Synthesis Of Coumarins Research Articles

Synthesis and evaluation of novel ring-conjugated coumarins as biosafe broad-spectrum antimicrobial candidates

This study presents, for the first time, the synthesis of innovative conjugates identified as a five-membered ring integrating three heteroatoms linked linearly to the coumarin framework. Seven conjugates, comprising combinations of 1,3,2-dioxathiole-2-oxide and coumarin derivatives, were made via a three-stage synthetic procedure originating from benzene 1,2,4-triole. Spectroscopic methodologies, encompassing 1H-NMR, 13C-NMR, and FTIR, were utilized to validate the structural frameworks of the synthesized conjugates. Their capacity in the biomedicine field to act as broad-spectrum antimicrobial agents was evaluated. Furthermore, the biosafety and in silico pharmacokinetic characteristics of the conjugates were also examined. Six pathogenic aerobic bacteriomers, three anaerobic bacteriomers, and two fungiomers were utilized to investigate the broad-spectrum antimicrobial activity of the conjugates. On the other hand, three non-pathogenic bacteriomers were employed to reveal the biosafety profiles of the synthesized conjugates. Finally, two web-based programs were utilized to unveil the pharmacokinetic profiles of the title conjugates. The authors outlined four principal outcomes drawn from the extracted results. The conjugation between 1,3,2-dioxathiole-2-oxide and coumarin derivatives demonstrates biosafety and broad-spectrum antimicrobial implications. Conjugate DOTC5 displayed potent antibacterial activity against the tested aerobic bacteriomers, showing a potency comparable to that of the reference drug. Conjugate DOTC1 demonstrated strong antifungal activity exceeding that of the standard used. The synthesized conjugates, particularly DOTC5, displayed interesting biosafety profiles against the non-pathogenic bacteriomers. It concluded that the conjugates DOTC5 and DOTC1 exhibit the potential to function as valuable scaffolds for developing novel medications with biosafe, broad-spectrum antimicrobial activities in the foreseeable future.

Multicomponent reactions of cyanoacetanilide derivatives: Synthesis of coumarin and quinoline derivative and evaluations of their cytotoxicity

In this study, several fused heterocyclic systems involving tetrahydrobenzopyrans 7a-i and tetrahydrobenzopyridines 9a-i were synthesized. The reactions proceed via a multicomponent reaction of different aromatic aldehydes, cyanoacetanilide derivatives, and cyclohexane-1,3-dione. All the produced compounds were tested for their anticancer activity by using six cancer cell lines such as A549, HT-29, MKN-45, U87MG, SMMC-7721 and H460 utilizing foretinib as the positive control and the standard MTT assay in vitro. The results indicated that many synthesized derivatives were the most potent towards all the cancer cell lines used, six compounds 7e, 7f, 9b, 9d, 9e, and 9g showed the highest potency. The results obtained in this work enhance further investigations in the future.
 KEY WORDS: Multi-component reactions, Cyanoacetanilide, Pyran, Pyridine, Cytotoxicity
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 739-750. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.15

Synthesis, Characterization, Thermal and Dielectric Properties of Amino Acid-Centered Coumarin and Chalcone Hybrid Structures Via Click Reaction

Bu çalışma, kalkon ve kumarin grupları içeren amino asit konjugatlarının dielektrik özellikleri ve termal kararlılıklarının karşılaştırmalı bir analizini içermektedir. Bu konjugatların elektriksel davranışını incelemek amacıyla dielektrik sabiti, dielektrik kaybı ve AC iletkenliği araştırılırken, termal kararlılıklarını incelemek için termogravimetrik analiz (TGA) kullanılmıştır. Konjugatlar, kalkon veya kumarin yapılarının amino asit omurgalarına klik kimyası ile dahil edilmesiyle sentezlenmiştir. Dielektrik sabiti ölçümleri, kumarin bazlı amino asit konjugatlarının, kumarin sisteminin genişletilmiş π-konjugasyonu ve polarize edilebilirliği nedeniyle kalkon bazlı konjugatlara kıyasla daha yüksek değerler sergilediğini ortaya koymuştur. Dielektrik kayıp analizi, her iki konjugat türünün de yük transfer süreçleri ve moleküler hareketlerle ilişkili kayıplar sergilediğini göstermiştir. TGA ile termal stabilite değerlendirmesi, kalkon içeren konjugatın daha yüksek bozunma sıcaklıkları ile iyi termal stabilite sergilediğini ortaya koymuştur. Yüksek sıcaklıklarda gözlenen ağırlık kaybı, organik bileşenlerin termal bozunmasını göstermiştir. Bu etkili sonuçlar, dielektrik sabiti, dielektrik kaybı ve AC iletkenliği dahil olmak üzere dielektrik özelliklerin yanı sıra kalkon veya kumarin içeren amino asit konjugatlarının termal kararlılığı hakkında değerli bilgiler sağlamaktadır. Bulgular, elektronik cihazlar ve fonksiyonel malzemelerdeki potansiyel uygulamalar için önemli olan elektriksel davranışlarının ve termal özelliklerinin anlaşılmasına katkıda bulunmaktadır..

Recent Trends in the Synthesis and Bioactivity of Coumarin, Coumarin-Chalcone, and Coumarin-Triazole Molecular Hybrids.

Molecular hybridization represents a new approach in drug discovery in which specific chromophores are strategically combined to create novel drugs with enhanced therapeutic effects. This innovative strategy leverages the strengths of individual chromophores to address complex biological challenges, synergize beneficial properties, optimize pharmacokinetics, and overcome limitations associated with single-agent therapies. Coumarins are documented to possess several bioactivities and have therefore been targeted for combination with other active moieties to create molecular hybrids. This review summarizes recent (2013-2023) trends in the synthesis of coumarins, as well as coumarin-chalcone and coumarin-triazole molecular hybrids. To cover the wide aspects of this area, we have included differently substituted coumarins, chalcones, 1,2,3- and 1,2,4-triazoles in this review and considered the point of fusion/attachment with coumarin to show the diversity of these hybrids. The reported syntheses mainly relied on well-established chemistry without the need for strict reaction conditions and usually produced high yields. Additionally, we discussed the bioactivities of the reported compounds, including antioxidative, antimicrobial, anticancer, antidiabetic, and anti-cholinesterase activities and commented on their IC50 where possible. Promising bioactivity results have been obtained so far. It is noted that mechanistic studies are infrequently found in the published work, which was also mentioned in this review to give the reader a better understanding. This review aims to provide valuable information to enable further developments in this field.

Transcriptomic and targeted metabolome analyses revealed the regulatory mechanisms of the synthesis of bioactive compounds in Citrus grandis 'tomentosa'.

Exocarpium Citri Grandis is a popular Chinese herbal medicine prepared from Citrus grandis 'tomentosa', and it is rich in several bioactive compounds, including flavonoids, coumarins, and volatile oils. However, studies are yet to elucidate the mechanisms of synthesis and regulation of these active components. Therefore, the present study examined the profiles of flavonoids and volatile oil bioactive compounds in plant petals, fruits, and tender leaves, and then performed RNA sequencing on different tissues to identify putative genes involved in the synthesis of bioactive compounds. The results show that the naringin, naringenin, and coumarin contents of the fruitlets were significantly higher than those of the tender leaves and petals, whereas the tender leaves had significantly higher levels of rhoifolin and apigenin. A total of 49 volatile oils, of which 10 were mainly found in flowers, 15 were mainly found in fruits, and 18 were mainly found in leaves, were identified. RNA sequencing identified 9,942 genes that were differentially expressed in different tissues. Further analysis showed that 20, 15, and 74 differentially expressed genes were involved in regulating flavonoid synthesis, regulating coumarin synthesis, and synthesis and regulation of terpenoids, respectively. CHI1 (Cg7g005600) and 1,2Rhat gene (Cg1g023820) may be involved in the regulation of naringin synthesis in C. grandis fruits. The HDR (Cg8g006150) gene, HMGS gene (Cg5g009630) and GGPS (Cg1g003650) may be involved in the regulation and synthesis of volatile oils in C. grandis petals. Overall, the findings of the present study enhance our understanding of the regulatory mechanisms of secondary metabolites in C. grandis, which could promote the breeding of C. grandis with desired characteristics.

Syntheses, reactivity, and biological applications of coumarins.

This comprehensive review, covering 2021-2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis and functionalization of coumarins have advanced with innovative strategies. This enabled the incorporation of diverse functional fragments or the construction of supplementary cyclic architectures, thereby the biological and physico-chemical properties of the compounds obtained were enhanced. The unique chemical structure of coumarine facilitates binding to various targets through hydrophobic interactions pi-stacking, hydrogen bonding, and dipole-dipole interactions. Therefore, this important scaffold exhibits promising applications in uncountable fields of medicinal chemistry (e.g., neurodegenerative diseases, cancer, inflammation).

An Update on Recent Green Synthetic Approaches to Coumarins

Abstract: Coumarin and its derivatives are privileged heterocyclic motifs and important building blocks for developing the biologically active compound due to its significant role in the development of new drugs. As a result, many methodologies have been developed to synthesize this important class of compounds. However, some methods are associated with toxic and corrosive catalysts, longer reaction time, poor yield, less purity, and by-products along with the desired product. In order to minimize the utilization and generation of toxic organic substances, green synthetic methods are applied in this manner. Green chemistry methods cover a wide range of methods, including the application of ultrasound and microwaves, ionic liquids and deep eutectic solvents, solvent-free and catalyst-free synthesis, and mechanosynthesis. These green synthetic methods have successfully performed all typical condensation reactions for coumarin synthesis like Knoevenagel, Perkin, Kostanecki-Robinson, Pechmann, and Reformatsky reactions. Compared to conventional methods, these methods not only minimize the use and generation of harmful chemicals but also improve reaction efficiency in terms of product yields, purity, energy consumption, and post-synthetic procedures. Due to the implication of coumarin (2-oxo-2H-1-benzopyran) backbone as a biologically active ubiquitous fragment and the recent demands of reducing toxic solvents, catalysts, and energy consumption, this review summarized various green synthetic methods for coumarin synthesis. Moreover, researchers working on this coumarin scaffold synthesis can find handy information from this review on the green synthetic approaches to their synthesis.

Diazene-Catalyzed Oxidative Alkyl Halide-Olefin Metathesis.

The first platform for oxidative alkyl halide-olefin metathesis is described. The procedure employs diazenes as catalysts, which effect the cyclization of alkenyl alkyl halides to generate cyclic olefins and carbonyl products. The synthesis of phenanthrene, coumarin, and quinolone derivatives is demonstrated as well as the potential to apply this strategy to other electrophiles.

Correction to: Novel green sulfated phosphotungstic acid supported on MCM-41-coated NiFe2O4 MNPs for xanthene and coumarin synthesis

Correction to: Novel green sulfated phosphotungstic acid supported on MCM-41-coated NiFe2O4 MNPs for xanthene and coumarin synthesis

Synthesis and Structural Elucidation of P-stereogenic Coumarins

This paper presents the general synthesis of a comprehensive group of P-chiral phosphinyl derivatives with a natural coumarin-type motif. A chiral substituent was attached at the third position of the coumarin molecule via the Knoevenagel procedure using readily available P-chiral phoshinylacetic acid esters without loss of enantiomeric purity. The application of salicylaldehyde-based derivatives allowed the incorporation of substituents of different electron character into the backbone of these coumarins making them suitable for subsequent chemical modifications. As a result, we gained access to six achiral (2a–g) and a large number ((Sp)-4a–f, (Sp)-6a–e and (Rp)-8a) of new potential chiral ligand precursors, pharmaceuticals, etc. with an imbedded phosphinyl group with evidenced biological activity based on the natural coumarin backbone. The molecular structure, including absolute configuration, was determined for seven compounds.

Novel butane sulfonic acid-functionalized core–shell magnetic nanocatalysts for ultrasound-assisted coumarin synthesis

Novel Fe3O4@C@PrNH@BuSO3H NPs were formulated, fabricated, and used as an efficient nanocatalyst in coumarin synthesis under ultrasound and conventional conditions.

Regulatable selective synthesis of benzofurans and coumarins from aryl propargyl ethers via an electrochemical tandem cyclization reaction

A divergent protocol for the selective synthesis of benzofuran-2-carboxaldehydes and 3-organoselenyl-2H-coumarins from propargylic aryl ethers in the presence of dialkyl(aryl) diselenides under electrochemical reaction conditions was established.

Anthelmintic and anti-filarial coumarins of natural and synthetic origin: Chemical and biological intervention

Coumarin is a bicyclic system with a lactone-(hetero)aryl motif and a critical structural unit of many natural and synthetic pharmaceutical compounds. The coumarins possess a broad spectrum of biological activities and have successful clinical applications. Several coumarin-based natural compounds like osthol, isopimpinellin, umbelliferon, scopoletin, scopoline, cleomiscosin A to D, and inophyllum E have been isolated with anthelmintic and antifilarial activities. The ability of coumarin to interact with various active sites through noncovalent interactions like van der Waals forces, metal coordination, electrostatic and hydrophobic interaction, as well as hydrogen bonding, have led to the synthesis of different coumarins with significant anthelmintic and anti-filarial activities. The SAR studies of parasitic coumarins revealed that a hydroxy group at C-4 and C-7 positions has a deciding role in the anthelmintic and anti-filarial activity. The careful structure–activity studies could be effectively employed in the structural optimization of the bicyclic coumarin ring, allowing it to have many derivatives that could be screened for helminthiases. We hope this review will provide a structure-based input to researchers to design and develop novel coumarin hybrids to treat helminthiasis and filariasis.

Synthesis and pharmacological evaluation of novel coumarin based triazolyl glycoconjugates as potential antibacterial and anti-proliferative agents

Synthesis and pharmacological evaluation of novel coumarin based triazolyl glycoconjugates as potential antibacterial and anti-proliferative agents

Transcriptional insights of citrus defense response against Diaporthe citri

Citrus melanose, caused by Diaporthe citri, is one of the most important and widespread fungal diseases of citrus. Previous studies demonstrated that the citrus host was able to trigger the defense response to restrict the spread of D. citri. However, the molecular mechanism underlying this defense response has yet to be elucidated. Here, we used RNA-Seq to explore the gene expression pattern at the early (3 days post infection, dpi) and late (14 dpi) infection stages of citrus leaves in response to D. citri infection, and outlined the differences in transcriptional regulation associated with defense responses. The functional enrichment analysis indicated that the plant cell wall biogenesis was significantly induced at the early infection stage, while the callose deposition response was more active at the late infection stage. CYP83B1 genes of the cytochrome P450 family were extensively induced in the callus deposition-mediated defense response. Remarkably, the gene encoding pectin methylesterase showed the highest upregulation and was only found to be differentially expressed at the late infection stage. Genes involved in the synthesis and regulation of phytoalexin coumarin were effectively activated. F6’H1 and S8H, encoding key enzymes in the biosynthesis of coumarins and their derivatives, were more strongly expressed at the late infection stage than at the early infection stage. Collectively, our study profiled the response pattern of citrus leaves against D. citri infection and provided the transcriptional evidence to support the defense mechanism.

Thermosonication-Catalyzed Synthesis of New 3-Esterified Coumarins as Biocompatible Antitumor Candidates

Thermosonication-Catalyzed Synthesis of New 3-Esterified Coumarins as Biocompatible Antitumor Candidates

Synthesis and Fluorescence Properties of Imidazopyridine-Linked Coumarins via Tandem C(sp2)-H Functionalization/Decarboxylation Reaction.

A catalyst-, oxidant-free and green synthetic route for direct access to a series of novel imidazopyridine-linked coumarins has been devised through tandem C(sp2)-H functionalization/decarboxylation reaction in ethyl acetate as a sustainable medium. Moreover, the utilities of ensured products in further organic synthesis were conducted by Suzuki-Miyaura and Sonogashira cross-coupling reactions. The fluorescence characteristics of the produced molecules are appropriate, and the synthesized scaffolds could promisingly garner future attention in clinical diagnostics and bioimaging research.

Synthesis and biological evaluation of coumarin appended thiazole hybrid heterocycles: Antibacterial and antifungal study

In the present investigation, a series of 3-(1-(2-(thiazol-2-yl)hydrazineylidene)ethyl)-2H-chromen-2-one derivatives are synthesized in good to excellent yield using PEG-400 as a reaction medium. The synthesized compounds are characterized by using different spectroscopic methods like FT-IR, 1H NMR, 13CMR, and HRMS. In this study, the synthesis and biological evaluation of a series of coumarin-appended thiazole hybrids were explored to assess their antibacterial and antifungal properties. Antibacterial activity of the synthesized coumarin-thiazole hybrids was screened against E. coli, P. aeruginosa, S. aureus, and S. pyogenes strains, while antifungal activity was screened against C. albicans, A. niger, and A. clavatus strains. Some of the synthesized compounds showed good antibacterial activity against E. coli and P. aeruginosa strains compared to standard drugs. The ADME profile of these compounds showed favorable pharmacological properties.

Towards Platinum(II) Complexes forin celluloApplications: Synthesis, Characterization, Biological and Catalytic Evaluation

AbstractWith the aim of achieving bioorthogonal intracellular catalysis, a library of platinum(II) complexes was synthesized. Their non‐toxicity to living cells was demonstrated and their catalytic activity was evaluated on a cyclization reaction leading to a highly fluorescent coumarin. None of the platinum complexes showed any catalytic activity for coumarin synthesis. Still, we demonstrated that the silver salt AgSbF6commonly used to ‘activate’ metal catalysts by removing a chloride is a very efficient catalyst for the studied intramolecular cyclization reaction.

Synthesis of anthracene linked polycyclic pyridine derivatives fused with coumarin and pyrazole by one‐pot multicomponent strategy followed by oxidation

AbstractA simple, metal‐free, and effective methodology has been developed for the synthesis of coumarin and pyrazole‐fused polycyclic pyridine derivatives. This synthesis was achieved in two steps. In the first step, polycyclic fused dihydropyridine derivatives were synthesized by a one‐pot three‐component reaction of 9‐anthracene carboxaldehyde/2‐naphthaldehyde, 4‐hydroxycoumarin, and 3‐amino pyrazole in acetonitrile using a catalytic amount of p‐TSA under reflux conditions. Then, these synthesized products were further oxidized into their corresponding pyridine derivatives using 10 mol% of molecular iodine as a catalyst in DMSO at 100°C. Metal‐free reaction conditions, good yields, simple purification process, operational simplicity, and inclusion of more than one bioactive moiety such as coumarin, pyrazole, pyridine, and anthracene/naphthalene in the product are the distinguishing features of this methodology.