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Dearomative functionalization of heteroarenes offers an attractive and sustainable approach for the rapid construction of complex 3D heterocyclic scaffolds from planar structures. Despite progress in this field, dearomative amination of heteroarenes via a radical anion intermediate remains a challenge. Here, we report a photoredox-catalyzed dearomative hydroamination of heteroarenes with hydrazodiformates under mild and transition-metal-free reaction conditions. Various benzofurans and benzothiophenes can efficiently participate in this transformation. A series of mechanistic experiments revealed that heteroaryl radical anions are the crucial intermediates, generated through photo-induced electron transfer between the excited phenolate photocatalyst and heteroarenes. [ABSTRACT FROM AUTHOR]

Benzoheteroles are promising structural scaffolds in the realm of medicinal chemistry, but sustainable synthesis of 2,3‐difunctionalized benzoheterole derivatives is still in high demand. Indeed, we have conceptually rationalized the intrinsic reactivity of propargylic‐enyne systems for the flexible construction of 2,3‐disubstituted benzoheteroles through radical sulfonylative‐cyclization cascade under organophotoredox catalysis. We hereby report an efficient visible‐light‐induced sulfonyl radical‐triggered cyclization of 1,6‐enynols with sulfinic acids under the dual catalytic influence of 4CzIPN and NiBr2⋅DME, which led to the formation of 2,3‐disubstituted benzoheteroles in good to high yields. Additionally, the Rose Bengal (RB)‐catalyzed radical sulfonylative‐cycloannulation of acetyl‐derived 1,6‐enynols with sulfinic acids under blue LED irradiation allowed to access 3‐(E‐styryl)‐derived benzofurans and benzothiophenes in moderate to good yields. The scope and limitations of the present strategies were successfully established using different classes of 1,6‐enynols and sulfinic acids bearing various sensitive functional groups, yielding the desired products in a highly stereoselective fashion. Plausible mechanistic pathways were also proposed based on the current experimental and control experiments. [ABSTRACT FROM AUTHOR]

Various indoles undergo Friedel–Crafts alkylation at the 3-position when treated with secondary arylmethyl acetates in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine. Tertiary benzylic alcohols are also effective alkylating agents, undergoing TMSOTf-promoted activation to yield alkylated indoles that feature quaternary centers. A related study shows that benzofuran reacts under similar conditions to yield 2-alkylated benzofurans when treated with similar alkylating agents, and the reaction has been extended to include other representative heteroarenes. Yields for these Friedel–Crafts alkylation products range from 43%–99% over a wide range of substrate combinations. [ABSTRACT FROM AUTHOR]

Hydrazine, a compound known for its toxicity to human health and the environment, finds extensive use across various industries and potentially contributes to several diseases. Hence, the accurate measurement of hydrazine levels is paramount. This study introduces three new aggregation induced emissive luminogens (AIEgens) GBY-7, GBY-8, and GBY-9 crafted from benzofuran infused with a dicyanovinylidene group, tailored specifically for hydrazine monitoring. These probes feature a D–π–A core with a rotor, providing an optimal fluorescent base. Additionally, a potent electron-attracting nitrile group aids in the nucleophilic addition of N2H4 to form hydrazone, thereby blocking the intramolecular charge transfer (ICT) process and inducing optical signal modulation. Notably, luminogens GBY-8 and GBY-9 exhibit high selectivity in detecting hydrazine amidst competing amine-based compounds, showing detection limits of 0.00020 mM and 0.0043 mM, respectively. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed cascade cyclization and alkynylation of 2‐alkynylphenols with bromoalkynes to the synthesis of 3‐alkynylbenzofuran scaffolds has been developed. A variety of 3‐alkynylbenzofuran derivatives were prepared in good yields under mild conditions. Notably, this protocol was applied to the late‐stage modification of bioactive molecule. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chemodivergent synthesis of benzofurans and 2,3‐dihydrobenzofurans has been realized. Under a reaction system consisting of DBDMH and K2CO3 as promotors, controlled conditions enabled the formation of two sets of valuable heterocycles from the tandem transformation of enaminones and salicylaldehydes. The key to success was the identification of the reaction parameters, in which the imine intermediate which was formed by transient halogenation coupling and substitution processes underwent either aldol condensation/annulation or imine hydrolysis/aldol condensation. The additives NH4Cl or Fe2(SO4)3 controlled the unique selectivity of this reaction. A broad substrate scope of enaminones and salicylaldehydes has been employed in this reaction, demonstrating excellent functional group tolerance and versatility. [ABSTRACT FROM AUTHOR]

A class of novel chiral‐bridged biphenyl monophosphine ligands with a benzofuran moiety (He‐phos) has been successfully synthesized and reported. These ligands exhibited good performance in the gold‐catalyzed enantioselective cycloaddition reaction of 2‐(1‐alkynyl)‐2‐en‐1‐ones with nitrones, resulting in the successful preparation of a series of polyaryl‐substituted heterocyclic compounds with high enantioselectivities (up to 99% yield, 98% ee). The wide substrate adaptability (53 examples) and mild reaction conditions demonstrate the practicability of He‐phos in this reaction. [ABSTRACT FROM AUTHOR]

N,N‐dialkylbenzofuran‐ and N,N‐dialkylbenzothiophene‐2‐carboxamides were readily prepared from bare benzofuran and benzothiophene by deprotocupration followed by trapping with N,N‐dialkylcarbamoyl chlorides. They were reacted with 2‐benzofuryl‐ and 2‐benzothienyllithiums to form symmetrical and unsymmetrical diarylketones, or underwent deprotolithiation‐electrophilic trapping sequences at their 3 position. From 3‐iodinated derivatives, copper‐catalysed N‐arylation of azoles was performed, followed by lithium amide‐promoted cyclisation, to give 'tripentone' analogues. The diarylketones were also iodinated at their 3,3' positions and then engaged in the copper‐promoted double N‐arylation of anilines, giving rise to a family of original pentacyclic derivatives. A preliminary assessment of their electrochemical and biological properties was carried out, showing promising results against the proliferation of melanoma cells. [ABSTRACT FROM AUTHOR]

We describe herein the additive‐controlled divergent [4+2] cycloaddition and 1,4‐Michael addition reaction of benzofuran‐derived azadienes (BDAs) with enamides. An unprecedented [4+2] cycloaddition reaction of BDAs and enamide compounds was developed in the presence of 4 Å MS, providing a variety of structurally complex decahydrobenzofuro[3,2‐b]quinolines (13 examples) in moderate to excellent yields (59–98 % yields) with single diastereoisomer obtained. While employing MgSO4 as desiccant, the chemoselectivity was switched to the 1,4‐addition reactions, leading to a wide range of highly functionalized hybrids of benzofurans and enamide compounds (25 examples) in 25–94 % yields under mild conditions. [ABSTRACT FROM AUTHOR]

In this study, our primary objective was to synthesize and characterize a copper nanoparticle-modified oxidized graphite carbon nitride (ox-g-C3N4). This modified ox-g-C3N4 material was utilized as a reusable catalyst for the environmentally friendly production of benzofuran 4(a-j) derivatives through C–H activation using an electrochemical oxidation system. The desired derivatives were obtained by reacting 2-bromophenol 1(a-c) with ethynylbenzene 2(a-g) yielding high yields ranging from 89 to 94%. The modified Cu/ox-g-C3N4 nanocomposite was thoroughly examined. using different analytical techniques, including thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), IR Fourier-transform infrared spectroscopy (FT-IR), Brunauer–Emmett–Teller (BET) analysis, cyclic voltammetry (CV), and X-ray diffraction (XRD) spectroscopy, and ultraviolet (UV) spectroscopy. The comprehensive identification was conducted in a comparative manner, allowing for a thorough understanding of the nanocomposite's properties. By employing this nanocatalyst, we implement a greener synthesis approach that reduces the need for dangerous and toxic substances, while reducing waste generation by promoting reuse. The synthesized products in this research were subjected to characterization utilizing techniques such as melting point analysis, CHN analysis and 1HNMR spectroscopy. These analytical methods were utilized to confirm the identification and assess the purity of the benzofuran compounds synthesized 4(a-j). [ABSTRACT FROM AUTHOR]

The Stimulator of Interferon Genes (STING) is involved in cytosolic DNA sensing and type I Interferons (IFN-I) induction. Aiming to identify new STING agonists with antiviral activity and given the known biological activity of benzothiazole and benzimidazole derivatives, a series of benzofuran derivatives were tested for their ability to act as STING agonists, induce IFN-I and inhibit viral replication. Compounds were firstly evaluated in a gene reporter assay measuring luciferase activity driven by the human IFN-β promoter in cells expressing exogenous STING (HEK293T). Seven of them were able to induce IFN-β transcription while no induction of the IFN promoter was observed in the presence of a mutated and inactive STING, showing specific protein-ligand interaction. Docking studies were performed to predict their putative binding mode. The best hit compounds were then tested on human coronavirus 229E replication in BEAS-2B and MRC-5 cells and three derivatives showed EC50 values in the μM range. Such compounds were also tested on SARS-CoV-2 replication in BEAS-2B cells and in Calu-3 showing they can inhibit SARS-CoV-2 replication at nanomolar concentrations. To further confirm their IFN-dependent antiviral activity, compounds were tested to verify their effect on phospho-IRF3 nuclear localization, that was found to be induced by benzofuran derivatives, and SARS-CoV-2 replication in Vero E6 cells, lacking IFN production, founding them to be inactive. In conclusion, we identified benzofurans as STING-dependent immunostimulatory compounds and host-targeting inhibitors of coronaviruses representing a novel chemical scaffold for the development of broad-spectrum antivirals.

AbstractThe phytochemical investigation of the methanol extract of the seeds of Magydaris pastinacea afforded two undescribed benzofuran glycosides, furomagydarins A-B (1, 2), together with three known coumarins. The structures of the new isolates were elucidated after extensive 1D and 2D NMR experiments as well as HR MS. Compound 1 was able to inhibit the COX-2 expression in RAW264.7 macrophages exposed to lipopolysaccharide, a pro-inflammatory stimulus. RT-qPCR and luciferase reporter assays suggested that compound 1 reduces COX-2 expression at the transcriptional level. Further studies highlighted the capability of compound 1 to suppress the LPS-induced p38MAPK, JNK, and C/EBPβ phosphorylation, leading to COX-2 down-regulation in RAW264.7 macrophages.

Over past few decades, synthetic chemists are working tirelessly for the development of environmentally benign and economically competent carbon‐oxygen bond formation processes. Various oxidizing reagents and catalysts are being used to serve this purpose. Among all, t‐butyl hydrogen peroxide (TBHP) has emerged as a greener and economically viable oxygen source, radical initiator and precursor of t‐BuO⋅ and t‐BuOO⋅ radicals. It has been extensively utilized as a reagent for the synthesis of epoxides, ketones, secondary alcohols, heterocyclic rings like benzofurans, isoquinoline and many more. The present review will unfold the recent advancements made in the field of TBHP‐promoted C−O bond formation. [ABSTRACT FROM AUTHOR]

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G‐PN column containing 2,6‐di‐O‐pentyl‐3‐propionyl‐γ‐cyclodextrin and a Lipodex™ D column containing heptakis‐(2,6‐di‐O‐pentyl‐O‐acetyl)‐β‐cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS‐QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA‐derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G‐PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively. [ABSTRACT FROM AUTHOR]

An unusual benzofuran synthesis from 2,6-disubstituted phenols and alkynyl sulfoxides is disclosed. Various highly substituted benzofurans were synthesized via the charge-accelerated [3,3]-sigmatropic rearrangement and subsequent substituent migration. Multiaryl-substituted benzofurans and fully substituted benzofurans were prepared on the basis of the unique reaction mechanism. [ABSTRACT FROM AUTHOR]

Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons. [ABSTRACT FROM AUTHOR]

Chemical exploration of the total extract derived from Epicoccum nigrum Ann-B-2, an endophyte associated with Annona squamosa fruits, afforded two new metabolites, epicoccofuran A (1) and flavimycin C (2), along with four known compounds namely, epicocconigrone A (3), epicoccolide B (4), epicoccone (5) and 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (6). Structures of the isolated compounds were elucidated using extensive 1D and 2D NMR along with HR-ESI–MS. Flavimycin C (2) was isolated as an epimeric mixture of its two diastereomers 2a and 2b. The new compounds 1 and 2 displayed moderate activity against B. subtilis, whereas compounds (2, 3, 5, and 6) showed significant antiproliferative effects against a panel of seven different cancer cell lines with IC50 values ranging from 1.3 to 12 µM. [ABSTRACT FROM AUTHOR]

A set of nine derivatives, including five brominated compounds, was synthesized and the structures of these novel compounds were confirmed using 1H and 13C NMR as well as ESI MS spectra. These compounds were tested on four different cancer cell lines, chronic myelogenous leukemia (K562), prostate cancer (PC3), colon cancer (SW620), human kidney cancer (Caki 1), and on healthy human keratocytes (HaCaT). MTT results reveal that two newly developed derivatives (6 and 8) exhibit selective action towards K562 cells and no toxic effect in HaCat cells. The biological activity of these two most promising compounds was evaluated by trypan blue assay, reactive oxygen species generation, and IL-6 secretion. To investigate the proapoptotic activity of selected compounds, the two following types of tests were performed: Annexin V Apoptosis Detection Kit I and Caspase-Glo 3/7 assay. The studies of the mechanism showed that both compounds have pro-oxidative effects and increase reactive oxygen species in cancer cells, especially at 12 h incubation. Through the Caspase-Glo 3/7 assay, the proapoptotic properties of both compounds were confirmed. The Annexin V-FITC test revealed that compounds 6 and 8 induce apoptosis in K562 cells. Both compounds inhibit the release of proinflammatory interleukin 6 (IL-6) in K562 cells. Additionally, all compounds were screened for their antibacterial activities using standard and clinical strains. Within the studied group, compound 7 showed moderate activity towards Gram-positive strains in antimicrobial studies, with MIC values ranging from 16 to 64 µg/mL. [ABSTRACT FROM AUTHOR]

Objective: Benzofurans, fused pyrazole systems, and thiazole moieties are the most important pharmacophores and intermediates for making drugs. The preparation and anti-cancer activity of novel benzofuran-pyrazole-containing amino thiazole hybrids. Methods: The synthesized benzofuran-pyrazole containing amino thiazole hybrids (VIIa–VIIi). The anticancer activity of (VIIa–VIIi) against MCF-7, and A549 cell lines was determined using the MTT-assay, and also screened with in silico molecular docking studies. Results: The most potent compounds (E)-2-(2-((3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-4-(4-chlorophenyl)thiazole (VIIg) and (E)-2-(2-((3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-4-(p-tolyl)thiazole (VIIb) exhibited excellent anticancer activity against the MCF-7 and A549 cancer cell lines. Additionally, the synthesis hybrids and Erlotinib were screened for their in silico molecular docking studies against the EGFR (4HJO) receptor. The compounds (VIIg) and (VIIb) exhibited significantly higher binding scores and inhibitory constants than the reference drug Erlotinib. Conclusions: It has been observed that the substitution on the 4-chloro phenyl ring (VIIg) and 4-methyl phenyl ring (VIIb) important for maintaining their anticancer activity. The outcomes of the kinase inhibitory assay of these significant (VIIg) and (VIIb) hybrids against the tyrosine kinase EGFR strongly corroborated the in vitro anticancer findings and the in silico docking investigations. This research showed that newly developed compounds have potential as anticancer agents and suggested leads for further research. [ABSTRACT FROM AUTHOR]

The essential aim of the present study is designed to utilize 4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbonitrile (1) to build some novel heterocyclic systems containing benzofurans as well as furo[3,2-g]chromenes. Ring opening ring closure reactions of compound 1 with N-phenyl-2-cyanoacetamide produced 8-amino-furochromenopyridine-7-carboxamide 2, which cyclized with some electrophilic reagents giving furochromenopyridopyrimidines (63–73% yields). The reaction of carbonitrile 1 with pyrazolone derivatives yielded furochromenopyrazolopyridines 10 and 11 in good yields. Also, benzo[h]furochromeno naphthyridine 13 was synthesized from recyclization of carbonitrile 1 with 1-ethyl-4-hydroxyquinolin-2(1H)-one (12). On a different mechanism, recyclization of carbonitrile 1 with some 1,3-binucleophiles afforded pyrido[2,3-d]pyrimidines (14 and 15), pyrimido[1,2-a]pyrimidine 17 and pyrimido[2,1-c][1,2,4]triazine 19 in suitable yields (62–71%). Finally, the reaction of carbonitrile 1 with 1,3-cyclohexanedione and 1,4-cyclohexanedione in 2:1 molar ratio yielded polyfused systems 20 and 21, respectively. Based on spectral and analytical results, the structures of the all products were inferred. [ABSTRACT FROM AUTHOR]

Several fluorine-18-labeled PET β-amyloid (Aβ) plaque radiotracers for Alzheimer’s disease (AD) are in clinical use. However, no radioiodinated imaging agent for Aβ plaques has been successfully moved forward for either single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Radioiodinated pyridyl benzofuran derivatives for the SPECT imaging of Aβ plaques using iodine-123 and iodine-125 are being pursued. In this study, we assess the iodine-124 radioiodinated pyridyl benzofuran derivative 5-(5-[124I]iodobenzofuran-2-yl)-N,N-dimethylpyridin-2-amine ([124I]IBETA) (Ki = 2.36 nM) for utilization in PET imaging for Aβ plaques. We report our findings on the radioiododestannylation reaction used to prepare [124/125I]IBETA and evaluate its binding to Aβ plaques in a 5 × FAD mouse model and postmortem human AD brain. Both [125I]IBETA and [124I]IBETA are produced in >25% radiochemical yield and >85% radiochemical purity. The in vitro binding of [125I]IBETA and [124I]IBETA in transgenic 5 × FAD mouse model for Aβ plaques was high in the frontal cortex, anterior cingulate, thalamus, and hippocampus, which are regions of high Aβ accumulation, with very little binding in the cerebellum (ratio of brain regions to cerebellum was >5). The in vitro binding of [125I]IBETA and [124I]IBETA in postmortem human AD brains was higher in gray matter containing Aβ plaques compared to white matter (ratio of gray to white matter was >5). Anti-Aβ immunostaining strongly correlated with [124/125I]IBETA regional binding in both the 5 × FAD mouse and postmortem AD human brains. The binding of [124/125I]IBETA in 5 × FAD mouse and postmortem human AD brains was displaced by the known Aβ plaque imaging agent, Flotaza. Preliminary PET/CT studies of [124I]IBETA in the 5 × FAD mouse model suggested [124I]IBETA was relatively stable in vivo with a greater localization of [124I]IBETA in the brain regions with a high concentration of Aβ plaques. Some deiodination was observed at later time points. Therefore, [124I]IBETA may potentially be a useful PET radioligand for Aβ plaques in brain studies.

Notably, substrates B 1s b and B 1t b bearing a heteroaryl group and a naphthyl group, respectively, also served as suitable reaction partners, participating in the formal (2+1) cycloaddition to provide the benzofuranone-based spirocyclopropanes B 3sa b and B 3ta b , respectively (entries 19 and 20). [15][16][24][32][33] As shown in Scheme 1a, benzofuran-derived oxadienes are widely used as two-atom building blocks in highly diastereoselective (2+3) cycloadditions. Moreover, I ortho i -, I meta i - and I para i -substituted phenyl groups were found to be suitable R SP 1 sp groups for the benzofuran-derived oxadienes B 1 b , affording the target products B 3fa b - B ra b in overall high yields and moderate to good diastereoselectivities (entries 6-18). Keywords: (2+1) cycloaddition; diastereoselectivity; benzofurans; oxadienes; bromomalonates; spiro compounds EN (2+1) cycloaddition diastereoselectivity benzofurans oxadienes bromomalonates spiro compounds 1704 1708 5 08/18/23 20230901 NES 230901 Graph Benzofuran is an important class of oxygen-containing heterocycles that frequently occur as substructures in natural products and synthetic compounds. [Extracted from the article]

The importance of the benzo[b]furan motif becomes evident in the remarkable results of numerous biological investigations, establishing its potential as a robust therapeutic option. This review presents an overview of the synthesis of and exhaustive biological studies conducted on benzo[b]furan derivatives from 2011 to 2022, accentuating their exceptional promise as anticancer, antibacterial, and antifungal agents. Initially, the discussion focuses on chemical synthesis, molecular docking simulations, and both in vitro and in vivo studies. Additionally, we provide an analysis of the intricate interplay between structure and activity, thereby facilitating comparisons and profoundly emphasizing the applications of the benzo[b]furan motif within the realms of drug discovery and medicinal chemistry. [ABSTRACT FROM AUTHOR]

The translation inhibitor rocaglamide A (RocA) has shown promising antitumor activity because it uniquely clamps eukaryotic initiation factor (eIF) 4A onto polypurine RNA for selective translational repression. As eIF4A has been speculated to be a unique target of RocA, alternative targets have not been investigated. Here, we reveal that DDX3 is another molecular target of RocA. Proximity-specific fluorescence labeling of an O-nitrobenzoxadiazole-conjugated derivative revealed that RocA binds to DDX3. RocA clamps the DDX3 protein onto polypurine RNA in an ATP-independent manner. Analysis of a de novo-assembled transcriptome from the plant Aglaia, a natural source of RocA, uncovered the amino acid critical for RocA binding. Moreover, ribosome profiling showed that because of the dominant-negative effect of RocA, high expression of eIF4A and DDX3 strengthens translational repression in cancer cells. This study indicates that sequence-selective clamping of DDX3 and eIF4A, and subsequent dominant-negative translational repression by RocA determine its tumor toxicity.

Herein, a concise method for the Rh(III)-catalyzed, directing-group-assisted C–H/C–H cross-coupling of N-heterocycles (quinolines, indolines, indoles, pyridines, pyrimidines, pyrazoles) with other heteroarenes (benzoxazoles, benzofurans, and thiophenes) is disclosed for the synthesis of unsymmetrical heterobiaryl compounds in good to excellent yields. A plausible catalytic cycle has been delineated based on experimental and computational mechanistic studies. [ABSTRACT FROM AUTHOR]

Tuberculosis is an infectious disease that has re-emerged in multiple/extensively resistant forms (MDR/XDR) since 1990's creating threat to the mankind. The marketed drugs are not fully effective on these forms as they suffer from serious side effects. Thus developing drugs targeting the novel targets is the need of the hour to treat the disease. Many novel targets have been identified and Polyketide synthase 13 (Pks 13) has emerged as one of the promising targets to treat the tuberculosis. It links the meromycolic acid (C48-C64) branch originating from FAS-II, and α -alkyl C26 fatty acid branch originating from fatty acid synthase I (FAS-I) via Claisen condensation and helps in final formation of precursors of mycolic acid, the major component of Cell walls of M. tuberculosis. It has five domains viz Acyl Carrier Protein -Keto acyl Synthase-Acetyl Tranferase-Acyl Carrier Protein-Thioesterase [ACP-KS-AT-ACP-TE]. The ACP domain has two portions and one of them is adjacent to KS domain (N- terminal ACP) and C-terminal ACP resides beside of TE domain. The N-ACP domain and TE domains have active sites. Thus, efforts are made to design, synthesize and test the Novel Chemical Entities (NCE's) for their antitubercular activity with Pks 13 enzyme as a target. The benzofurans, thiophenes, coumestans and β lactones have been identified as ligands blocking Pks 13 enzyme with promising antitubercular activity. This article summarizes these classes of Pks 13 enzyme inhibitors exhibiting potential antitubercular activity along with their limitations and discusses the future scope. [ABSTRACT FROM AUTHOR]

Herein, the tandem synthesis of various CF3Se‐containing heterocyclic compounds has been developed, using Tf2O as the catalyst and trifluoromethyl selenoxides as the electrophilic trifluoromethylselenolation reagents. This process is characterized by its mild conditions, ease of operation, and good functional group compatibility. A variety of alkynes could be transferred into CF3Se‐containing indoles, benzofurans, benzothiophenes, isoquinolines and chromenes in good yields. A key step involving the formation of the electrophilic CF3Se species was proposed. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chemical functionalization of fullerenes has been an important topic in fullerene chemistry. Herein, an unprecedented Pd‐catalyzed migration reaction of [60]fullerene with allyloxy‐tethered aryl iodides is present for the preparation of novel [60]fullerene‐fused allylbenzofurans. The use of 1,2‐bis(diphenylphosphino)benzene (DPPBz) as a ligand is crucial for the success of the transformation. The reaction shows high chemo‐ and regioselectivity, and is flexible with regard to allyl‐migration site, providing a new and efficient approach to rare [60]fullerene‐fused benzofurans. Control experiments disclose that the reaction most probably undergoes a sequential C—O bond cleavage/allyl‐migration/intermolecular cycloaddition cascade process. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chemical functionalization of fullerenes has been an important topic in fullerene chemistry. Herein, an unprecedented Pd‐catalyzed migration reaction of [60]fullerene with allyloxy‐tethered aryl iodides is present for the preparation of novel [60]fullerene‐fused allylbenzofurans. The use of 1,2‐bis(diphenylphosphino)benzene (DPPBz) as a ligand is crucial for the success of the transformation. The reaction shows high chemo‐ and regioselectivity, and is flexible with regard to allyl‐migration site, providing a new and efficient approach to rare [60]fullerene‐fused benzofurans. Control experiments disclose that the reaction most probably undergoes a sequential C—O bond cleavage/allyl‐migration/intermolecular cycloaddition cascade process. [ABSTRACT FROM AUTHOR]

Isocyanides bearing electron-donating groups (R = OMe, Me) and halogen group (R = Cl) on the phenyl ring performed well to give moderate to good yields of the corresponding benzofurans B 3p b - B r b . 2,6-Dimethylphenyl isocyanide also proceeded well ( B 3s b ). Keywords: Lewis acid; [4+1] cycloaddition; o -quinone methides; isocyanides; benzofurans EN Lewis acid [4+1] cycloaddition o -quinone methides isocyanides benzofurans 1230 1234 5 06/19/23 20230704 NES 230704 Benzofuran is a privileged structural unit of many pharmaceutical molecules [1][2] and various natural products. Lewis acid, [4+1] cycloaddition, isocyanides, benzofurans, o -quinone methides. [Extracted from the article]

Benzofuran and 2,3-dihydrobenzofuran scaffolds are heterocycles of high value in medicinal chemistry and drug synthesis. Targeting inflammation in cancer associated with chronic inflammation is a promising therapy. In the present study, we investigated the anti-inflammatory effects of fluorinated benzofuran and dihydrobenzofuran derivatives in macrophages and in the air pouch model of inflammation, as well as their anticancer effects in the human colorectal adenocarcinoma cell line HCT116. Six of the nine compounds suppressed lipopolysaccharide-stimulated inflammation by inhibiting the expression of cyclooxygenase-2 and nitric oxide synthase 2 and decreased the secretion of the tested inflammatory mediators. Their IC50 values ranged from 1.2 to 9.04 µM for interleukin-6; from 1.5 to 19.3 µM for Chemokine (C-C) Ligand 2; from 2.4 to 5.2 µM for nitric oxide; and from 1.1 to 20.5 µM for prostaglandin E2. Three novel synthesized benzofuran compounds significantly inhibited cyclooxygenase activity. Most of these compounds showed anti-inflammatory effects in the zymosan-induced air pouch model. Because inflammation may lead to tumorigenesis, we tested the effects of these compounds on the proliferation and apoptosis of HCT116. Two compounds with difluorine, bromine, and ester or carboxylic acid groups inhibited the proliferation by approximately 70%. Inhibition of the expression of the antiapoptotic protein Bcl-2 and concentration-dependent cleavage of PARP-1, as well as DNA fragmentation by approximately 80%, were described. Analysis of the structure–activity relationship suggested that the biological effects of benzofuran derivatives are enhanced in the presence of fluorine, bromine, hydroxyl, and/or carboxyl groups. In conclusion, the designed fluorinated benzofuran and dihydrobenzofuran derivatives are efficient anti-inflammatory agents, with a promising anticancer effect and a combinatory treatment in inflammation and tumorigenesis in cancer microenvironments. [ABSTRACT FROM AUTHOR]

Substituted pyridines with diverse functional groups are important structural motifs found in numerous bioactive molecules. Several methodologies for the introduction of various bio-relevant functional groups to pyridine have been reported, but there is still a need for a single robust method allowing the selective introduction of multiple functional groups. This study reports a ring cleavage methodology reaction for the synthesis of 2-alkyl/aryl 3-electron-withdrawing groups (esters, sulfones, and phosphonates) 5-aminoaryl/phenol pyridines via the remodeling of 3-formyl (aza)indoles/benzofurans. Totally ninety-three 5-aminoaryl pyridines and thirty-three 5-phenol pyridines were synthesized showing the robustness of the developed methodology. The application of this methodology further provided a privileged pyridine scaffold containing biologically relevant molecules and direct drug/natural product conjugation with ethyl 2-methyl nicotinate. Substituted pyridines are important structural motifs present in various bioactive molecules, however their multi-functionalization remains challenging. Here, the authors report a facile approach for introducing various functional groups on the pyridine scaffold by remodeling of 3-formyl (aza)indoles/benzofurans via a ring cleavage reaction. [ABSTRACT FROM AUTHOR]

5-(2-Aminopropyl)benzofuran (5-APB), also known as "Benzo Fury," is a novel psychoactive substance (NPS) belonging to a new class of synthetic phenethylamines. It acts by disrupting serotonergic circuits as a serotonin–norepinephrine–dopamine reuptake inhibitor and is classified as an entactogen, similar to MDMA and MDA. Despite its popularity among users, recent toxicity events have been associated with the consumption of 5-APB and other benzofurans, highlighting the need for a better understanding of their pharmacodynamics and toxicity. One way to achieve this is by developing the synthesis of 5-APB metabolites as biomarkers of exposure. In this study, we present a six-step synthesis for one of the 5-APB metabolites, 2-(5-(2-aminopropyl)-2-hydroxyphenyl)acetic acid (1), involving methylation, formylation, Aldol-type condensation, reduction, and hydrolysis reactions. The compound was obtained in an overall yield of 11%. [ABSTRACT FROM AUTHOR]

Herein, an efficient lithium tert‐butoxide/DMSO‐mediated rapid synthesis of naphthalenes, benzofurans, and indoles is reported. The anticipated aromatics and heteroaromatics are obtained in high yields within a few minutes, even in a decagram‐scale reaction. [ABSTRACT FROM AUTHOR]

Background and aimsThe advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' cohort of patients with CKD.MethodsWe performed an observational single-arm multi-centre study in a large (n=198) cohort of patients with stage 1-3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA

A new benzofuran, Cochinfuran A (1), and four known benzofurans (2-5) were isolated from the heartwood of Dalbergia cochinchinensis Pierre ex Laness. The chemical structure of the new benzofuran was determined based on broad NMR and mass spectrometry evaluation. Bioactivity assays showed that the compounds 1-3 and 5 were found as anti-inflammatory agents with IC50 values 49.01 ± 1.54, 1368.93 ± 0.98, 67.48 ± 0.92 and 77.91 ± 1.53 µM, respectively. They could reduce the production of NO (P<0.001) with 3.52~7.04, 1.96~7.84, 1.85~7.40 and 0.98~3.93 µM and restrained LDH (P<0.01) with 3.52~7.04, 3.93~7.84, 3.70~7.40 and 0.98~3.93 µM in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, respectively, the compound 4 (IC50 218.20 ± 3.39 µM) showed no anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

The review summarizes the existing methods for the synthesis of 2-nitrobenzofurans and their polycondensed derivatives, which present valuable substrates for effecting dearomatization of the furan ring. Electrophilic nitration of 2-unsubstituted benzofurans, ipso substitution, condensation of salicylic aldehydes with bromonitromethane, and oxidation of 2-(2-nitroethyl)phenols have received the most attention. [ABSTRACT FROM AUTHOR]

N‐(Anisyl)‐5‐(2‐chloroacetamido)‐4‐cyano‐3‐methylthiophene‐2‐carboxamide (3) was synthesized and reacted with several nucleophilic reagents. The reactions with sulfur nucleophiles (namely, mercaptoacetic acid, ethyl 2‐mercaptoacetate, 5‐(phenylamino)‐1,3,4‐thiadiazole‐2‐thiol, 2‐mercapto‐4,6‐dimethyl‐nicotinonitrile, 4‐anilino‐3‐arylazo‐4‐mercapto‐butenones, ethyl 3‐anilino‐2‐arylazo‐3‐mercapto‐acrylates, and ammonium thiocyanate) yielded the corresponding sulfide, thiophene, or thiazolin‐4‐one derivatives, respectively. The reaction with salicylaldehyde (an example of oxygen nucleophile) furnished the targeting benzofuran compound 21. The reactions with nitrogen nucleophiles (namely, piperidine and aniline) yielded the corresponding thiophene‐carboxamide derivatives 23 and 25, respectively. IR, 1H NMR, and 13C NMR were used to deduce the structures of the target thiophene containing compounds. The effect of the synthesized thiophenes on the viability of HepG2, A2780, and A2780CP was determined. The most effective drug was shown by the thienopyridine‐carboxamide compound 11, against liver cancer cell lines (HepG2) and ovarian cancer cell lines (A2780CP and A2780), whose IC50 values were remarkably near those of Sorafenib, the antitumor drug. [ABSTRACT FROM AUTHOR]

A novel heavy metal‐free and safe synthetic methodology enabling one‐step conversion of ketones into corresponding 4,5,6,7‐tetrafluorobenzofurans (F4BFs) has been developed. The presented approach has numerous advantageous qualities, including utilization of readily available substrates, broad scope, scalability, and good reaction yields. Importantly, some of the benzofurans prepared by this method were heretofore inaccessible by any other known transformation. Importantly, furo[2,3‐b]pyrazines and heretofore unexplored difuro[2,3‐c:3′,2′‐e]pyridazine can be prepared using this strategy. Spectroscopic studies reveal that for simple systems, absorption and fluorescence maxima fall within the UV spectral range, while π‐electron system expansion red‐shifts both spectra. Moreover, the good fluorescence quantum yields observed in solution, up to 96 %, are also maintained in the solid state. Experimental results are supported by density functional theory (DFT) calculations. The presented methodology, combined with the spectroscopic characteristics, suggest the possibility of using F4BFs in the optoelectronic industry (i. e., organic light emitting devices (OLED), organic field‐effect transistors (OFET), organic photovoltaics (OPV)) as inexpensive and readily available emissive or semiconductor materials. [ABSTRACT FROM AUTHOR]

The synthetic methods of 2,3‐disubstituted benzofurans have been widely studied, however, the maneuvers of using o‐alkenyl phenols as starting materials are less explored. Herein, we report a general and efficient strategy via HNTf2/TMSOTf catalyzed cascade reaction with readily available o‐alkenyl phenols and aldehydes as starting materials, which provides 2,3‐disubstituted benzofuran derivatives in moderate to good yields. This method features metal‐free circumstances, broad substrate scope, mild reaction conditions, and easy scale preparation. [ABSTRACT FROM AUTHOR]

Dibenzofurans featuring a 2,2′-biazulene framework were prepared in good yields by Brønsted acid-promoted annulation of 2,3-di(1-azulenyl)benzofurans in 100% H3PO4. NMR, UV-Vis, and fluorescence spectroscopies were used to investigate the structural and optical properties of the products prepared. Remarkably, the annulated products exhibited fluorescence, with the longest wavelength of azulene derivatives reported to date, which extended into the near-infrared region under acidic conditions. [ABSTRACT FROM AUTHOR]

The selective hydrogenation of benzofurans in the presence of a heterogeneous non‐noble metal catalyst is reported. The developed optimal catalytic material consists of cobalt‐cobalt oxide core–shell nanoparticles supported on silica, which has been prepared by the immobilization and pyrolysis of cobalt‐DABCO‐citric acid complex on silica under argon at 800 °C. This novel catalyst allows for the selective hydrogenation of simple and functionalized benzofurans to 2,3‐dihydrobenzofurans as well as related heterocycles. The versatility of the reported protocol is showcased by the reduction of selected drugs and deuteration of heterocycles. Further, the stability, recycling, and reusability of the Co‐nanocatalyst are demonstrated. [ABSTRACT FROM AUTHOR]

A set of nine derivatives, including five brominated compounds, was synthesized and the structures of these novel compounds were confirmed using 1H and 13C NMR as well as ESI MS spectra. These compounds were tested on four different cancer cell lines, chronic myelogenous leukemia (K562), prostate cancer (PC3), colon cancer (SW620), human kidney cancer (Caki 1), and on healthy human keratocytes (HaCaT). MTT results reveal that two newly developed derivatives (6 and 8) exhibit selective action towards K562 cells and no toxic effect in HaCat cells. The biological activity of these two most promising compounds was evaluated by trypan blue assay, reactive oxygen species generation, and IL-6 secretion. To investigate the proapoptotic activity of selected compounds, the two following types of tests were performed: Annexin V Apoptosis Detection Kit I and Caspase-Glo 3/7 assay. The studies of the mechanism showed that both compounds have pro-oxidative effects and increase reactive oxygen species in cancer cells, especially at 12 h incubation. Through the Caspase-Glo 3/7 assay, the proapoptotic properties of both compounds were confirmed. The Annexin V-FITC test revealed that compounds 6 and 8 induce apoptosis in K562 cells. Both compounds inhibit the release of proinflammatory interleukin 6 (IL-6) in K562 cells. Additionally, all compounds were screened for their antibacterial activities using standard and clinical strains. Within the studied group, compound 7 showed moderate activity towards Gram-positive strains in antimicrobial studies, with MIC values ranging from 16 to 64 µg/mL.

Background & aimsA comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs.MethodsPROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment.ResultsOf 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21-53% of patients experienced >5% improved PROs while 23-36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35-55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements.ConclusionsIn real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities.Lay summaryPatients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.

Ion exchange, as a postsynthetic transformation strategy, offers more flexibilities in controlling material compositions and structures beyond direct synthetic methodology. Observation of such transformation kinetics on the single-particle level with rich spatial and spectroscopic information has never been achieved. We report the quantitative imaging of anion exchange kinetics in individual single-crystalline halide perovskite nanoplates using confocal photoluminescence microscopy. We have systematically observed a symmetrical anion exchange pathway on the nanoplates with dependence on reaction time and plate thickness, which is governed by the crystal structure and the diffusion-limited transformation mechanism. Based on a reaction-diffusion model, the halide diffusion coefficient was estimated to be on the order of [Formula: see text] This diffusion-controlled mechanism leads to the formation of 2D perovskite heterostructures with spatially resolved coherent interface through the precisely controlled anion exchange reaction, offering a design protocol for tailoring functionalities of semiconductors at the nano-/microscale.

Poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors are a class of anticancer drugs that block the catalytic activity of PARP proteins. Optimization of our lead compound 1 (( Z)-2-benzylidene-3-oxo-2,3-dihydrobenzofuran-7-carboxamide; PARP-1 IC50 = 434 nM) led to a tetrazolyl analogue (51, IC50 = 35 nM) with improved inhibition. Isosteric replacement of the tetrazole ring with a carboxyl group (60, IC50 = 68 nM) gave a promising new lead, which was subsequently optimized to obtain analogues with potent PARP-1 IC50 values (4-197 nM). PARP enzyme profiling revealed that the majority of compounds are selective toward PARP-2 with IC50 values comparable to clinical inhibitors. X-ray crystal structures of the key inhibitors bound to PARP-1 illustrated the mode of interaction with analogue appendages extending toward the PARP-1 adenosine-binding pocket. Compound 81, an isoform-selective PARP-1/-2 (IC50 = 30 nM/2 nM) inhibitor, demonstrated selective cytotoxic effect toward breast cancer gene 1 ( BRCA1)-deficient cells compared to isogenic BRCA1-proficient cells.

A class of translation inhibitors, exemplified by the natural product rocaglamide A (RocA), isolated from Aglaia genus plants, exhibits antitumor activity by clamping eukaryotic translation initiation factor 4A (eIF4A) onto polypurine sequences in mRNAs. This unusual inhibitory mechanism raises the question of how the drug imposes sequence selectivity onto a general translation factor. Here, we determined the crystal structure of the human eIF4A1⋅ATP analog⋅RocA⋅polypurine RNA complex. RocA targets the "bi-molecular cavity" formed characteristically by eIF4A1 and a sharply bent pair of consecutive purines in the RNA. Natural amino acid substitutions found in Aglaia eIF4As changed the cavity shape, leading to RocA resistance. This study provides an example of an RNA-sequence-selective interfacial inhibitor fitting into the space shaped cooperatively by protein and RNA with specific sequences.

Essential oils are known to possess many biological properties such as antimicrobial and antioxidant activities. Plumeria alba flowers are used in traditional remedies for diarrhea, cough, fever, and asthma treatment. This work evaluated the chemical composition and the biological activities of essential oils obtained from the flowers and leaves of Plumeria alba. The essential oils were extracted using the Clevenger-type apparatus and characterized using GC-MS. In the flower essential oil, a total of 17 compounds were identified, with linalool (23.91%), α-terpineol (10.97%), geraniol (10.47%), and phenyl ethyl alcohol (8.65%) being abundant. In the leaf essential oil, a total of 24 compounds were identified, with benzofuran, 2,3-di, hydro-(3.24%), and muurolol (1.40%) being present. Antioxidant activities were assessed using hydrogen peroxide scavenging, phosphomolybdenum, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assays. Antimicrobial activities were assessed through a microdilution assay. The essential oil showed antimicrobial activity against test microorganisms with minimum inhibitory concentrations ranging from 25.0 to 50.0 mg/mL. Biofilm inhibition ranged from 27.14 ± 1.0 to 58.99 ± 0.6 mg/mL. The essential oil exhibited total antioxidant capacities which ranged from 17.5 μg/g AAE to 83 μg/g AAE in the phosphomolybdenum assay. The IC50 values in the DPPH and hydrogen peroxide radical scavenging assays for both flowers and leaves ranged from 18.66 μg/mL to 38.28 μg/mL. Both essential oils also displayed good antibiofilm activities, with the concentration required for half-maximal inhibition of biofilm formation being ∼60 mg/mL for both oils. This study shows that essential oils of Plumeria alba possess good antioxidant and antimicrobial activities and could be used as a source of natural antioxidants and antimicrobial agents. [ABSTRACT FROM AUTHOR]