Discovery of 1,3,4-oxadiazole derivatives containing a bisamide moiety as a novel class of potential cardioprotective agents

Myocardial injury is a nonnegligible problem in cardiovascular diseases and cancer therapy. The functional feature of N-containing heterocycles in the cardiovascular field has attracted much attention in recent years. Herein, we discovered a lead compound 12a containing 1,3,4-oxadiazole by extensive screening of anticancer derivatives containing nitrogen-heterocycle, which exhibited potential protective activity against oxidative stress in cardiomyocytes. Follow-up structure-activity relationship (SAR) studies also highlighted the role of substitution sites and bisamide moiety in enhancing the protective activity against oxidative stress. Specifically, compound 12d exhibited low cytotoxicity under high concentration and potent myocardial protection against oxidative stress in H9c2 cells. Preliminary mechanistic studies showed compound 12d could decrease the expression of cardiac hypertrophy and oxidative stress-related proteins/genes and reduce mitochondria-mediated cell apoptosis, thereby enhancing the cell vitality of injured cardiomyocytes. In this study, 1,3,4-oxadiazole may represent a novel pharmacophore that possesses potential myocardial protection and provides more choices for future optimization of cardiovascular drugs, especially for the treatment of onco-cardiology.

Synthesis, crystal structure and photocatalytic properties of two bismuth(III) complexes with different N-containing heterocycles

Two novel bismuth(III) complexes of the formulae (2-HMI)4[Bi2Cl10] (1) and {(Hphen)[BiCl4]}n (2) (2-MI = 2-methylimidazole, Hphen = 1,10-phenanthroline) were synthesized. The complexes were characterized by elemental analyses, X-ray diffraction, Fourier transform infrared spectra and thermogravimetry analysis. The X-ray crystallographic investigation reveals that 1 is ionic compound built of 2-methylimidazolium cations and binuclear metalate anions, [Bi2Cl10]4–. 2 is a coordination polymer, and its asymmetric structural units are connected by one Bi3+ ion, four Cl– ions and one disordered and protonized Hphen+ cation. In addition, the photocatalytic activities of 1 and 2 towards the degradations of Rhodamine B (RhB) and methylene blue (MB) were explored, and the mechanism of the photocatalytic degradation was also discussed. The results show that 1 and 2 are good candidates for photocatalytic degradation of RhB and 2 is also a good candidate for photocatalytic degradation of MB.

Effects of demineralization and devolatilization on fast pyrolysis behaviors and product characteristics of penicillin mycelial residues

In this study, the effects of demineralization and devolatilization methods including of water washing (WW), torrefaction (TF), washing-torrefaction (WT) and hydrothermal treatment (HT) on the fast pyrolysis characteristics of penicillin mycelial residues were studied. The materials and pyrolysis products were characterized by analysis methods including of thermogravimetric (TG), gas chromatograph (GC), gas chromatography-mass spectrometry (GC-MS), x-ray diffractometer (XRD), fourier transform-infrared spectroscopy (FT-IR) and x-ray photoelectron spectroscopy (XPS), etc. The results showed WW increased the yields of tar and decreased the yields of pyrolysis biochar due to the removal of alkali and alkaline earth metals (AAEMs), while TF and HT showed opposite results due the devolatilization. XPS and FT-IR results proved that the conversion from aliphatic C-(C, H) to aromatic groups C-O-C and CO was the key point for improving the aromatization of biochar. Pretreatments increased the relative proportions of N-containing heterocyclic compounds and phenolic compounds, reduced the proportions of O-containing heterocyclic compounds in pyrolysis tar. And TF and HT could eliminate the residual antibiotic and satisfy the principle of AMR harmless disposal.

Photoredox synthesis of 6- and 7-membered ring scaffolds via N-centered radicals.

N-Containing heterocycles are important scaffolds due to their ubiquitous presence in bioactive compounds. Their synthesis has been considered as an important research field. In this work we report the access to 6- and 7-membered rings via a photoinduced strategy. To our knowledge, this work represents the first exemple of photo-induced 7-endo-trig cyclization with N-centered radicals.

Nanocatalysts: applications for the synthesis of N-containing five-membered heterocycles.

Using transition metals as nanocatalysts has opened up a vast new area in heterocyclic chemistry in the modern day. Heterocyclic moieties are significant scaffolds that have both pharmacological and industrial applications. Various scientific groups have focused their attention on the expansion of simple reaction protocols by introducing better functional group compatibilities under mild reaction conditions through the use of easily available starting materials. This review provides an outline of the applications of metallic nanoparticles as proficient, recyclable, low-cost and green heterogeneous catalysts for the preparation of a wide range of key therapeutic five-membered nitrogen-containing heterocyclic compounds as well as some other significant functionalizations over the rings. This review mainly covers the literature published through the period from 2004 to 2021.