Quinolinone Derivatives Research Articles

Iodine‐Mediated Oxidative C=C Double‐Bond Formation toward Fused Quinolinones and Quinolinium Salts

An iodine‐mediated C=C double bond‐forming reaction has been established to access various fused quinolinone derivatives under transition metal‐free conditions. The present reaction is also applicable to the synthesis of fused quinolinium frameworks from the corresponding precursors and can be conducted on a gram scale.

One-pot three-component synthesis of 2,4-dimethoxy-5,8,9,10-tetrahydropyrimido[4,5-b]quinolinone derivatives along with in silico and in vitro investigation of their antimalarial activity

Pyrimidoquinolinone-derived compounds have exhibited a broad spectrum of biological activities and have been acknowledged as a potential antimalarial scaffold through multiple conventional strategies. In the present study, a novel series of 2,4-dimethoxy-5,8,9,10-tetrahydropyrimido[4,5-b]quinolinones 4(a-m) were synthesized via a one-pot three-component reaction of cyclohexane-1,3‑dione, 4-amino-2,6-dimethoxypyrimidine and various aldehyde with l-proline as the catalyst and acetic acid as the solvent under reflux condition. In vitro antimalarial activity toward P. falciparum 3D7 strain cultures were investigated. Compounds 4b and 4m demonstrated significant efficacy against strains of P. falciparum, with IC50 values of 0.63 and 0.65 μg/mL, respectively. The results were also supported by molecular docking and ADME assays.

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.

Harnessing the Photoperformance of N-Methyl-Quinolinone for Gated Photo-Driven Cyclability and Reversible Photoligation.

[2π + 2π]-photocycloadditions and their ability to trigger controlled and reversible photoligation through disparate wavelengths provide an attractive platform to unlock advanced functionalities in soft materials. Yet, among the limited amount of functional motifs enabling reversible photoreactions, cyclability is often overlooked due to poor reaction yield and orthogonality. In this study, the advantageous photocharacteristics of the previously underexplored N-methyl-quinolinone photoresponsive motif are leveraged to create a covalent gated system, enabling controlled formation and cleavage of covalent bonds on demand. A systematic evaluation of individual cycloadditions and reversions on the molecular scale, including reaction rates, conversions, and photoproducts, allows identification of the required conditions for generating controlled photoreactions with a remarkable degree of cyclability; while, maintaining high reaction yields. Ultimately, these controlled and cyclable reactions are translated to a macromolecular scale, showcasing a comparable performance in initiating reversible photoligation, as observed at the molecular level. In addition, it is also shown that this progressive methodology can be leveraged to gain a comprehensive understanding of cyclability and clarify the factors contributing to its decreasing yield. Overall, unlocking the potential of quinolinone derivatives through this step-by-step approach lays the foundation for the development of highly controlled and responsive polymer materials with unprecedented potential.

Design, Synthesis, and Biological Evaluation of Quinoline (Quinolinone) Derivatives as NADPH Oxidase (NOX) Inhibitors.

NADPH oxidases (NOXs) are the sole enzyme in the human body that can directly produce reactive oxygen species. Recent studies have shown that NOXs is a very promising target for the treatment of diabetic nephropathy (DN). Here, a series of quinoline(quinolinone) derivatives have been designed based on pharmacophore strategy, synthesized and evaluated. Among them, 19d exhibits potent antiproliferative and NOXs inhibitory activities, and is worthy for further investigation.

Catalytic asymmetric desymmetrization of 1,4-cyclohexadienes for the synthesis of chiral quinolinone derivatives

Quinolinone is a prevalent nitrogen-containing heterocycle in organic and pharmaceutical chemistry. In this report, we developed an intramolecular catalytic asymmetric Heck reaction of symmetrical 1,4-cyclohexadiene to construct quinolinone derivatives. The Pd(OAc)2/(R)-BINAP catalytic system enabled a series of quinolinone analogs containing two consecutive chiral centers to be obtained with up to 76% yield and 95% ee. Meanwhile, the synthesis of quinolinones bearing an all-carbon quaternary center and three consecutive chiral centers was also achieved in 85% ee via PdCl2/(R)-BoPhoz catalyzed intramolecular asymmetric Heck/alkylation reaction.

Intramolecular Palladium(II)-Catalyzed Regioselective 6-endo or 6-exo C-H Benzannulation: An Approach for the Diversity-Oriented Synthesis of Quinolinone Derivatives from Pyridones.

Herein, a new intramolecular palladium(II)-catalyzed regioselective 6-endo-trig or 6-exo-trig annulation through direct C-H activation is presented as a method for the diversity-oriented synthesis of highly substituted quinolinones from pyridones. The reaction occurs under mild conditions and exhibits excellent regioselectivity, good functional group tolerance, and broad applications. This innovative approach has been successfully utilized in the synthesis of Glycopentanolone A and an intermediate of (R)-(+)-Tipifarnib.

Design, synthesis and activity evaluation of quinolinone derivatives as EZH2 inhibitors

The enhancer of zeste homologue 2 (EZH2) is the core catalytic subunit of polycomb repressive complex 2, which catalyzes lysine 27 methylation of histone H3.Herein, a series of quinolinone derivatives were designed and synthesized based on the structure of Tazemetostat as the lead compound. Compound 9l (EZH2WT IC50 = 0.94 nM) showed stronger antiproliferative activity in HeLa cells than the lead compound. Moreover, compound 9e (EZH2WT IC50 = 1.01 nM) significantly inhibited the proliferation and induced apoptosis in A549 cells.

Regioselective synthesis of N-containing polycyclic compounds via radical annulation cyclization of 1,7-dienes with aldehydes.

A convenient method for oxidant-promoted radical cascade acylation or decarbonylative alkylation of 1,7-dienes with aldehydes has been established. This method allows for the rapid construction of N-containing polycyclic skeletons in a highly regio- and stereoselective manner. This transformation provides a simple and efficient method for the preparation of a range of tetrahydro-6H-indeno[2,1-c]quinolinone derivatives by sequential formation of three new carbon-carbon bonds. Additionally, this radical cascade cyclization can selectively convert aldehydes into aroyl/primary aliphatic acyl radicals and secondary or tertiary alkyl radicals.

Light-induced isomerization of quinoline-N-oxide derivatives through Zn-catalysis: a photochemical approach for synthesizing 2-quinolinone derivatives

The light-induced Zn-catalyzed isomerization of quinoline-N-oxides proceeded smoothly to afford 2-quinolinone derivatives via intramolecular hydrogen and oxygen transfer.

Copper-catalyzed desymmetric silylative-cyclization of 1,6-diynes for synthesis of spirocyclic compounds

The silylative-cyclization desymmetrization of 1,6-diynes has been realized. This reaction enabled the construction of silyl-functionalized spirocyclic oxindoles, indanone, quinolinone, and tetralone derivatives from readily available 1,6-diynes.

MCM‐41@CPTMS as an Efficient and High‐Performance Catalyst for One‐Pot Construction of Indeno[1,2‐b]quinolin‐8‐one Derivatives**

AbstractIn this work, MCM‐41@CPTMS nanoparticles were readily prepared and evaluated as acidic nanosilica spheres for the synthesis of indeno[1,2‐b]quinolinone derivatives through one‐pot three‐component reaction of 1‐naphthylamine, aromatic aldehydes and 1,3‐indandione. A high surface area, a hexagonal array of uniform mesoporous, high thermal stability, recyclability, nontoxicity and the easy separation of the nanocatalyst, make this nanocatalyst very useful for the synthesis of organic compounds. Mesoporous silica nanoparticles (MSN) was prepared easily and affirmed to be effective and prepared the products with excellent yields under reflux conditions. The structure of obtained nanoparticles was characterized by FE‐SEM, TEM, EDX, FT‐IR, XRD, TGA and BET. This synthetic protocol provides several benefits such as excellent yields in short reaction times (83–97 %),saving costs, reusability of the catalyst (five runs), and low catalyst loading.

Synthesis of novel pyrazolyl quinolinone derivatives and their physicochemical applications on polyester

Graphical abstract Purpose This study aims to synthesize new disperse dyes based on novel pyrazolyl quinolinone derivatives EQ1 and EQ2 and evaluate their characteristics after dyeing them on a polyester fabric. Design/methodology/approach New dispersed dyes based on pyrazolyl quinolinone derivatives were prepared and confirmed by different analyses, such as infrared spectroscopy, elemental microanalysis and nuclear magnetic resonance spectroscopy. They were dyed on a polyester fabric. The characteristics of dyed polyester were determined by color measurements such as a*, b*, L*, C*, E, Ho, R% and color strength. The electronic structures of EQ1 and EQ2 in gaseous state were investigated using density functional theory/B3LYP/6-311++G (d, p) level of theory. Findings The suitability of the prepared dyestuffs for dyeing on polyester fabrics has been investigated. The study was concerned with comparing the contrasting depth of shade and levelness. The study was concerned mainly with dye uptake and color measurements at two different temperatures. The results showed that the exhaustion values of dyes inside the polyester at 130°C were higher than those obtained at conventional dyeing temperature (100°C). The exhaustion values of EQ2 were greater than those of EQ1 at 130°C with 2.2%, while the brightness of EQ2 was higher than that of EQ1 at the two investigated temperatures. The results of molecular orbital calculations show that the studied compounds are planar. In addition, the ionization potential of EQ1 was lower than that of EQ2. The results of the theoretical study helped in understanding the dyeing behavior of the investigated azo dyes. Originality/value The prepared disperse dyes based on pyrazolyl quinolinone derivatives could be used in textile dyeing of polyester on an industrial scale.

Palladium‐Catalyzed Carbonylation of Multifunctionalized Substituted Alkynes to Quinolinone Derivatives under Mild Conditions†

Comprehensive SummaryA highly selective palladium‐catalyzed carbonylation of 2‐alkynylanilines bearing an amide moiety to condensed six‐membered heterocyclic structures has been developed under mild conditions (room temperature and atmospheric pressure of CO). The carbonylative protocol is also compatible with CO surrogates, such as benzene‐1,3,5‐triyl triformate (TFBen) or the newly developed calix[6]arenes functionalized with six formate groups (CLX[6]CO), which are both capable to release CO in situ. A series of tricyclic fused heterocycles containing the important oxazino‐quinolinone scaffold have been selectively obtained (only the 6‐endo‐dig cyclization mode has been observed) in good to excellent yields (up to 99%).

Oxepine-containing pyrazinopyrimidine alkaloids and quinolinone derivatives produced by Aspergillus versicolor AS-212, a deep-sea-derived endozoic fungus

Four new oxepine-containing pyrazinopyrimidine alkaloids, versicoxepines A − D (1–4), two quinolinone alkaloid analogs including 3-hydroxy-6-methoxy-4-phenylquinolin-2(1H)-one (5) and 3-methoxy-6-hydroxy-4-phenylquinolin-2(1H)-one (6) which were new naturally occurring compounds, together with two known compounds (7 and 8) were isolated from Aspergillus versicolor AS-212, an endozoic fungus isolated from the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts in the Western Pacific Ocean. Their structures were determined by extensive analysis of the spectroscopic and X-ray crystallographic data as well as by chiral HPLC analysis, ECD calculation, and DP4+ probability prediction. Structurally, versicoxepines B and C (2 and 3) represent the first example of a new oxepine-containing pyrazinopyrimidine alkaloid whose cyclic dipeptide moiety is composed of the same type of amino acid (Val or Ile). Compound 5 displayed antibacterial activity against aquatic pathogens, Vibrio harveyi and V. alginolyticus, with MICs of 8 μg/mL.

Chemoselective Condensation of 3-Amino-2-cyclohexenones with Cinnamaldehydes: Switchable Synthesis of Dihydroquinolinones and Hexahydroacridinediones.

Herein, a chemoselective condensation of 3-amino-2-cyclohexenones and cinnamaldehydes for switchable synthesis of dihydroquinolinones and hexahydroacridinediones was developed. Mechanism analysis showed that the formation of dihydroquinolinones involved trimolecular condensation and oxidative aromatization, while the formation of hexahydroacridinediones involved acid hydrolysis of enaminone and dehydration-aromatization. This strategy provides a convenient way to switch from the same substrates to produce two different quinolinone derivatives.

Visible-Light-Active Coumarin- and Quinolinone-Based Photocatalysts and Their Applications in Chemical Transformations.

Organic dyes have been actively studied as useful photocatalysts because they allow access to versatile structural flexibility and green synthetic applications. The identification of a new class of robust organic chromophores is, therefore, in high demand to increase structural diversity and variability. Although coumarins and quinolinones have long been acknowledged as organic chromophores, their ability to participate in photoinduced transformations is somewhat less familiar. Fascinated by their chromophoric features and adaptable platform, our group is interested in the identification of fluorescent bioactive molecules and in the development of new photoinduced synthetic methods using coumarins and quinolinones as photocatalysts. This account provides an overview of our recent progress in the discovery and application of light-absorbing coumarin and quinolinone derivatives in photochemistry and medicinal chemistry.

Microwave assisted one-pot access to pyrazolo quinolinone and tetrahydroisoxazolo quinolinone derivatives via T3P®-DMSO catalysed tandem oxidative-condensation reaction.

A new approach for the synthesis of two important annulated pyrazolo quinolinone and tetrahydroisoxazolo quinolinone derivatives from multicomponent reactions was achieved by using T3P®-DMSO-catalysed reactions of stable alcohols, cyclic 1,3-dicarbonyl compounds and amino derivatives of phenyl pyrazoles and isoxazole and has been reported for the first time. This reaction occurred via a tandem oxidative-condensation reaction under microwave irradiation and notable characteristics of this protocol are MCR reactions, shorter reaction time, less waste creation, ease of workup, stable precursors, broad substrate scope and functional group tolerance.

Regio- and stereoselectivity of the 1,3-dipolar cycloaddition of azomethine ylides to 3-nitro-2(1H)-quinolinone derivatives: A new synthesis of Pyrrolo[3,4-c] quinolines

1,3-Dipolar cycloadditions of different azomethine ylides to 3-nitro-2(1H)-quinolinones were carried out to give 3a-nitro-4-oxo-1,2,3,3a,5,9b-hexahydropyrrolo[3,4-c]quinoline-4-one derivatives in satisfactory yield, in most cases with excellent stereoselectivity. The structure and stereochemistry of cycloadducts were studied in detail by X-ray and NMR spectroscopy methods.

Temperature Tunable Synthesis of Tetrahydro-4H-pyrrolo[3,2-c]quinolin-4-ones and Dihydro-1H-benzo[b]azepines from 2-Aminobenzonitriles and Donor-Acceptor Cyclopropanes.

Tetrahydro-4H-pyrrolo[3,2-c]quinolin-4-ones and dihydro-1H-benzo[b]azepines are efficiently synthesized from 2-aminobenzonitriles and donor-acceptor cyclopropanes mediated by SnCl4 in moderate to good yields. The reaction involves the initial ring opening of a cyclopropane ring due to activation by SnCl4 followed by nucleophilic attack by amine to give an adduct, which after unprecedented rearrangement at two different reaction temperatures provides two nitrogen heterocyclic compounds. This methodology can be used for the synthesis of hexahydropyrrolo[3,2-c]quinolinone derivatives, the structure of which is found in biologically active molecules.