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A new series of N -phenyl-carbazole (N-phCbz) appended pyranones were designed and synthesized using α-oxo-ketene- S , S -acetal under mild reaction conditions in good yields. The reactivity of donor-acceptor (D-A)-based 2 H -pyranones was utilized to develop their ring-transformed benzene-cored N -phenyl-carbazole derivatives. All the synthesized carbazole-based pyranones showed aggregation-induced emission (AIE) characteristics in 80–99% water fraction (fw) in DMSO. Among all the synthesized compounds, 6-(4-(9 H -carbazol-9-yl)phenyl)-4-(methylthio)-2-oxo-2 H -pyran-3-carbonitrile exhibited excellent AIE behavior with ca. 70-fold increase in fluorescence in 80% fw at 550nm. Furthermore, this compound showed exceptionally high fluorescence in nonpolar solvent (THF) as compared to polar solvents such as DMSO (ca. 200-fold increase in fluorescence). The DFT, DSC, and TGA analyses of the synthesized D-π-A compounds suggested the strong electron-donor ability of N-phCbz, with good thermal stability in the range of 231–393 °C. These N -phenyl-carbazole-appended pyranones with interesting AIE properties have great potential as probes for bioimaging applications as well as for optoelectronic materials. [ABSTRACT FROM AUTHOR]

This investigation presents a novel, cost-effective approach for creating a 2-pyridone core substituted with an ester group through intramolecular rearrangement. This one-step transformation involves an amide-mediated intramolecular transformation of a pyranone to pyridone scaffold, followed by alcoholic-mediated ester formation, in 75–85% yield. Deuterated alcohol was used to confirm the esterification under alcoholic conditions. The reaction requires a nucleophile source from the solvent, which was observed by performing the reaction of three derivatives in CD3 OD to obtain the desired carboxylate compounds, replacing -OR with -OCD3. All synthesized compounds were characterized by spectroscopic analysis, and six selected compounds were further confirmed by single-crystal X-ray diffraction studies. [ABSTRACT FROM AUTHOR]

A sustainable methodology for the synthesis of pyrano [2,3-d] pyrimidine scaffolds have been developed, employing the Knoevenagel-Michael tandem cyclocondensation reaction of barbituric acid/1,3-dimethylbarbituric acid, malononitrile, and aryl aldehydes. This study elucidates the advancement of a sustainable and environmentally conscious approach to synthesizing this category of chemical compounds. In the present investigation, a novel photosensitizer comprising proflavine (PFH+) bio-photocatalyst was employed in an aqueous medium, subjected to air atmosphere at room temperature, and stimulated by a blue-light-emitting diode (LED) to harness renewable energy. The fundamental objective of this initiative is to utilize a photosensitizer (PS) biocatalyst that has been recently developed, can be conveniently acquired, and is priced affordably. The proflavine (PFH+) photocatalyst, demonstrates the ability to initiate photoinduced-electron transfer (PET) through exposure to visible light. This property endows the photocatalyst with a practical and efficient method of achieving high effectiveness, energy efficiency, and environmentally friendly outcomes. The current research endeavor has the objective of examining the turnover number (TON) and turnover frequency (TOF) pertaining to pyrano [2,3-d] pyrimidine scaffolds. Moreover, it has been validated that cyclization at the gram-scale is a feasible approach that can be employed in various industrial settings. [ABSTRACT FROM AUTHOR]

Rice blast disease, caused by Magnaporthe oryzae, is the most devastating cereal killer worldwide. Note that melanin pigment is an essential factor of M. oryzae virulence, thus fungicides interfering with melanin biosynthesizing enzymes would reduce the pathogenicity. Scytalone dehydratase (SDH) is the key target for commercial fungicides, like carpropamid, due to its role in the dehydration reaction of the fungal melanin pathway. However, a single-point mutation (V75M) in SDH elicits resistance to carpropamid. A lack of effective fungicides against this resistant strain expedited the quest for novel bioactive inhibitors. Currently, bacterial endophytes like Streptomyces have been heralded for synthesizing bioactive metabolites to protect plants from phytopathogens. The literature search led to the identification of 21 Streptomyces spp. symbionts of paddy that can suppress M. oryzae growth. An antiSMASH server was used to explore Streptomyces spp. gene clusters and found 4463 putative metabolites. Besides, 745 unique metabolites were subjected to a series of virtual screening techniques. Ideally, this process identified five potential SDH inhibitors. The docking result highlights that the metabolite pseudopyronine A interacted hydrophobically with both Val75 of SDHWT and Met75 of SDHV75M targets. Moreover, pseudopyronine A has a higher binding free energy with SDHWT (− 89.94 kcal/mol) and SDHV75M (− 71.95 kcal/mol). Interestingly, the pyranones scaffold of pseudopyronine A was reported for antifungal activity against phytopathogens. Dynamic behavior confirms that pseudopyronine A has excellent conformational states with both SDHWT and SDHV75M. Altogether, we hope that this study creates a new avenue for the discovery of novel phytopathogen inhibitors from endophytes. [ABSTRACT FROM AUTHOR]

Exclusive formation of 5‐aryl‐2‐trimethylsilyl‐4H‐pyran‐4‐ones is accomplished by a regioselective cyclization of 2‐aryl‐1‐ethoxy(hydroxy)‐5‐(trimethylsilyl)pent‐1‐en‐4‐yn‐3‐ones. This cyclization occurs in a 6‐endo‐dig mode through addition to the β‐atom of the TMS substituted triple bond. The reaction was found to be general for a range of ethoxyenynones upon heating in glacial acetic acid and for analogous hydroxyenynones in diphenyl ether. Plausible mechanistic explanation and possible post‐modifications of resulting pyranones are offered. [ABSTRACT FROM AUTHOR]

An efficient synthesis of (13α)-estrone derivatives containing pyran, isoxazole, or pyrazole moieties on the A-ring was performed based on difluoroborate complexes using the chelate methodology. Difluoroborate complexes were synthesized from (13α)-2-acetyl-3-hydroxyestra-1(10),2,4-trien-17-one. [ABSTRACT FROM AUTHOR]

Four undescribed pyranone derivatives, named ascomycopyrones A–D (1–4), as well as one known analogue simplicilopyrone (5) (this is the first study to report the absolute configuration), were isolated from the endophytic fungus Ascomycota sp. FAE17 derived from the flowers of Scutellaria formosa. The structures of these pyranones were identified by comprehensive spectroscopic and MS analyses, and the absolute configurations were determined by their experimental and quantum chemical electronic circular dichroism (ECD) calculations. All isolated compounds were tested for various bioactivities, including antibacterial, cytotoxic activity, and NO inhibitory activity. Unfortunately, none of the compounds showed significant bioactivities. [ABSTRACT FROM AUTHOR]

Two novel tandem sequences for stereoselective synthesis of elaborate hydropyranones are reported. The first one relies on an aldol‐lactonization procedure of a chiral enolate with an unprotected aldehyde, while the second one is based on a challenging dienolate ketone addition with concomitant cyclization and substrate controlled reduction. Both approaches proceed with high efficiency and stereoselectivity and enable very short accesses to the authentic pyranone subunit of the complex polyketide tuscolid and will be important to develop a first total synthesis of this structurally unique macrolide and to evaluate the tuscolid‐tuscoron rearrangement. [ABSTRACT FROM AUTHOR]

The monofluoroalkenes are found widespread applications in areas such as bioactive molecules, materials science and synthetic organic chemistry, therefore, investigating efficient methodologies to construct monofluoroalkenes is still in demand. In this paper, we reported an efficient synthesis of monofluoroalkenyl substituted pyranones/pyridones by using the gem -difluorocyclopropanes (gem -DFCPs) as monofluoroalkenyl precursors. In the presence of Palladium catalyst, the monofluoroalkenyl group was introduced into the C3 positions of pyranones/pyridones successfully. The reaction was featured with high regioselectivity, mild conditions, broad substrate scope, easy to scale up synthesis, which provided a novel avenue for the late-stagy modification of pyranones/pyridones. To create your abstract, type over the instructions in the template box below.Fonts or abstract dimensions should not be changed or altered. [Display omitted] • Ring-opening defluorinative coupling reaction of gem -DFCPs. • First introduce the monofluoroalkenyl groups at the C-3 position of pyranones/pyridones. • Wide substrate scope with high regioselectivity. • Novel scaffolds for drug discovery. [ABSTRACT FROM AUTHOR]

This study developed a novel photocatalytic method to synthesize pyranones from furfural alcohols. By using 0.2 mol% equivalent of tris-Ir(ppy)3 as a photocatalyst under visible light and O2 as the reaction atmosphere, furfural alcohols were rapidly oxidized and hydrolyzed in the aqueous reaction solution to produce diol intermediates, which further underwent hydrolysis, furan ring-opening and rearrangement to form the final product pyranones. The entire reaction was carried out at room temperature with a yield as high as 86% and a conversion efficiency of 90%. This method is general and suitable for furfural alcohols with different substituted groups on the 5- and α-OH sites. We used in situ IR and real-time NMR to examine the reaction kinetics, GC-MS and isotope-labeling experiments to track the source of atom transfer in the reaction, and EPR to identify the singlet oxygen. The results showed that the reaction followed a first-order rate equation, and O2 oxidation was the rate-determining step. The transferred H atom came from the H2O solvent, the O atom from the O2 atmosphere, and the singlet oxygen from the O2 photocatalysis. The UV-vis and cyclic voltammetry results indicated that this photocatalysis reaction involved a single electron transformation process. We also used DFT calculation to simulate the reaction routes and showed that the tris-Ir(ppy)3 photocatalysis O2 oxidation in the aqueous phase was the critical step of endoperoxide oxidation, which differs from oxygen onium ion oxidation in the classic Achmatowicz rearrangement reaction. Our method can carry out a 10.0 gram-scale reaction with a 78% yield. It avoids stoichiometric consumption of toxic or corrosive oxidative reagents in the Achmatowicz rearrangement reaction. It may provide a novel, efficient, and "green" alternative to the Achmatowicz rearrangement reaction. [ABSTRACT FROM AUTHOR]

[Display omitted] Spirocyclization of morpholinium 3-[(aryl)(1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)methyl]-6-methyl-2-oxo-2 H -pyran-4-olate by the action of sodium acetate- N -bromosuccinimide system in ethanol at room temperature results in spiro[furo[3,2- c ]pyran-2,5'-pyrimidine] derivatives in 92–98% yields, the protocol allowing to avoid column chromatography purification. This new highly efficient and facile procedure is a convenient way to substituted unsymmetrical spiro scaffold containing pyrimidine-2,4,6-trione and 2,3-dihydro-4 H -furo[3,2- c ]pyran-4-one fragments promising for biomedical applications. [ABSTRACT FROM AUTHOR]

A divergent copper-mediated cyclization between oxime acetates and distinct 1,3-cyclic dicarbonyl compounds such as 4-hydroxyquinolinones/pyranones/coumarins was developed. Using the same reaction conditions, an array of furan-fused heterocycles such as furoquinolinones/pyranones/coumarins were prepared in good to high yields. The products possess a less common substitution pattern than those in previous syntheses. The mildness of the protocol enables a broad scope without affecting sensitive functionalities such as azido, alcohol, terminal alkyne, alkyl ester, and alkyl halide groups. Mechanistic investigations infer a purely organometallic pathway, excluding the participation of radical intermediates. Ultimately, the heteroannulation was exploited as the key step in a short and high-yielding synthesis of the phytoestrogen coumestrol. [Display omitted] • The reaction allows the synthesis of a wide array of furan-fused quinolinones, pyranones, and coumarins. • The reaction conditions tolerate sensitive functionalities. • The operative mechanistic pathway is distinct from previous similar reactions. • Natural product coumestrol was effectively assembled using this method as a key step. [ABSTRACT FROM AUTHOR]

Background: Chiral furfuryl alcohols are important precursors for the synthesis of valuable functionalized pyranones such as the rare sugar L-rednose. However, the synthesis of enantiopure chiral biobased furfuryl alcohols remains scarce. In this work, we present a chemoenzymatic route toward enantiopure nitrogen-containing (R)- and (S)-3-acetamido-5-(1-hydroxylethyl)furan (3A5HEF) from chitin-derived N-acetyl-D-glucosamine (NAG). Findings: 3-Acetamido-5-acetylfuran (3A5AF) was obtained from NAG via ionic liquid/boric acid-catalyzed dehydration, in an isolated yield of approximately 31%. Carbonyl reductases from Streptomyces coelicolor (ScCR) and Bacillus sp. ECU0013 (YueD) were found to be good catalysts for asymmetric reduction of 3A5AF. Enantiocomplementary synthesis of (R)- and (S)-3A5HEF was implemented with the yields of up to > 99% and the enantiomeric excess (ee) values of > 99%. Besides, biocatalytic synthesis of (R)-3A5HEF was demonstrated on a preparative scale, with an isolated yield of 65%. Conclusions: A two-step process toward the chiral furfuryl alcohol was successfully developed by integrating chemical catalysis with enzyme catalysis, with excellent enantioselectivities. This work demonstrates the power of the combination of chemo- and biocatalysis for selective valorization of biobased furans. [ABSTRACT FROM AUTHOR]

A general [5+1] annulation reaction, which utilized 4-bromo- or 4-mesyloxy-but-2-enyl peroxides as unique five-atom bielectrophilic synthons to participate in the C–C and the subsequent umpolung C–O bond-forming reactions with C1 nucleophiles, has been developed for the facile synthesis of 2,2-disubstituted dihydropyrans in high yields under mild basic conditions. The dihydropyrans, which are readily prepared on a gram scale by this new method, can be flexibly transformed into the biologically important tetrahydropyrans and pyranones in 1–2 steps. [ABSTRACT FROM AUTHOR]

Topomer CoMFA was used to build a three-dimensional quantitative structure-activity relationship (3D-QSAR) model for 18 pyranones in this paper,with key parameters as follows:N= 3, F= 23. 879,r² = 0. 888,q² = 0. 554,r2derr = O. 20,q2derr = 0. 40, SEE= 0. 199,respectively. The results show that this model had a good predictive ability. Topomer search was employed to select in ZINC molecular database,as a results total of 7 new compounds with better activity than template molecules were designed. The interaction mode between the new compounds and the macromolecular protein lEEO was explored by Surflex-dock, the results showed that the ligand molecules acted obviously with B/ ARG274,B/ ARG312,B/ LYS67 and other sites of lEEO. [ABSTRACT FROM AUTHOR]

A highly enantioselective intramolecular NHC‐catalyzed approach for the synthesis of benzo‐fused pyranones bearing quaternary stereocenter is described. The developed methodology is based on annulation reaction between acyl anion intermediates and β,β‐disubstituted Michael acceptors. The reaction offers streamlined and effective access to target products in a highly stereoselective manner. [ABSTRACT FROM AUTHOR]

The first‐time reported nitrogen source‐based chemoselectivity of dehydroacetic acid (DHA)‐derived enones has been tuned by isoniazid (INH), and phenylhydrazines respectively. When INH a first‐line antitubercular drug, was employed as a new surrogate for nitrogen source, preferentially unconventional 1,3‐dicarbonyl addition occurred, providing a series of fused 3‐styryl pyrano[2,3‐c]pyrazolones in good yields. While in the presence of phenylhydrazines and molecular iodine, the reaction was proceeded via oxidative annulation across enone framework, resulting in the efficient and straightforward access to 3‐pyrazolyl pyranones. [ABSTRACT FROM AUTHOR]

Development of small molecule compounds that target several cancer drivers has shown great therapeutic potential. Here, we developed a new generation of highly potent thienopyranone (TP)-based inhibitors for the BET bromodomains (BDs) of the transcriptional regulator BRD4 that have the ability to simultaneously bind to phosphatidylinositol-3 kinase (PI3K) and/or cyclin-dependent kinases 4/6 (CDK4/6). Analysis of the crystal structures of the complexes, NMR titration experiments and IC50 measurements reveal the molecular basis underlying the inhibitory effects and selectivity of these compounds toward BDs of BRD4. The inhibitors show robust cytotoxic effects in multiple cancer cell lines and induce cell-cycle arrest and apoptosis. We further demonstrate that concurrent disruption of the acetyllysine binding function of BRD4 and the kinase activities of PI3K and CDK4/6 by the TP inhibitor improves efficacy in several cancer models. Together, these findings provide further compelling evidence that these multi-action inhibitors are efficacious and more potent than single inhibitory chemotypes. [ABSTRACT FROM AUTHOR]

In this work, new furopyranone‐ and furocoumarin‐chromone conjugates were successfully synthesized via the one‐pot three‐component condensation reactions of 3‐formylchromone derivatives, 4‐hydroxy‐6‐methylpyrone or 4‐hydroxycoumarin and alkyl or aryl isocyanides in refluxing toluene within 2 h. Molecular docking studies on cyclooxygenase enzymes (COX‐1, COX‐2) indicated that most derivatives have greater or moderate binding affinities than 3‐formylchromone which was used as a reference compound. Even some of the new products showed comparable binding energy towards the relative co‐crystalized ligand into COX‐1 and COX‐2. In general, all of the new products formed one to three hydrogen bonds with amino acid residues in the active site of both enzymes. Furthermore, the cytotoxicity activity of some selected compounds was investigated against human foreskin fibroblast cells (BJ) and human breast cancer cells (MDA‐MB‐231) using the MTT assay. All selected compounds exhibited significant cell growth inhibitory against cancerous cells with varied potencies when compared to 3‐formylchromone. However, they were much less toxic against normal cells. A one‐pot synthesis of new chromone‐based furopyranone and furocoumarin compounds has been developed. Some of the synthesized furopyranone‐ and furocoumarin‐chromone conjugates have been found to show good potent anticancer activities against two different cancer cell lines. Molecular docking studies were performed on cyclooxygenase enzymes (COX‐1, COX‐2). [ABSTRACT FROM AUTHOR]

In this paper, we describe the use of p‐TSA based Deep Eutectic Solvents (DESs) as alternative environmental‐friendly "active" solvents for the microwave‐mediated synthesis of 6‐substituted 3,4‐fused 2‐pyranones, and in particular isocoumarins, starting from 2‐alkynyl‐(hetero)arylcarboxylates. When the alkyne terminus bears a neutral or an electron‐donating group (EDG), the reactions are fast, clean and highly regioselective, to give the 6‐endo‐dig cyclization products in good to excellent yields. For substrates bearing an electron‐withdrawing group (EWG) on the alkyne end, the regioselectivity can be tuned by adding a small amount of silver(I) triflate as co‐catalyst. DES was demonstrated to be reusable without loss of efficiency in terms of reaction yields. Based on experimental evidence and previous findings, two competitive mechanisms working simultaneously are proposed to explain the outcomes and the regioselectivity issues. An acidic Deep Eutectic Solvent is an alternative environmental‐friendly "active" media for the microwave‐mediated synthesis of 6‐substituted 3,4‐fused 2‐pyranones. [ABSTRACT FROM AUTHOR]

Four novel fluorescent cores bearing a transformable functional group based on a π-expanded naphthalimide including a fused pyranone or furan ring have been prepared. Fluorescent probes LysoSers 13–16 for lysosomal targeting have been tested. Co-localization with a commercial lysosome specific marker confirmed that the LysoSers labeled the lysosomal compartment with high selectivity. The LysoSers show excellent brightness and low toxicity. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new 8,8ˈ-binaphthopyranone (mycopyranone, 1) was discovered and elucidated. • Absolute configuration was elucidated via NOESY, Mosher's esters, and ECD data. • Active in vitro vs a clinically-relevant methicillin-resistant S. aureus strain. • Molecular docking studies suggests binding to the FtsZ (tubulin-like) protein. Abstract A new 8,8ˈ-binaphthopyranone (mycopyranone, 1) was isolated from a solid fermentation of Phialemoniopsis sp. (fungal strain MSX61662), and the structure was elucidated via analysis of the NMR and HRESIMS data. The axial chirality of 1 was determined to be M by ECD. The central chirality at C-4/C-4ˈ was assigned through a modified Mosher's method, while the absolute configuration at C-3/C-3ˈ was deduced based on analysis of the 3 J H-3-H-4 values and NOESY correlations. Compound 1 was evaluated for its antimicrobial properties against Staphylococcus aureus SA1199 and a clinically relevant methicillin-resistant S. aureus strain (MRSA USA300 LAC strain AH1263). Compound 1 inhibited the growth of both strains in a concentration dependent manner with IC 50 values in the low μM range. Molecular docking indicated that compound 1 binds to the FtsZ (tubulin-like) protein in the same pocket as viriditoxin (2), suggesting that 1 targets bacterial cell division. [ABSTRACT FROM AUTHOR]

The design and synthesis of organic molecules having aggregation induced emission (AIE) property has been a prime area of research in recent years. In this regard, we have synthesized new pyranone based AIEgens with interesting photophysical properties. The synthesized donor-acceptor based pyranones 3 and 4a-d show multicolour emission in the range of 476-585 nm in solid state. The compound 3 also showed blue emission (485 nm) in DMSO solution and surprisingly exhibits orange emission (572 nm) with remarkable bathochromic shift in 99% water in DMSO due to AIE characteristics. The detailed study of AIE behaviour of 3 was carried out in increasing fraction of water (0-99%) in THF, the intensity of emission at 485 nm gradually increased upto 80% of water and then decreased at 90% water. Interestingly, the THF solution of 3 in 99% water showed remarkable bathochromic shift (~100 nm) of emission maximum from blue (λmax 485 nm) to orange region (λmax 585 nm) due to formation of nano-aggregates leading to restriction in intramolecular rotation (RIR). The time-correlated single photon counting (TCSPC) analysis of 3 in the water−THF (99:1) mixture showed an average lifetime of 4.8 ns for these nano-aggregates. The pyrrolyl-pyranone 3 having Solution-Solid Dual Emissive (SSDE) characteristics may be utilized in exploring its application in both biomedical and material research fields. [ABSTRACT FROM AUTHOR]

The novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde (2) was efficiently synthesized from Vilsmeier–Haack formylation of 3‐(1‐ethy1‐4‐hydroxy‐2‐oxo‐(1H)‐quinolin‐3‐yl)‐3‐oxopropanoic acid (1). The aldehyde 2 was allowed to react with some nitrogen nucleophiles producing a variety of hydrazones 3–7. Reaction of aldehyde 2 with hydrazine hydrate and hydroxylamine hydrochloride afforded pyrazole and isoxazole annulated pyrano[3,2‐c]quinoline‐2,5(6H)‐dione, respectively. The reactivity of aldehyde 2 was examined toward some active methylene nitrile, namely, malononitrile, ethyl cyanoacetate, and cyanoacetamide leading to 2‐iminopyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines 10–12, respectively. Also, some novel pyrazolo[4″,3″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines (13, 14) and thiazolo[5″,4″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines (15, 16) were synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data. [ABSTRACT FROM AUTHOR]

The first stereoselective total synthesis of cytotoxic diacetylene pyranone B is described. The key steps involved in the synthesis are base-induced elimination protocol to generate the chiral acetylenic alcohol and selective cross-coupling of unsymmetrical terminal acetylenes. [ABSTRACT FROM AUTHOR]

Abstract In this study, three novel series of benzoxazinone, benzothiopyranone and benzopyranone derivatives were designed through scaffold morphing from benzothiazinones to target DprE1. All compounds were evaluated for their in vitro activities against Mycobacterium tuberculosis and cytotoxicity against Vero cell line. Among these three series, the benzothiopyranone series displayed excellent antimycobacterial activity and low cytotoxicity. In particular, compound 6b exhibited potent in vitro activity against both drug-susceptible and drug-resistant tuberculosis clinical strains with MICs <0.016 μg/mL. In addition, compound 6b demonstrated excellent ADME/T and PK properties and potent in vivo efficacy with bactericidal activity in an acute mouse model of tuberculosis. The antituberculosis effect of compound 6b is most likely attributed to its excellent anti-DprE1 activity. As such, compound 6b is under evaluation as a potential clinical candidate for treatment of tuberculosis. The current study provided new insight into the structural and pharmacological requirements for DprE1 inhibitors as potent antitubercular agents. Graphical abstract Image 1 Highlights • The benzothiopyranones displayed excellent anti-TB activity and low cytotoxicity. • Compound 6b exhibited good inhibitory activity against DprE1. • Compound 6b exhibited potent in vitro activity against both DS-TB and DR-TB. • Compound 6b displayed superior ADME/T and PK properties. • Compound 6b demonstrated potent in vivo efficacy in an acute mouse model of TB. [ABSTRACT FROM AUTHOR]

Pyranopyridine derivatives are an important class of heterocyclic compounds due to their biological activities such as antitumor and antibacterial. However, conventional procedures for their synthesis produce large amounts of toxic by-products. Therefore, there is a need to develop simple, efficient and environmentally benign procedures. Here, a one-pot multicomponent protocol is designed for the synthesis of pyrano[2,3-b]pyridone derivatives by reaction of equimolar amounts of 6-hydroxy-1,4-dimethyl-1,2-dihydropyridines, aryl aldehydes and malononitrile, using both microwave heating and solar thermal energy in aqueous EtOH (50%) in the presence of a catalytic amount of K2CO3. The products were obtained in 84-90% yields in 10-20 min by microwave heating, and in 90-96% yields in 2-3 h using solar energy. [ABSTRACT FROM AUTHOR]

A regioselective magnesiation of the 2-pyrone scaffold was developed. Magnesiation of this heterocycle by using TMPMgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by trapping reactions with electrophiles such as aldehydes, allylic bromides, acid chlorides, and aryl iodides provided functionalized 2-pyrones. Furthermore, methyl coumalate and 3,5-dibromo-2H-pyran-2-one were zincated by using TMPZnCl·LiCl to afford zincated heterocycles, which reacted with typical electrophiles. A second magnesiation at position C3 of the 2-pyrone scaffold was achieved by using TMPMgCl·LiCl. Also, the zincation of the 4-pyrone scaffold at position C2 is reported, leading to functionalized 4- pyrones. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The naphthopyranones showed immunomodulatory potential. • Immunomodulation was reported by TNF-a, IL-6 and NO inhibition. • Synergism was evidenced through iNOS inhibition and NO scavenging. • Cytotoxic activity in AGS cell line was reported. Abstract The naphthopyranones paepalantine and 5-methoxy-3,4-dehydroxanthomegnin isolated from Paepalanthus sp, showed in previous studies antioxidant, anti-inflammatory, antitumour and antimicrobial potential, such as anti- Helicobacter pylori activity. H. pylori infection is one of the main causes of gastric cancer, causing an excessive inflammatory response through the neutrophils and macrophages infiltration, increasing the release of reactive species and thus inducing the production of pro-inflammatory mediators. In the present study, immunomodulatory activity of naphthopyranones in LPS-stimulated macrophages and cytotoxic action in gastric adenocarcinoma cell lines was evaluated. The potential of interaction of these substances in the iNOS binding site was investigated by molecular docking. Cytotoxic activity in gastric adenocarcinoma cells (AGS) was evaluated by the MTT assay. The results evidenced immunomodulatory potential by inhibiting the pro-inflammatory cytokines and nitric oxide produced by LPS-stimulated macrophages. Cytotoxic activity in AGS cell line was also reported. The results indicated that the studied naphthopyranones are viable alternatives in the treatment and prevention of H. pylori infection as well as the diseases related to this infection, especially gastric cancer. [ABSTRACT FROM AUTHOR]

A method of synthesis is proposed and alternative mechanisms of formation of 1,3,6-trimethyl-6Hpyrano[ 4,3-b]carbazole-2-pyrylium perchlorate and its recyclization to 1,3,6-trimethyl-6H-pyrido[4,3-b]- carbazole, a close analog of the natural alkaloid ellipticine, are discussed. [ABSTRACT FROM AUTHOR]

Abstract Drug-resistant bacteria associated with biofilm formation are rapidly on the rise, requiring novel therapeutic options to combat biofilm induced drug-resistance. In this study, a class of 3-hydroxy-2-(phenylhydroxy-methyl)-6-methyl-4 H -pyran-4-one derivatives (1a - 1e) were found by screening of an in-house compound library to be potential Pseudomonas aeruginosa biofilm inhibitors. Thirty one novel 2-substituted 3-hydroxy-6-methyl-4 H -pyran-4-one derivatives were synthesized and assayed for their biofilm inhibitory activity. A promising biofilm inhibitor 6a was identified, and showed an obvious biofilm inhibitory effect even at a concentration of 2.5 μM. Further mechanism studies revealed that 6a only shows inhibitory effects on the expression of pqsA-gfp in a fluorescent reporter strain, and the production of a PQS- regulated virulence factor, pyocyanin. This indicates that this type of compound exercises its anti-biofilm activity specifically through the PQS pathway. Novel chemical biofilm inhibitors are described here and guard against biofilm formation associated with Pseudomonas aeruginosa infections. Graphical abstract Image 1 Highlights • Four series of 2-substituted 3-hydroxy-6-methyl-4 H -pyran-4-one derivatives were synthesized. • Potent biofilm inhibitor 6a exhibited excellent Pseudomonas aeruginosa biofilm inhibitory effect were identified. • The PQS pathway specific anti-biofilm mechanism of this type of compound was uncovered. [ABSTRACT FROM AUTHOR]

A simple green method has been developed for the synthesis of a series of new 3-phenyl-6-(substituted)-thiopyrano[2,3-d]thiazole-2,5,7(6H)-triones, 6-cyano-2-oxo-3-phenyl-thiopyrano[2,3-d]thiazoles, 3-phenyl-3,5,5a,11b-tetrahydro-2H,6H-chromeno-[4′,3′:4,5]thiopyrano[2,3-d]thiazole-2,6-dione and 5-amino-6-cyano-2-oxo-3-phenyl-3,7-dihydro-2H-thiopyrano[2,3-d]thiazoles via hetero-Diels-Alder reaction by conventional method and green method using lemon juice as natural acid. The structure of all the newly synthesized compounds was interpreted by elemental analyses and spectral data. The synthesized compounds were evaluated for their in vitro antibacterial activity against some pathogenic bacteria. This study is a platform for the future design of more potent antimicrobial agents. [ABSTRACT FROM AUTHOR]

Abstract: Intermolecular asymmetric gold catalysis involving alkyne activation presents a significant challenge due to its distinct mechanistic mode from other metals. Herein, we report a highly enantioselective synthesis of α,β‐unsaturated δ‐lactones from [4+2] annulation of propiolates and alkenes in upto 95 % ee. Notably, for the desired chiral recognition, the choice of 1,1,2,2‐tetrachloroethane as solvent was found to be crucial. Furthermore, an anionic surfactant (sodium dodecyl sulfate) improved the product selectivity in the divergence of the cyclopropyl gold carbene intermediate. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • One-pot synthesis of 6-oxo-7-aryl-6,7-dihydrochromenopyrano[2,3- b ]pyridines was described. • Guanidine hydrochloride as the organocatalyst was used. • Aromatic aldehydes containing various functional groups are well tolerated in the reaction. • Double heterocyclization was carried out in the reaction. Abstract A simple and efficient protocol has been developed for the construction of novel 6-oxo-7-aryl-6,7-dihydrochromenopyrano[2,3- b ]pyridine derivatives using one-pot, three-component cyclocondensation of 4-hydroxycoumarin, various aromatic aldehydes and 2-aminoprop-1-ene-1,1,3-tricarbonitrile using 10 mol % guanidine hydrochloride as the organocatalyst under solvent-free conditions at 90 °C for the first time. The significant features of this protocol are operational simplicity, provide good to high yields, avoidance of toxic solvents, straightforward work-up, no column chromatographic purification and atom-economy which is considered to be relatively environmentally benign. [ABSTRACT FROM AUTHOR]

Abstract: Alcohol dehydrogenases can act as powerful catalysts in the preparation of optically pure γ‐hydroxy‐δ‐lactones by means of an enantioconvergent dynamic redox isomerization of readily available Achmatowicz‐type pyranones. Imitating the traditionally metal‐mediated “borrowing hydrogen” approach to shuffle hydrides across molecular architectures and interconvert functional groups, this chemoinspired and purely biocatalytic interpretation effectively expands the enzymatic toolbox and provides new opportunities in the assembly of multienzyme cascades and tailor‐made cellular factories. [ABSTRACT FROM AUTHOR]

Abstract Phenylzinc bromide enables a pseudo three-component reaction of methyl glutaconate and aromatic aldehydes. Unsaturated trisubstituted δ-valerolactones (dihydropyranones) are obtained in fair to good yields by an aldol/aldol/elimination/lactonization domino process that allows the formation of four new bonds in a single step. A putative reaction mechanism is proposed. [ABSTRACT FROM AUTHOR]

Chemical investigation of the roots of Croton crassifolius led to the isolation of five pyran-2-one derivatives, including two brand new compounds ( 1 – 2 ), one new natural product ( 3 ) and two known compounds ( 4 – 5 ). Their structures and absolute configurations were established by spectroscopic analyses as well as comparison between the calculated optical rotation (OR) values with the experimental data. Interestingly, the new compound 1 showed an unusual negative chemical shift at H-11. It is well known that negative chemical shift values of 1 H NMR spectrum are extremely rare in natural products. Such a negative chemical shift of 1 H NMR spectrum was reproduced by density functional theory (DFT) calculations and explained by the shielding effect from the pyran-2-one ring over the hydrogen atom in the 3D conformations. Then, MTT assay was applied to evaluate the cytotoxicity of the isolated compounds ( 1 – 5 ) against two liver cancer cell lines (HepG2 and MHCC97H). The results suggested that compound 1 displayed the highest cytotoxicity with an IC 50 value of 9.8 μM against HepG2 cells. Moreover, there was no obvious cytotoxicity of compounds 1 – 5 on normal liver cell line LO2. Furthermore, the mechanism of apoptosis induction in compound 1 -treated HepG2 cells was investigated. The results showed that compound 1 could induce apoptosis via p53-mediated Ras/Raf/ERK suppression in HepG2 cells. [ABSTRACT FROM AUTHOR]

Pyrano[3,2-c]pyranone is an important structural motif present in many natural products exhibiting diverse biological activities. Two series of carbohydrate fused pyrano[3,2-c]pyranone derivatives (n = 20) were efficiently synthesized starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxycoumarins in a very short reaction time (10 min) under microwave assisted conditions. The anticancer activity of these synthesized pyrano[3,2-c]pyranones was determined in detail through cellular assays against MCF-7 (breast), MDA-MB-231 (breast) and HepG2 (liver) cancer cell lines. The newly synthesized pyrano[3,2-c]pyranones were screened for their cell-viability and anti-proliferative activity against MCF-7, MDA-MB-231 and HepG2 cell lines. Compounds 12, 13 and 14 exhibited high growth inhibitory potencies selectively against MCF-7 cells with half-maximal inhibitory concentration (IC50) values of 19.9, 14.5 and 10.9 μM respectively. Compounds 12, 13, 14, 15 and 19 inhibited the growth of MDA-MB-231 cells (breast) by 43, 44, 37, 31 and 45% respectively. However, no inhibitory effect was observed for these compounds in the human liver cancer cell line (HepG2) and normal cell lines (HEK293, human embryonic kidney cells). Mechanistic studies showed that these compounds alter the cell morphology and cause G2/M arrest in MCF-7. Further studies showed that compounds 12, 13 and 14 significantly inhibited cell migration which was accompanied by altered microtubule distribution. An enhanced accumulation of these compounds in cells was observed as compared to the 4-hydroxycoumarins precursor in the intracellular uptake assay. These findings confirm that carbohydrate fused pyrano[3,2-c]pyranones are better candidates for anticancer activity. [ABSTRACT FROM AUTHOR]

One-pot process was studied between a substituted 4-hydroxy-2Н-pyran-2-one and aromatic aldehydes and ammonium acetate in the conditions of modified Hantzsch reaction in acid environment under thermal and microwave activation. Arylmethylenebis-4-hydroxy-2Н-pyridin-2-ones, hydrochromenopyridinone, and their oxygen-containing heteroanalogs were isolated. A primary condensation was confirmed into bispyran-2-one adducts, and at the use of salicilaldehyde, into pyranochromene with subsequent recyclization of pyranone fragments in pyridinone ones. [ABSTRACT FROM AUTHOR]

A variety of novel heteroannulated pyrano[3,2- c ]quinolines 2 – 12 was efficiently synthesized via a domino ‘ Michael /retro- Michael /nitrile addition/heterocyclization’ reactions between 6-ethyl-5,6-dihydro-4,5-dioxo-4 H -pyrano[3,2- c ]quinoline-3-carbonitrile ( 1 ) and a diversity of carbon nucleophilic reagents. Pyrido[3′,2′:5,6]pyrano[3,2- c ]quinolines 2 – 6 were synthesized from ring opening ring closure reactions of carbonitrile 1 with some methylene active nitrile namely malononitrile, cyanoacetamide, N -phenylcyanoacetamide, (phenylthio)acetonitrile and ethyl cyanoacetate, respectively. Reactions of carbonitrile 1 with dimer malononitrile and cyanoacetohydrazide showed different behavior producing the novel heteroannulated pyranoquinoline derivatives 7 and 8 , respectively. Treatment of carbonitrile 1 with some methylene active ketones namely acetylacetone, acetoacetanilide, ethyl acetoacetate and ethyl benzoylacetate afforded pyrido[3′,2′:5,6]pyrano[3,2- c ]quinolines 9 – 12 , respectively. Structures of the synthesized products were deduced on the basis of their analytical and spectral data. [ABSTRACT FROM AUTHOR]

A novel library of pyrano[3,2- c ]chromene-3-carbonitrile and benzo[ g ]chromene-3-carbonitrile containing an aroyl or acetyl group moiety at 4-position has been extended by successive three-component reaction of 4-hydroxycoumarin or 2-hydroxy-1,4-naphthoquinone with phenylglyoxal monohydrate and a CH-acid like malononitrile/ethyl cyanoacetate/methyl cyanoacetate/cyanoacetamide under mild condition in ethanol. This approach for the preparation of novel polysubstituted pyrano[3,2- c ]chromene and benzo[ g ]chromene is distinguished with high atom-economy, good to high efficiencies, mild and metal-free conditions, simple workup and easy purification. [ABSTRACT FROM AUTHOR]

The new type of ‘on-solvent’ multicomponent reaction was found: transformation of benzaldehydes, malononitrile and 4-hydroxy-6-methylpyridin-2(1H)-one in the presence of sodium acetate as catalyst in a small amount of ethanol results in formation of substituted 2-amino-7-methyl-5-oxo-4-phenyl-5,6-dihydro-4H-pyrano[3,2-c]pyridine-3-carbonitriles in excellent 92-99% yields. This novel ‘one-pot’ process opens an efficient and convenient way to functionalize pyrano[3,2-c]pyridine systems, which are promising compounds for different biomedical applications. [ABSTRACT FROM AUTHOR]

Psychorubrin, a natural pyranonaphthoquinone found in different plants, has become an interesting compound in the search for new antimicrobial therapeutic agents. Here, we investigated the potential antagonistic activity of psychorubrin against planktonic and biofilm bacteria. First, psychorubrin was tested against several Gram-positive and Gram-negative bacteria strains by a broth microdilution susceptibility method. Second, bacterial killing assay, bacterial abundance, and membrane viability were evaluated. The nucleotide leakage assay was used to verify membrane destabilization while antibiofilm activities were analyzed by the effect on established biofilm, static biofilm formation, isolation of biofilm matrix assay and scanning electron microscopy. In parallel, the combinatorial effect of psychorubrin and chloramphenicol was evaluated by the checkerboard method. Psychorubrin was active against Gram-positive bacteria, showing rapid time-dependent kinetics of bacterial killing, amplified nucleotide leakage, and greater activity against the methicillin-resistant species (MRSA) Staphylococcus aureus 33591 and 33592 and Staphylococcus pyogenes 10096. Psychorubrin also interfered with the composition of the biofilm matrix by reducing the total content of carbohydrates and proteins. A synergic effect between psychorubrin and chloramphenicol was observed for S. aureus 33592 and S. pyogenes 10096 while an additive effect was detected for S. aureus 33591. Our findings demonstrate, for the first time, an antagonistic activity of psychorubrin against bacteria not only in their planktonic forms but also in biofilms, and identify bacterial membranes as primary targets for this compound. Based on these observations, psychorubrin has a good potential for the design of novel antimicrobial agents. [ABSTRACT FROM AUTHOR]

Taurine, a β -amino acid that is abundantly available in the tissues of human and animals, is efficiently used as a green bio-organic catalyst in the preparation of some of the biologically active barbituric and thiobarbituric acid derivatives. In the presence of taurine, 5-Arylidene (thio) barbituric acid derivatives were prepared via Knovenagel reaction between aldehydes and (thio)barbituric acid. Using this reagent also pyrano[2,3- d ]pyrimidinone(thione) derivatives were synthesized through a three-component reaction between aldehydes, (thio)barbituric and malononitrile. Both reactions are performed in water with good to excellent yields during acceptable reaction times. No organic solvent was used during reaction or separation steps and no extra-purification was exerted. Meanwhile, reusability of taurine was easy and noticeably high. [ABSTRACT FROM AUTHOR]

The stereo/regio/chemoselective syntheses of a library of novel spiro[acenaphthylene-1,3′-pyrrolizin]-2-one and spiro[acenaphthylene-1,5′-pyrrolo[1,2-c]thiazol]-2-one have been achieved through 1,3-dipolar cycloaddition. Intermediate azomethine ylides generated in situ from α-amino acids and acenaphthylene-1,2-dione react with α-aroylidine ketenedithioacetal (AKDTA) derivatives to give the target product in excellent yield under ultrasound irradiation. Further, spiro-S,S-acetals are converted to spiro-2H-pyranones by a one-pot cyclization strategy. [ABSTRACT FROM AUTHOR]

A bioinspired synthesis of chiral 3,4-dihydropyranones via S-to-O acyl-transfer reactions is described. Asymmetric Michael addition-lactonization reactions of β,γ-unsaturated α-keto esters with thioesters are catalyzed by proline-derived urea, providing 3,4-dihydropyranones and spiro-3,4-dihydrocoumarin-fused 3′,4′-dihydropyranones in high yield (up to 94%) with excellent stereoselectivities (up to >20:1 dr, 99% ee) under catalyst loadings as low as 1 mol %. [ABSTRACT FROM AUTHOR]

The pyranone functionalization of the upper rim of resorcinarene to provide the coumarin macrocycle called "coumarin[4]arene", possessing visible fluorescence and conformationally flexible behavior suitable for molecular recognition, has been successfully synthesized and characterized. [ABSTRACT FROM AUTHOR]

Four novel fluorescent whitening agents based on 4-methyl-2H,5H-pyrano derivatives of 2H-pyrido[1,2- a ]pyrimidine-2,4(3H)-dione were synthesized using a simple two step route. The structures were characterized by spectroscopy techniques such as, 1 H, 13 C NMR, and HRMS. Photophysical properties in various microenvironments were evaluated experimentally and correlated with optical absorption and fluorescence emission using global hybrid (B3LYP) and long range separated functional (CAM-B3LYP) with the Pople's 6–31G(d) basis set and in combination with polarizable continuum model. The experimental and theoretical photophysical properties were found in good agreement with each other. The excited state calculations revealed that the excitation values were in the range of 350–370 nm and emission values were in the range of 400–425 nm suggesting their potential application as fluorescent whitening agents. Dyes 4a-d were applied to polyester fabric and their performance was evaluated by means of measuring the degree of whiteness, the degree of brightness, color values, and reflectance spectrum in comparison with a standard fluorescent whitening agent, Hostalux ESR. Interestingly our synthesized optical whitener, 4a showed pronounced enhancement in the whitening properties over the Hostalux ESR. [ABSTRACT FROM AUTHOR]