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A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%. [ABSTRACT FROM AUTHOR]

The fungus Xylaria sp. Z184, harvested from the leaves of Fallopia convolvulus (L.) Á. Löve, has been isolated for the first time. Chemical investigation on the methanol extract of the culture broth of the titles strain led to the discovery of three new pyranone derivatives, called fallopiaxylaresters A–C (1–3), and a new bisabolane-type sesquiterpenoid, named fallopiaxylarol A (4), along with the first complete set of spectroscopic data for the previously reported pestalotiopyrone M (5). Known pyranone derivatives (6–11), sesquiterpenoids (12–14), isocoumarin derivatives (15–17), and an aromatic allenic ether (18) were also co-isolated in this study. All new structures were elucidated by the interpretation of HRESIMS, 1D, 2D NMR spectroscopy, and quantum chemical computation approach. The in vitro antimicrobial, anti-inflammatory, and α-glucosidase-inhibitory activities of the selected compounds and the crude extract were evaluated. The extract was shown to inhibit nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, with an inhibition rate of 77.28 ± 0.82% at a concentration of 50 μg/mL. The compounds 5, 7, and 8 displayed weak antibacterial activity against Staphylococcus areus subsp. aureus at a concentration of 100 μM. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Ten novel isocoumarins, including four pairs of enantiomers, were isolated from Artemisia dubia var. subdigitata (Asteraceae). Compounds 1, 2 and 3a/3b possessed a unique 6/6/6‐tricyclic system comprising an unusual 1‐(2‐methylcyclohexyl) propan‐1‐one moiety fused with isocoumarin core skeleton. Compounds 4a/4b were characterized as an unexpected 2,5‐dimethylcyclohexan‐1‐one scaffold, and compounds 5a/5b and 6a/6b were rare 1,2‐seco‐isocoumarin. Their structures and absolute configurations were elucidated through spectroscopic data, X‐ray crystallography, ECD and NMR calculations with DP4+ analyses. Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin. Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and PI3K‐Akt signaling pathway. The molecular docking revealed that compound 1 had high binding affinity with CDK2 (total score: 6.8717). Furthermore, compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines, with inhibitory ratios of 85.1% and 84.5% (HepG2), 88.2% and 87.3% (Huh7), and 69.2% and 69.1% (SK‐Hep‐1) at 200 μmol·L–1, respectively. [ABSTRACT FROM AUTHOR]

Herein, we describe metal‐free fluorocyclization of 2‐alkynylbenzoates by N‐fluoropyridinium salts. The present method allows the selective synthesis of 4‐fluoroisocoumarins and 3,4,4‐trifluoroisochromanones by minor modification of the reaction conditions. [ABSTRACT FROM AUTHOR]

Chronic inflammation plays a crucial role in the development and progression of numerous chronic diseases. To search for anti-inflammatory metabolites from endophytic fungi isolated from plants growing in Thai mangrove areas, a chemical investigation of those fungi was performed. Five new oxygenated isocoumarins, setosphamarins A–E (1–5) were isolated from the EtOAc extract of an endophytic fungus Setosphaeria rostrata, along with four known isocoumarins and one xanthone. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of the undescribed compounds were established by comparative analysis between experimental and calculated circular dichroism (ECD) spectroscopy. All the compounds were evaluated for their anti-inflammatory activity by monitoring nitric oxide inhibition in lipopolysaccharide-induced macrophage J774A.1 cells. Only a xanthone, ravenelin (9), showed potent activity, with an IC50 value of 6.27 μM, and detailed mechanistic study showed that it suppressed iNOS and COX-2 expression. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of isocoumarins using Rhodium (Rh) complexes as catalysts. The authors explore the use of phenacyl phosphoniums and iodonium ylides as building blocks in this process. They present their experimental findings, optimization of reaction conditions, and the scope of the reaction with various phenacyl phosphoniums. The research provides valuable insights into the synthesis of isocoumarins using Rh-catalyzed C-H activation. Additionally, the document provides detailed information on the synthesis and characterization of specific compounds, including their chemical structures, yields, physical properties, and spectroscopic data. [Extracted from the article]

Herein, we report a facile and proficient protocol for the synthesis of 4‐bromoisocoumarins through brominative annulation of 2‐alkynylaryloate esters with in situ generated bromoiodane using a simple hypervalent iodine reagent as mild oxidant and potassium bromide as the halogen source. Using this method, a broad range of valuable halogenated isocoumarins can be obtained in excellent yields at room temperature. Also, this reaction takes place in the absence of any metal catalyst and exhibits high functional group tolerance. Besides, the reaction can also be extended to the gram scale, and a catalytic approach was also demonstrated. Additionally, the prepared 4‐bromoisocoumarins were further transformed into important synthetic compounds. [ABSTRACT FROM AUTHOR]

We have developed an efficient and straightforward method for the construction of the derivatives of 4-(arylthio)isochromenones via hydrogen bonding network-assisted sulfenylation and electrophilic cyclization by using electrophilic N-thiosuccinimides and 2-silynylbenzoates. Hexafluoroisopropanol as a promoter is indispensable in this catalyst-free protocol. Besides, the silyl group was crucial for the successful transformation. [ABSTRACT FROM AUTHOR]

Keywords: ruthenium catalysis; mandelic acids; alkynes; annulation; isocoumarins EN ruthenium catalysis mandelic acids alkynes annulation isocoumarins 2005 2010 6 10/09/23 20231024 NES 231024 Graph Isocoumarins are an important class of natural lactones, and their skeletal structure is an important part of many active pharmaceutical ingredients. At present, the major methods for synthesizing isocoumarins include (1) the cyclization reaction of I ortho i -halogen-substituted benzoic acids or their esters or amides with 1,3-diketones or internal alkynes; [10][11][12] and (2) the internal cyclization reaction of I ortho i -alkenyl- or alkynyl-substituted benzoic acids or their esters. The reactions of benzaldehydes B 5 b and benzoic acids B 6 b with B 2a b proceeded when the amount of Cu(OAc) SB 2 sb -H SB 2 sb O was increased to 1.5 equivalents and the reaction time was shortened to ten hours. Ruthenium(II)-Catalyzed C-H Annulation of Mandelic Acids with Internal Alkynes to Construct Isocoumarins. [Extracted from the article]

Isoquinolones and isoquinolines are crucial natural and synthetic heterocyclic compounds exhibiting a range of biological activities. A less explored strategy for the recyclization of isocoumarins to isoquinolones involves the transformation of 1H‐isochromen‐1‐ones with a carbonyl group at position 3 using primary amines. This study presents a straightforward one‐pot protocol for the recyclization of 3‐acetyl‐ and 3‐benzoylisocoumarins into their corresponding isoquinolone derivatives using structurally diverse primary amines. This provides versatile and scalable routes for accessing a variety of 2‐R‐isoquinolin‐1(2H)‐ones. Interestingly, the acyl group also reacted with the hydroxyl group of 2‐aminoethanol, leading to the simultaneous formation of 3,4‐dihydro[1,4]oxazino[4,3‐b]isoquinolin‐6(1H)‐ones alongside lactone recyclization. Moreover, the recyclization process was accompanied by more complex alternative cyclizations, including an oxidative‐reductive stage. For instance, the recyclization of isocoumarins with benzylamine resulted in the formation of isochromeno[3,4‐c]pyrroles, whereas with glycine derivatives, 1,2‐dihydro‐6H‐pyrazino[1,2‐b]isoquinolin‐3,6(4H)‐diones were obtained. [ABSTRACT FROM AUTHOR]

Isocoumarins and dihydroisocoumarins are important skeletons with a wide range of biological activities, such as anti-bacterial, anti-allergy, anti-fungal, anti-tumor, and anti-HIV properties. Herein, we demonstrated divergent syntheses of isocoumarins and 3,4-dihydroisocoumarins by intramolecular dehydrogenative cyclization of 2-(3-oxobutyl) benzoic acids. This transformation undergoes Csp3–H bonds and O–H bonds coupling in air using copper salt. The reactions may undergo free radical process. [ABSTRACT FROM AUTHOR]

A new coumarin, methyl (E)-4-((6-methoxy-2-oxo-2H-chromen-7-yl)oxy)-2-methylbut-2-enoate (1), has been isolated from the rhizomes of Polygonatum chingshuishanianum, together with six known compounds – scopoletin (2), rutin (3), isoquercetin (4), hyperoside (5), (3R)-5,7-dihydroxy-3-(2′,4′-dihydroxybenzyl)-chroman-4-one (6), and (3R)-5,7-dihydroxy-6-methoxy-8-methyl-3-(2′,4′-dihydroxybenzyl)-chroman-4-one (7). The structure of new compound 1 was determined through spectroscopic and MS analyses. Among the isolates compounds 3–6 showed potent inhibition with IC50 values of 10.25 ± 0.75, 17.60 ± 1.28, 18.82 ± 1.63, and 24.93 ± 2.07 μM, respectively, against LPS-induced NO generation. [ABSTRACT FROM AUTHOR]

[Display omitted] 6-Substituted isocoumarins with aryl, alkynyl, and diphenyl-amino substituents were synthesized from 4-bromobenzoic acid by annulation with tolane via rhodium-catalyzed C–H activation followed by palladium-catalyzed cross-coupling reactions. The compounds obtained exhibit luminescence emission in the violet–blue region (370–480 nm) with quantum yields up to 95% (for the diphenylamino derivative). Aggregation of biphenyl-substituted isocoumarin leads to a strong bathochromic shift (by 80 nm) of emission as a result of intermolecular π–π stacking interactions. [ABSTRACT FROM AUTHOR]

An endophytic fungus identified as Aspergillus carbonarius was obtained from from sea sponge Aaptos suberitioides. Phytochemical study of fungal A. carbonarius led to the isolation of four compounds (1-4) of which compound 1 was a new isocoumarin derivative, (R)- 6-hydroxy-3-(1-hydroxypropan-2-yl)-8-methoxyisocoumarin. The others (compounds 2-4) were the known compounds. Isolation of these compounds was performed using vacuum liquid dan column chromatography. The structure elucidation and identification of these compounds were conducted with the help of NMR and HR-ESI-MS spectroscopic data. All isolated compounds (1-4) were tested for their antibacterial activity against five bacterial strains and displayed inactive activity against all tested microorganisms. [ABSTRACT FROM AUTHOR]

The assembly of isocoumarins starting from easily available N,N-dimethyl enaminones and iodonium ylides via a Rh(III)-catalyzed C–H bond activation/annulation cascade reaction is herein described. This protocol proceeds under mild conditions and provides access to a wide variety of isocoumarin derivatives in good to excellent yields with good functional group compatibility. Furthermore, the gram-scale synthesis and various further chemical transformations enhance its synthetic utility. [ABSTRACT FROM AUTHOR]

Fungi in the genus Talaromyces occur in every environment in both terrestrial and marine contexts, where they have been quite frequently found in association with plants and animals. The relationships of symbiotic fungi with their hosts are often mediated by bioactive secondary metabolites, and Talaromyces species represent a prolific source of these compounds. This review highlights the biosynthetic potential of marine-derived Talaromyces strains, using accounts from the literature published since 2016. Over 500 secondary metabolites were extracted from axenic cultures of these isolates and about 45% of them were identified as new products, representing a various assortment of chemical classes such as alkaloids, meroterpenoids, isocoumarins, anthraquinones, xanthones, phenalenones, benzofurans, azaphilones, and other polyketides. This impressive chemodiversity and the broad range of biological properties that have been disclosed in preliminary assays qualify these fungi as a valuable source of products to be exploited for manifold biotechnological applications. [ABSTRACT FROM AUTHOR]

In this study, Rh(III)‐catalyzed C−H bifunctionalization and direct vinylene annulation of sulfoxonium ylides and N‐carbamoylindoles with vinylene carbonate was accomplished, which afforded a series of naphthalenones containing a β‐ketosulfoxonium ylide moiety, isocoumarins, and pyrimidones. This protocol featured mild conditions, broad substrate scope, and functional‐groups compatibility. In addition, related applications and preliminary mechanistic exploratory were also investigated [ABSTRACT FROM AUTHOR]

This study reports the isolation and identification of the endophytic fungus Exserohilum rostratum through molecular and morphological analysis using optical and transmission electron microscopy (TEM), as well as the procurement of its secondary metabolite monocerin, an isocoumarin derivative. Considering the previously observed biological activities of monocerin, this study was performed on human umbilical vein endothelial cells (HUVECs) that are widely used as an in vitro model for several different purposes. Important parameters, such as cell viability, senescence-associated β-galactosidase, cellular proliferation by using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE), apoptosis analysis with annexin, cellular morphology through scanning electron microscopy (SEM), and laser confocal analysis were evaluated after exposing the cells to monocerin. After 24 h of exposure to monocerin at 1.25 mM, there was more than 80% of cell viability and a low percentage of cells in the early and late apoptosis and necrosis. Monocerin increased cell proliferation and did not induce cell senescence. Morphological analysis showed cellular integrity. The study demonstrates aspects of the mechanism of action of monocerin on endothelial cell proliferation, suggesting the possibility of its pharmaceutical application, such as in regenerative medicine. [ABSTRACT FROM AUTHOR]

In this research, the corresponding isocoumarin derivatives have been synthesized by tandem intramolecular cyclization of methyl 2-(phenylethynyl)benzoate 1 with ethyl acrylate. This process involves the synthesis of compounds 3-9 from compound 1 and 2 in one-pot reaction and zinc triflate as catalyst. The antioxidant properties of the synthesized isocoumarin have also been investigated by DPPH method. [ABSTRACT FROM AUTHOR]

The versatility of isocoumarin frameworks offers the privilege to access many pharmacological targets. This unique heterocycle core present in many natural products and complex organic molecules contribute to medicinal chemistry as anti‐cancer, anti‐inflammatory and immunomodulatory agents. The attractive properties exhibited by its analogues urged the scientists to explore their synthetic analogues. In regard to the myriads of synthetic methodologies, we have compiled a review update covering all the articles that have been published towards the synthesis of 3‐substituted and 3,4‐disubstituted isocoumarins. Additionally, we have also highlighted a systematic survey of catalytic methods for their synthesis along with their scope towards diverse functionalizations and plausible mechanistic aspects. [ABSTRACT FROM AUTHOR]

Two new isocoumarins, 5-(2-hydroxyethyl)-7-methoxy-3-(2-oxopropyl)-1H-isocoumarin (1), 7-methoxy-5-methyl-3-(2-oxopropyl)-1H-isocoumarin (2), along with four known ones, were isolated from the fermentation products of an endophytic fungus Aspergillus oryzae derived from cigar tobacco. Their structures were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited anti-TMV activities with inhibition rates of 36.2 and 32.8% at a concentration of 20 μmol/mL, respectively, compared with 35.6% for positive control ningnanmycin. [ABSTRACT FROM AUTHOR]

The marine-derived fungus SCZ-1 was cultured on rice solid medium. The fermented materials was extracted using ethyl acetate to afford an extract, which was separated by repeated column chromatography to afford three polyketides and five alkaloids, including 2 new polyketides (1 and 2). The known compounds were identified to be penipyrol A (3), cyclopenin (4), cyclopenol (5), terretrione D (6), viridicatol (7), and viridicatin (8). The structures of 1 and 2 were determined by extensive analyses of spectroscopic data (1D and 2D NMR, and HRESIMS). The absolute configuration of 2 was assigned by comparison of the experimental ECD spectrum with calculated ECD spectrum. Compound 1, bearing a two-carbon side chain at C-2, is seldom found among natural isocoumarins. All metabolites were screened for their inhibitory effects toward α-glucosidase, only compound 8 showed weak activity with an IC50 value of 548 μM. [ABSTRACT FROM AUTHOR]

Agrimonolide (AM), which is a derivative of isocoumarins, is found mainly in the herb Agrimonia pilosa Ledeb. This compound is highly lipophilic and readily crosses the blood–brain barrier. In recent years, interest has grown in the use of AM as a multitarget natural treatment for various diseases, such as cancer, inflammation, hepatic injury, myocardial damage, and diabetes mellitus. The potential mechanisms of these pharmacological effects have been clarified at cellular and molecular levels. AM shows no cytotoxicity over a range of concentrations in different types of cells, providing evidence for its good safety profile in vitro. These findings indicate that AM is a promising medicinal agent. However, most studies on AM's pharmacological activities, mechanisms of action, and safety lack substantial animal or human data. Additionally, the pharmacokinetics, metabolism, and disposition of this compound have received little attention. This review highlights the status of current information regarding the sources, properties, pharmacological effects, and safety of AM. Furthermore, potential strategies to resolve problematic issues identified in previous studies are fully discussed. This summary and analysis of the research progress of AM may inspire deeper investigations and more extensive applications of AM in the future. [ABSTRACT FROM AUTHOR]

This work demonstrates the influence of the catalyst and alkyne nature on the regioselectivity of rhodium-catalyzed annulation of alkoxy-substituted benzoic acids (such as 3-methoxybenzoic, 3,4-dimethoxybenzoic, and piperonylic acids) with alkynes. Here, X-ray diffraction and DFT calculation data gave evidence that the observed regioselectivity is provided by both steric and coordination effects of methoxy groups. The latter is the result of weak non-covalent C–H⋯O interactions with the supporting ligand rather than with the rhodium atom. We believe that these results are also valid for other reactions of the C-H activation of methoxy-substituted arene compounds. [ABSTRACT FROM AUTHOR]

A series of new noscapinoids designed; synthesized and assessed whether its 3‐ylidenephthalide and isocoumarin conjugates improved cytotoxicity. Cu‐catalysed Sonogashira coupling of N‐propargyl noscapine with 2‐bromobenzoic acids followed by in‐situ substrate‐directed 5‐exo‐dig or 6‐endo‐dig cyclization produced 3‐ylidenephthalide 6 a–6 f and isocoumarin 7 a–7 h analogues in very good yields. In comparison to the lead drug, noscapine, all the newly synthesised derivatives exhibited strong cytotoxic potential in vitro with IC50 ranging from 5.4 μM to 39.5 μM across the evaluated panel of cancer cell lines, without harming normal cells (IC50 >300 μM). [ABSTRACT FROM AUTHOR]

As pyrazoles are familiar for showing various biological properties, a series of novel isocoumarin tethered carbothioamide linked pyrazole derivatives were prepared successfully in the presence of environmental favor conditions and evaluated for their pathogenic resistance against four bacteria and two fungi, showing significant activity against different microbial except compound 5d. Among the active compounds, 5f displayed highest antimicrobial property. In fact, 5b and 5l motifs showing good inhibitory activity. Further, a detailed structure activity relationship also discussed, which revealed that the presence of electron withdrawing -NO2 group in 5f compound may delivered highest biological property, while the amino group attached in compound 5d delivered inactive antibacterial property. Moreover, computer aided studies of biologically effective compounds to determine the interactions and docking score with the crystal structure of Escherichia coli 24 kDa DNA gyrase subunit B in complex with clorobiocin. It was observed that the amino acid residues present in the active binding site of the protein1KZN can frequently interact with targets. [ABSTRACT FROM AUTHOR]

A straightforward approach to synthesise isocoumarins via Rh(III)-catalyzed C–H/C–C bond activation/annulation cascade of enaminones and iodonium ylides has been explored. The established protocol is characterized by an exceedingly simple reaction system, high regioselectivity and good functional group tolerance. Moreover, this strategy may provide a new route to cleavage of the C(sp2)–C(O) bond of unstrained ketones. [ABSTRACT FROM AUTHOR]

Three new compounds including a meroterpenoid (1) and two isocoumarins (8 and 9), together with thirteen known compounds (2–7, 10–16) were isolated from the metabolites of Talaromyces amestolkiae MST1-15. Their structures were identified by a combination of spectroscopic analysis. The absolute configuration of compound 1 was elucidated on the basis of experimental and electronic circular dichroism calculation, and compounds 8 and 9 were determined by Mo2(OAc)4-induced circular dichroism experiments. Compounds 7–16 showed weak antibacterial activities against Stenotrophomonas maltophilia with MIC values ranging from 128 to 512 μg/mL (MICs of ceftriaxone sodium and levofloxacin were 128 and 0.25 μg/mL, respectively). [ABSTRACT FROM AUTHOR]

Isocoumarins, isomeric to comarins which act as effective carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, were investigated for the first time as inhibitors of this enzyme. A series of 3-substituted and 3,4-disubstituted isocoumarins incorporating phenylhydrazone, 1-phenyl-pyrazole and pyrazolo-substituted pyrimidine trione/thioxo-pyrimidine dione moieties were investigated for their interaction with four human (h) CA isoforms, hCA I, II, IX and XII, known to be important drug targets. hCA I and II were not inhibited by these compounds, whereas hCA IX and XII were inhibited in the low micromolar range by the less bulky derivatives. The inhibition constants ranged between 2.7-78.9 µM against hCA IX and of 1.2-66.5 µM against hCA XII. As for the coumarins, we hypothesise that the isocoumarins are hydrolysed by the esterase activity of the enzyme with formation of 2-carboxy-phenylacetic aldehydes which act as CA inhibitors. Isocoumarins represent a new class of CA inhibitors. [ABSTRACT FROM AUTHOR]

A novel Pd‐catalysed oxidative coupling between benzoic acids and vinylarenes or acrylates to furnish isocoumarins and phthalides is reported. The reaction proceeds smoothly in molten tetrabutylammonium acetate via a selective C−H bond activation, with very low percentage of ligand‐free palladium acetate as the catalyst, under atmospheric pressure of oxygen. Sub‐stoichiometric amount of copper acetate is also required as a reoxidant for the palladium. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the "Five Rules" of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value. [ABSTRACT FROM AUTHOR]

Various synthetic methodologies to obtain 3,4-diaminoisocumarin nucleus have been reported and described. However, mechanistic analysis based on experimental evidence is lacking. Herein, we report the synthesis of the novel 3-amino-4-(diphenylamino)-1H-2-benzopyran-1-one using a two-step methodology with a new mechanistic proposal to explain the formation of the latter based on previously reported precursors and the established conditions. This compound was afforded in 80% yield. [ABSTRACT FROM AUTHOR]

With the aim of obtaining derivatives belonging to 2′,3′-diphenyl-3H-spiro[[2]benzofuran-1,4′-imidazole]-3,5′(3′H)-dione nucleus, we synthesized 4-[(3-amino-1-oxo-1H-2-benzopyran-4-yl)amino]benzoic acid (a 3,4-diaminoisocoumarine derivative), a known precursor of 4-[(1-carbamoyl-3-oxo-1,3-dihydro-2-benzofuran-1-yl)amino]benzoic acid (a phthalide–carboxamide-bearing system) by a novel methodology that we report here. The reaction conditions were optimized to afford the latter in 62% yield. [ABSTRACT FROM AUTHOR]

The divergent synthesis of isobenzofuranones and isocoumarins was realized from the reaction of 2-alkenyl benzoic acids and mCPBA in the presence of catalytic aryl iodine and (±)-10-camphorsulfonic acid (CSA). The organocatalytic oxidative reaction is assumed to undergo a cascade process involving lactonization, 1,2-aryl migration and elimination enabled by a modified Koser reagent generated in situ. [ABSTRACT FROM AUTHOR]

Previously, different Hydrangea macrophylla ssp. serrata cultivars were investigated by untargeted LC-MS analysis. From this, a list of tentatively identified and unknown compounds that differ significantly between these cultivars was obtained. Due to the lack of reference compounds, especially for dihydro-isocoumarins, we aimed to isolate and structurally characterise these compounds from the cultivar 'Yae-no-amacha' using NMR and LC-MS methods. For purification and isolation, counter-current chromatography was used in combination with reversed-phase preparative HPLC as an orthogonal and enhanced purification workflow. Thirteen dihydro-isocoumarins in combination with other metabolites could be isolated and structurally identified. Particularly interesting was the clarification of dihydrostilbenoid glycosides, which were described for the first time in H. macrophylla ssp. serrata. These results will help us in further studies on the biological interpretation of our data. [ABSTRACT FROM AUTHOR]

A new copper catalysed desymmetrisation reaction of bisalkynyl ferrocenecarboxylic acids using (R,R)‐Ph‐Pybox results in the first asymmetric synthesis of planar chiral pseudo‐isocoumarins in up to 64 % enantiomeric excess and up to 99 % yield with complete regioselectivity. Tri‐functionalised planar chiral ferrocenes are synthesised in five steps from commercially available materials, without the need for traditional directing group chemistry via an easily diversified route exploiting the double Sonogashira coupling reaction. The absolute configuration of the chiral heterocycles is proven by chemical correlation and circular dichroism spectroscopy giving the asymmetric reaction synthetic utility and opening the way for the rational extension of this method to produce bioactive isocoumarin‐fused ferrocene derivatives. [ABSTRACT FROM AUTHOR]

An efficient catalytic system comprising of Pd2dba3/P(t-Bu)3H.BF4/Cy2NMe –for the Heck coupling in the synthesis of 3-alkenyl isochromen-1-ones, 3 has been developed. Air stable alkyl phosphonium salt, [(t-Bu)3Ph]BF4 was found to be vital for the activation of 3- chloroisochromen-1-ones, 1 in regio-selective Heck coupling reactions. The technique has additionally been reached out to typharin, penicilisorin and artemidin analogs. [ABSTRACT FROM AUTHOR]

Coriandrum sativum (coriander) is an edible herb in the family Apiaceae. The leaves, fruits, and stems of C. sativum have long been used as culinary spice due to their favorable odor. Traditional practitioners used this plant for treating different diseases like blepharitis, scabies, aphthous stomatitis, laryngitis, headache, and palpitation. In modern researches, coriander has demonstrated anxiolytic, anticonvulsant, antimigraine, neuroprotective, analgesic, diuretic, hypoglycemic, hypolipidemic, hypotensive, anticancer, and antioxidant activities. Coriander contains a wide range of bioactive phytochemicals among which phenylpropenes, terpenoids, isocoumarins, phytosterols, and fatty acids are the most important. This review provides information about the botanical and ethnobotanical aspects, chemical profile, therapeutic uses in Islamic traditional medicine (ITM), and recent pharmacological studies of coriander effects. The results have shown that coriander and its monoterpenoid compound, linalool, can be considered as potential drug candidates for treating metabolic syndrome and different inflammatory conditions especially neural and CNS diseases. [ABSTRACT FROM AUTHOR]

Clausena lenis Drake (C. lenis) is a folk medicinal herb to treat influenza, colds, bronchitis, and malaria. The 95% and 50% ethanol extract of C. lenis showed significant nitric oxide (NO) inhibition activity in BV-2 microglial cells stimulated by lipopolysaccharide (LPS). Bio-guided isolation of the active extract afforded five new compounds, including a chlorine-containing furoquinoline racemate, (±)-claulenine A (1), an amide alkaloid, claulenine B (2), a prenylated coumarin, claulenin A (3), a furocoumarin glucoside, clauleside A (4), and a multi-prenylated p-hydroxybenzaldehyde, claulenin B (5), along with 33 known ones. Their structures were determined via spectroscopic methods, and the absolute configurations of new compounds were assigned via the electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analysis. Compounds 2, 23, 27, 28, 33, and 34 showed potent anti-neuroinflammatory effects on LPS-induced NO production in BV-2 microglial cells, with IC50 values in the range of 17.6–40.9 μM. The possible mechanism was deduced to interact with iNOS through molecular docking. [ABSTRACT FROM AUTHOR]

Retraction of 'Ruthenium(II) CNN Pincer Complexes as Efficient Catalysts in Oxidative Annulation of Aromatic Acids with Alkynes to Isocoumarins' by Periasamy Viswanathamurthi et al., New J. Chem., 2023, https://doi.org/10.1039/D3NJ03745B. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oxidative carbonylation of 2-alkynylbenzoic acids and alkynylthiophencarboxylic acids. • Diverse carbonylation pathways followed by variously substituted substrates. • Structure of 11 products from different mechanistic pathways confirmed by XRD analysis. • Regioselective syntheses of isocoumarin and thienopyranone carboxylic esters. • Products formed in 54–91% isolated yields over more than 30 examples. The reactivity of 2-alkynylbenzoic acids under PdI 2 /KI-catalyzed oxidative alkoxycarbonylation conditions, with oxygen (from air) as external oxidant and an alcohol as external nucleophile, has been studied. It was found that substrates with triple bond substituted with a bulky alkyl group, such as tert -butyl, selectively underwent a 6- endo - dig cyclization - alkoxycarbonylation pathway with ethanol or isopropanol as nucleophile, to give high value added isocoumarin-4-carboxylic esters in good to high yields (67–87%). When applied to alkynylthiophencarboxylic acids bearing an internal triple bond, the reaction turned out to be completely regioselective toward the formation of the corresponding alkyl thienopyranonecarboxylates ensuing from 6- endo - dig cyclization-alkoxycarbonylation, regardless the nature of the substituent on the triple bond and the external alcohol (54–91% yields). To confirm the structure of the products deriving from different kinds of substrates, and therefore to corroborate the proposed mechanistic pathways, the crystalline structures of 11 new compounds have been resolved by XRD analysis. [ABSTRACT FROM AUTHOR]

Oxygen-containing heterocyclic 1H-isochromen-1-ones are core structural components of various natural products and biologically active compounds. They are used as functional substrates in the synthesis of biologically active 1H-isochromen-1-ones and isoquinolin-1(2H)-ones exhibiting different biological properties and diverse applications. Synthetic approaches to these classes of heterocyclic compounds developed in parallel from the very beginning because one of the strategies for the synthesis of isoquinolin-1-one is the recyclization of the isochromen-1-one system by the action of primary amines. In this review, we comprehensively describe the synthesis of 1H-isochromen-1-ones and isoquinolin-1(2H)-ones with a carbonyl function in position 3, summarize their use as synthons in organic chemistry and highlight their biological activities. [ABSTRACT FROM AUTHOR]

Natural products, remains the most important source for the discovery of new drugs for the treatment of human diseases. This has inspired the synthetic community to design and develop mimics of natural products either to answer important questions in biology or to explore their therapeutic potentials. Glycosides present themselves abundantly in nature, right from the cell surface receptors to natural products of any origin. The O‐Glycosides are hydrolytically less stable compared to C‐glycosides and this feature has presented a great opportunity for drug discovery. The discovery of Dapagliflozin, an SGLT inhibitor and C‐glucoside, for the treatment of diabetes is one such example. Aryl acyl‐anion chemistry has been explored for the synthesis of 2‐deoxy‐C‐aryl furanoside/pyranoside/septanosides. Besides success, the studies have provided valuable insight into the natural propensities of the architectural framework for the cascade to furan derivatives. The aryl acyl‐anion chemistry has also enabled the synthesis of biologically active diaryl heptanoids. Inspired from sucesss of Dapagliflozin, new analogues have been synthesized with pyridine and isocoumarin heterocycle as the proximal ring. C‐glucosides of isoliquiritigenin have been synthesized for the first time and evaluated as an efficient aldose reductase inhibitor. The synthesis and evaluation of acyl‐C‐β‐D‐glucosides and benzyl‐C‐β‐D‐glucoside as glucose‐uptake promoters has revealed promise in small molecules. The concept of building blocks has been used to obtain natural oxylipins, D‐xylo and L‐xylo‐configured alkane tetrols and novel lipophilic ketones with erythro/threo configured trihydroxy polar head‐group as possible anti‐mycobacterial agents. [ABSTRACT FROM AUTHOR]

In current decades, the fabrication and design of magnetic biocatalysts have been advancing as green catalysts. Hence, in this paper, we use the apple seed starch to create indium(III) immobilized on Fe 3 O 4 @apple seed starch core-shell magnetic nanocatalyst (Fe 3 O 4 @apple seed starch-In(III)). The prepared catalyst was identified and evaluated with several analysis techniques. The application of this catalyst in the synthesis of isochromeno[4,3- c ]pyrazole-5(1 H)-one derivates under solvent-free conditions was a new approach with high efficiency. Due to the magnetic nature of the catalyst, the catalyst separation from the reaction medium is easy, and it is reusable for five runs without significant change in catalytic activity. The fabrication of this catalyst is based on green chemistry principles and is more economical and stable than other catalysts in the synthesis of pyrazole-fused isocoumarins heterocyclic compounds. [Display omitted] • This study presents the Fe 3 O 4 @apple seed starch-In(III) fabrication and its application in the isochromeno[4,3- c ]pyrazole-5(1 H)-one derivates synthesis. • The heterogeneous catalyst is cost-effective, available, highly efficient, readily reusable, and separable. • The catalyst was characterized by FT-IR, FE-SEM, TEM, XRD, EDS, XPS, TGA, ICP-OES, VSM, and elemental mapping. [ABSTRACT FROM AUTHOR]

Efficient methods have been disclosed for the construction of nitrogen and oxygen containing heterocyclic systems attached to selenocysteine or selenoglutathione. An inorganic oxidant (K2S2O8) or a mild Lewis acid (CuBr2) was employed for the generation of selanyl electrophiles that were further trapped with phenyl propiolates, methyl 2-(phenylethynyl)benzoate, N-phenyl propiolamides and 2-(phenylethynyl)benzamide thus providing the respective coumarins, isocoumarins, quinolin-2-ones and isoquinolin-2-ones via 6-endo-dig cyclization. The use of visible light resulted in divergent reactivity providing triple bond addition products or spirocyclic compounds bearing selenocysteine moieties. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Divergent synthesis of useful skeletons has been realized via rhodium(III)‐catalyzed C—H activation of iminopyridinium ylides and coupling with various unsaturated coupling reagents. Isocoumarins and isoquinolones were obtained via cleavage of the C—N or N—N bond in the ylidic directing group, while fluorinated alkenes were delivered with the directing group intact. The reactions occurred with wide substrate scopes and good efficiency under redox‐neutral and air‐tolerant conditions. Representative products exhibit solid‐state fluorescent property and bioactivity of inhibition toward human cancer cells. [ABSTRACT FROM AUTHOR]

A new coumarin, angedahurin A (1), and seven known analogues (2-8), were isolated from the roots of Angelica dahurica. Their structures were identified by extensive NMR, IR, and HR-ESIMS spectroscopic analyses. The cytotoxicities of coumarins 1-8 against MG-63 human osteosarcoma cell lines were screened. Compound 1 showed significant cytotoxic effects against MG-63 with an IC50 value of 7.2 µM, for comparison, the positive control, 5-FU, had an IC50 value of 32.4 µM. Morphological features of apoptosis activities were evaluated in 1-induced MG-63 cells and the results confirmed MG-63 cell apoptosis in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

A silver salt‐mediated aerobic approach to access 4‐acetyl 3‐unsubstituted isocoumarins from the reaction of ortho‐iodobenzoic acid and enol ester in the presence of a base has been presented. The reaction proceeds through the base mediated initial cleavage of the enol ester followed silver‐mediated C‐arylation reaction. Intramolecular annulation of the resulting intermediate followed by dehydration produces the 4‐acyl isocoumarins. Selective demethylation of the 4‐acylated isocoumarin affords biologically potent AGI‐7, while selective reduction followed by demethylation enabled the sescandelin in good yield. [ABSTRACT FROM AUTHOR]

Two pairs of isocoumarin derivatives, (±)-rhytidhymarins A and B (1–2), one aromatic ester, rhytidhyster A (3), together with three known compounds (4–6) were isolated from fungus Rhytidhysteron sp. BZM-9. Compounds 1 and 2 are presented as racemates and resolved into optically pure enantiomers (+)-1/(−)-1 and (+)-2/(−)-2 by chiral column separation, respectively. Their planar structures were elucidated by HRESIMS, 1D and 2D NMR data and their absolute configurations were determined by X-ray crystallographic analysis and electronic circular dichroism (ECD) calculation. Compound 5 showed significant cytotoxic activity against SMMC7721 cells with an IC50 value of 0.338 μM and exhibited moderate antimicrobial activity to MRSA with a MIC value of 6.25 μg mL−1; compound 3 showed cytotoxicity against HepG2 cells with an IC50 value of 11.46 μM. [ABSTRACT FROM AUTHOR]

In the continuation of our study of substituted isocoumarins a series of novel 3-azolyl isocoumarin and their thio derivatives, including some related lactone compounds was prepared and biologically profiled against C. albicans showing moderate activity with MIC values in range of 4-60 μg mL-1, in general. The additional characterisation of selected compounds was carried out by exploring their activity on CYP3A4 and CYP2D6 enzymes, while experiments on mutagenicity were performed by AMES test. The representative isocoumarins 3b, 4a and 4b showed lower inhibitory activity on CYP enzymes, when compared to the reference inhibitors, ketoconazole and quinidine. Compound 4a showed a higher mutagenic potential than the other two compounds. Further characterization included cytotoxicity profiling against normal MRC5 cells. [ABSTRACT FROM AUTHOR]