Microwave-assisted Multicomponent Reaction Research Articles

Improved synthesis, molecular modeling and anti-inflammatory activity of new fluorinated dihydrofurano-naphthoquinone compounds

A series of new fluorinated dihydrofurano-napthoquinone compounds were sucessfully synthesized in good yields using microwave-assisted multi-component reactions of 2-hydroxy-1,4-naphthoquinone, fluorinated aromatic aldehydes, and pyridinium bromide. The products were fully characterized using spectroscopic techniques and evaluated for their anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Among 12 new compounds, compounds 8b, 8d, and 8e showed high potent NO inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 values ranging from 1.54 to 3.92 µM. The levels of pro-inflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 macrophages were remarkably decreased after the application of 8b, 8d, 8e and 8k. Molecular docking simulations revealed structure–activity relationships of 8b, 8d, and 8e toward NO synthase, cyclooxygenase (COX-2 over COX-1), and prostaglandin E synthase-1 (mPGES-1). Further physicochemical and pharmacokinetic computations also demonstrated the drug-like characteristics of synthesized compounds. These findings demonstrated the importance of fluorinated dihydrofurano-napthoquinone moieties in the development of potential anti-inflammatory agents.

Asymmetric synthesis of enantiopure tetracyclic dispirooxindolopyrrolidine-piperidones via microwave-assisted multicomponent reaction: Crystallographic analysis, antimicrobial activity and in silico studies

In an attempt towards the development of new antimicrobials, we synthesized by microwave-assisted multicomponent reaction (MCR) of enantiopure (E,E)-3,5-bisarylidene-N-[(S)-(-)-methylbenzyl]-4-piperidones, isatin and α-amino esters a series of optically active tetracyclic dispirooxindolopyrrolidine-piperidones. The beneficial and promising features of this protocol such as simple operational procedure, short reaction time (10 min), and high product yields (up to 97 %) make it an efficient eco-friendly approach offering a powerful mean to expand the structural diversity of spirooxindoles. This approach appears hugely advantageous for high-throughput screening processes in drug discovery research. In addition, crystallographic parameters and inter- and intramolecular interactions occurring in spiropyrrolidine-fused piperidone derivative 4g were examined through single-crystal XRD analysis allowing to determine the absolute configuration of the enantiopure compound. The preliminary biological assessment of their antimicrobial activity indicates that most of the screened products display higher activity than the standard reference drugs Ampicillin and Griseofulvin. Some of them exhibited good to moderate activity against both bacteria and fungi. In addition, in silico molecular docking and predictive ADMET studies for the most active spirocompounds were carried out. Molecular docking confirmed the binding efficacy of candidates 4c and 4l through low score energy values and the establishment of diverse bonding interactions with the active site residues. Finally, the ADMET profiling of the most active spiroheterocycles proved their remarkable drug-like and pharmacokinetic properties.

Alkoxy-functionalised dihydropyrimido[4,5-b]quinolinones enabling anti-proliferative and anti-invasive agents.

In this communication, we explored the synthesis of novel alkoxy-functionalised dihydropyrimido[4,5-b]quinolinones using a microwave-assisted multicomponent reaction. All the synthesized molecules were screened for anti-proliferative and anti-invasive activity against glioblastoma cells. 5c shows the most potent anti-proliferative activity with a half maximal effective concentration of less than 3 μM against primary patient-derived glioblastoma cells. 5c effectively inhibited invasion and tumor growth of 3D primary glioma cultures in a basement membrane matrix. This suggests that the novel compounds could inhibit both the proliferation and invasive spread of glioma and they were selected for further study.

Recent advances in microwave-assisted multicomponent synthesis of spiro heterocycles.

Spiro heterocycle frameworks are a class of organic compounds that possesses unique structural features making them highly sought-after targets in drug discovery due to their diverse biological and pharmacological activities. Microwave-assisted organic synthesis has emerged as a powerful tool for assembling complex molecular architectures. The use of microwave irradiation in synthetic chemistry is a promising method for accelerating reaction rates and improving yields. This review provides insights into the current state of the art and highlights the potential of microwave-assisted multicomponent reactions in the synthesis of novel spiro heterocyclic compounds that were reported between 2017 and 2023.

Insights into microwave assisted synthesis of spiro-chromeno[2,3-d]pyrimidines using PEG-OSO3H catalyst: DFT study and their antiproliferative activity

Herein, we established an environmentally benign green approach for the synthesis of new spirochromeno[2,3-d]pyrimidines. PEG-4000-OSO3H catalysed microwave-assisted multicomponent reaction of sesamol, isatin and barbituric acid enables us to produce spirochromeno[2,3-d]pyrimidines. This approach is notable for its eco-friendly polymer catalyst, rapid metal-free synthesis, easy workup, higher yield (88–97%), no need for column chromatographic purification and outstanding green credential parameters of the process. The use of harmless solvents, microwave process and reusability of reaction media made the present protocol sustainably effective from a green perspective. The molecular structure of 4j was confirmed by Single crystal XRD analysis and their DFT study was carried out. To gain insight into the molecule's geometry and physicochemical properties, quantum chemical density functional theory was employed at B3LYP/6–31G(d, p) basis set. Furthermore, all compounds were examined for antiproliferative activity against six solid human tumour cell lines. Compounds 4j and 4k exhibit excellent potency against T-47D (breast) and WiDr (colon) cell lines as compared to the standard drug cisplatin (CDDP). The most potent compound is 4j, which exhibits GI50 values in the range 5.2–11 µM against all cell lines.

Microwave produced 8-methyl-1,2,4,8-tetraazaspiro[4.5]dec-2-en-3-amine derivatives: their in vitro and in silico analysis.

Compound 1 is formed by a microwave-assisted multicomponent reaction of 1-methylpiperidin-4-one, 2-amino-4-methoxy-6-methyl-1,3,5-triazine, and thiosemicarbazide, followed by the synthesis of Schiff base 2a-l with a variety of aldehydes. A comparison was made between the conventional and microwave methods, and the microwave approach was shown to be considerably superior to the classical method since it takes less time and produces higher yields. Several spectral investigations, including 1H NMR, 13C NMR, Mass, and IR spectroscopy, are used to characterize the complete series. In vitro antibacterial testing suggests that compounds 2c, 2f, and 2g are promising antibacterial agents, although compounds 2d, 2e, and 2l are effective antimycobacterial agents when compared to the conventional medicine Rifampicin. The docking score from docking studies is considerable, which validates the results of the biological examination. Molecular docking was performed on Escherichia coli DNA gyrase. According to the in silico ADME analysis, each drug molecule is ideal for use in terms of drug solubility, hydrogen bonding, and cell permeability.

Synthesis, Molecular Docking, and Cytotoxic Evaluation of Fluorinated Podophyllotoxin Derivatives

Objective: The study was conducted to evaluate the in vitro and in silico anticancer activity of fluorinated podophyllotoxin derivatives. Methods: Microwave-assisted multicomponent reactions were carried out in an Anton Paar Microwave Synthetic Reactor Monowave 400 in order to synthesize fluorinated podophyllotoxin derivatives. These products were identified by spectral analysis and evaluated for their cytotoxicity against 4 types of human cancer cell lines (KB, HepG2, A549, and MCF7), as well as human embryonic kidney (Hek) 293 cells using MTT protocol. Molecular docking was conducted using 2 crystal structures of tubulin—colchicine (PDB ID: 4O2B) and topoisomerase II—etoposide (PDB ID: 3QX3) complexes. Results: Two potent cytotoxic fluorinated podophyllotoxin–naphthoquinone compounds were synthesized in good yields. They displayed high cytotoxic activity against all the tested cell lines, with IC50 values ranging from 0.58 to 3.17 µM. Notably, product 8a showed low toxicity against the Hek-293 cell line. Molecular docking results showed that products 8a and 8b participated in the same key interactions provided by etoposide with both topoisomerase and DNA chain domains. The binding energy values calculated for 8a and 8b are acceptable. Conclusion: This study revealed that products 8a and 8b exhibited promising in vitro and in silico anticancer activity and could be recognized as promising anticancer agents.

Synthesis of novel γ-butyrolactone-based phenazine compounds via microwave-assisted multicomponent domino reactions

Synthesis of novel γ-butyrolactone-based phenazine compounds via microwave-assisted multicomponent domino reactions

Microwave-assisted Multi-component Reaction for the Green Synthesis of Novel 4-(5-hydroxybenzo[a]phenazin-6-yl)-5-phenyl-1, 3-dihydro-2H-imidazol-2-one Using H3PW12O40@nano-TiO2 as Recyclable Catalyst

ABSTRACT In this context, we have demonstrated a highly efficient and green process for the preparation of various potentially biologically active functionalized 4-(5-hydroxybenzo[a]phenazin-6-yl)-5-phenyl-1,3-dihydro-2H-imidazol-2-one derivatives via a one-pot, the four-component cyclo-condensation reaction in the presence of catalytic amounts of phosphotungstic acid supported on TiO2 as a nontoxic, highly reactive, and eco-friendly solid acid catalyst under MWI in solvent-free conditions. The crystallinity and the crystallite size nano-TiO2 were fabricated and characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM), scanning electron microscopy (FESEM), Thermogravimetric Analysis (TGA), Fourier transform infrared (FT-IR), Brunauer-Emmett-Teller (BET), and atomic force microscopy (AFM). We believe that this work can provide new insights into the fabrication of high-performance photocatalysts and facilitate their practical application in environmental issues.

Microwave-assisted multicomponent reaction: An efficient synthesis of indolyl substituted and spiroxindole pyrido[2,3-d]pyrimidine derivatives

An efficient and catalyst-free protocol for the synthesis of a series of indole substituted or spiroxindole-consisted dihydropyrido[2,3-d]pyrimidine derivatives by one-pot three-component reaction of 2,6-diaminopyrimidin-4-one, various aryl aldehydes or isatins, and 3-cyanoacetyl indoles under microwave irradiation was investigated. The advantages of this methodology include high yields of products, short reaction time, easy work-up procedure and broad substrate scope.

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects.

Microwave-assisted (MWA) multicomponent reactions (MCRs) have successfully emerged as one of the useful tools in the synthesis of biologically relevant heterocycles. These reactions are strategically employed for the generation of a variety of heterocycles along with multiple point diversifications. Over the last few decades classical MCRs such as Ugi, Biginelli, etc. have witnessed enhanced yield and efficiency with microwave assistance. The highlights of MWA-MCRs are high yields, reduced reaction time, selectivity, atom economy and simpler purification techniques, such an approach can accelerate the drug discovery process. The present review focuses on the recent advances in MWA-MCRs and their mechanistic insights over the past decade and shed light on its advantage over the conventional approach.

Design and synthesis of new thiazoles by microwave-assisted method: Evaluation as an anti-breast cancer agents and molecular docking studies

A series of novel thiazole analogues were designed and synthesized by the microwave-assisted multicomponent reaction of thiocarbohydrazide, aldehydes with substituted phenacyl bromides. Structures of all the synthesized compounds were in good agreement with their spectral (1H and 13C NMR, FTIR, Mass) and analytical data. The target thiazole compounds were screened for their in vitro cytotoxic activity by testing against MCF-7, MDA-MB-231/ATCC, HS 578 T, BT-549, T-47D and MDA-MB-468 Breast cancer cell lines. From the in vitro results, it was found that the compound 4b has potent activity against MDA-MB-231/ATCC cell line. Docking studies were also done on these compounds to probe the possible binding site interactions which corroborated well with the in vitro results.

Synthesis and characterization of a composite organic semiconductor (curcumin-paracetamol/TiO2)

The aim of this work is to study some physical and chemical properties of an organic semiconductor (OSc)/ x%titanium dioxide (TiO2) heterosystem (with 0 ≤ x ≤ 20%) (OScs/ x%TiO2). The OSc is obtained from pure curcumin and paracetamol as starting molecules. The synthesis methodology of the mixtures of OScs/ x%TiO2 heterosystem involves a microwave-assisted multicomponent reaction using curcumin, paracetamol, and TiO2 as a heterogeneous solution. All mixtures were analyzed by Fourier-transform infrared spectroscopy, Raman spectroscopy, thermogravimetric analysis/differential thermal analysis, X-ray diffraction, ultraviolet–visible spectroscopy, and scanning electron microscopy. The results obtained show a new nanocomposite with interesting pharmaceutical, optical, electronic, and structural properties, which can be used in the fields of energy production, water purification, and air purification, as a biomaterial and for electronic applications.

A Review on Onychine and its Analogs: Synthesis and Biological Activity.

Onychine is a 4-azafluorenone alkaloid isolated from the Annonaceae family, in low concentrations. Onychine and its analogs exhibit a wide range of pharmacological activities such as antifungal, antibacterial, anticancer, and antimalarial. Because of the high bioactivity of some 4-azafluorenone derivatives, several synthetic methods have been developed for their procurement. Considering the importance of these alkaloids, we aim to present the main synthetic approaches to onychines and its derivatives and the biological activity of some 4-azafluorenones. The most prominent methodologies for the synthesis of onychines were reviewed. In this work, we cover many synthetic approaches for the synthesis of onychine and 4-azafluorenone derivatives including intramolecular cyclizations, multicomponent reactions, microwave-assisted multicomponent reactions, Diels-alder reactions, among others. Moreover, we also review the biological activity of 4-azafluorenones. 4-azafluorenones have risen as prominent structures in medicinal chemistry; however, most of the time, access to new derivatives involves toxic catalysts, harsh reaction conditions, and long-step procedures. Therefore, the development of new synthetic routes with more operational simplicity, simple purification procedure, good yields, and low environmental impact, is desirable.

Microwave-assisted Multi-component Domino Reaction for the Green Synthesis of Novel Benzo[a]pyrano[3',4':5,6]pyrano[2,3-c]phenazines Using H3PW12O40 as Efficient, Cost-effective and Recyclable Catalyst

In recent years, green chemistry techniques have attracted considerable attention in the chemical industry and academic research laboratories due to environmental, health, and economic benefits.1–5...

Microwave-assisted multicomponent reactions for rapid synthesis of AIE-active fluorescent polymeric nanoparticles by post-polymerization method

The development of simple and effective methods for synthesis of fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) plays an important role for the biomedical applications of AIE-active FPNs. In present work, we developed a facile strategy for the fabrication of AIE-active FPNs by a post-polymerization method based on the microwave-assisted Kabachnik–Fields (KF) reaction, which can conjugate with poly(PEGMA-NH2), AIE-active dye (TPE-CHO) and diethyl phosphate (DP) under microwave irradiation within 5min. The characterization results confirm that PEGMA-TPE FPNs are successfully prepared through the microwave-assisted KF reaction. The resultant AIE-active FPNs show high water dispersity, intensive fluorescence and low cytotoxicity. These features make these AIE-active FPNs great potential for biomedical applications. Moreover, the microwave-assisted KF reaction is simple, fast, atom economy that should be a general strategy for the fabrication of various multifunctional AIE-active FPNs. We believe this work will open up a new avenue for the preparation of AIE-active functional materials with great potential for different applications.

Microwave-assisted multicomponent reaction for the synthesis of 2-amino-4H-chromene derivatives using ilmenite (FeTiO3) as a magnetic catalyst under solvent-free conditions

A green and highly efficient method has been developed for the synthesis of 2-amino-4H-chromene derivatives in the presence of FeTiO3 as magnetic catalyst via one-pot three-component condensation reaction of aromatic aldehydes, malononitrile and α- or β-naphthol without solvent under microwave irradiation. Mild reaction conditions, short reaction times, simple work-up, use of an economically convenient catalyst, and excellent product yields are the advantageous features of this method. The catalyst can be easily recovered by a simple magnetic separation and can be recycled six times with no significant loss of catalytic activity.

Microwave-assisted one-pot three-component synthesis of imine 1,2,3-triazoles

A general and efficient methodology for the synthesis of novel triazoles has been developed based on a microwave-assisted multicomponent reaction involving α-thio aldehyde and propargylamine, with the formation of an imine that in situ reacts with organoazides by copper-catalyzed [3+2] azides–alkyne cycloaddition (CuAAC). The reaction results in a small library of imine 1,4-disubstituted 1,2,3-triazoles.

ChemInform Abstract: A Facile and Efficient Synthesis of Spiro[indoline‐3,5′‐pyrido[2,3‐d]pyrimidine] Derivatives via Microwave‐Assisted Multicomponent Reactions.

ChemInformVolume 46, Issue 24 Heterocyclic Compounds ChemInform Abstract: A Facile and Efficient Synthesis of Spiro[indoline-3,5′-pyrido[2,3-d]pyrimidine] Derivatives via Microwave-Assisted Multicomponent Reactions. Jing Wang, Jing Wang Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorJie Li, Jie Li Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorHongzhi Liu, Hongzhi Liu Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorZhou Xu, Zhou Xu Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorSonglei Zhu, Songlei Zhu Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this author Jing Wang, Jing Wang Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorJie Li, Jie Li Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorHongzhi Liu, Hongzhi Liu Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorZhou Xu, Zhou Xu Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this authorSonglei Zhu, Songlei Zhu Dep. Chem., Xuzhou Med. Coll., Xuzhou 221004, Peop. Rep. ChinaSearch for more papers by this author First published: 27 May 2015 https://doi.org/10.1002/chin.201524111Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue24June, 2015 RelatedInformation

Synthesis and structure–activity relationships of 4-fluorophenyl-imidazole p38α MAPK, CK1δ and JAK2 kinase inhibitors

The synthesis and structure–activity relationships of novel 4-(4′-fluorophenyl)imidazoles as selective p38α MAPK, CK1δ and JAK2 inhibitors with improved water solubility are described. Microwave-assisted multicomponent reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carboxylate and phosphonate groups were introduced via ‘click’ reactions. The kinase selectivity was influenced by the heteroaryl group at imidazole C-5 and the position of a carboxylic acid or tetrazole at imidazole C-2. For example, pyrimidines 15 and 34 inhibited p38α MAPK with IC50=250nM and 96nM, respectively. Pyridine 3 gave CK1δ inhibition with IC50=89nM and pyridin-2-one 31 gave JAK2 inhibition with IC50=62nM.