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A GaCl3‐catalyzed [3 + 2]‐cycloaddition/intramolecular esterification cascade of donor–acceptor cyclopropane‐1,1‐diesters with salicylaldehydes has been reported. A wide range of tetrahydro‐4H‐furo[3,2‐c]chromen‐4‐ones have been efficiently delivered in moderate to good yields. Mechanistic studies suggest that the reaction involves the [3 + 2]‐cycloaddition followed by intramolecular esterification to access 4H‐furo[3,2‐c]chromenones. [ABSTRACT FROM AUTHOR]

Several N‐ethoxycarbonylmethyl enaminones, prepared by Eschenmoser sulfide contraction between N‐(ethoxycarbonylmethyl)pyrrolidine‐2‐thione and various ortho‐oxygenated phenacyl halides, underwent cyclisation to give ethyl 6‐aryl‐2,3‐dihydro‐1H‐pyrrolizine‐5‐carboxylates upon microwave heating with silica gel in xylene. With enaminones made from ortho‐hydroxyphenacyl halides, not only did dihydropyrrolizine formation take place, but spontaneous lactonisation also occurred to give 9,10‐dihydrochromeno[4,3‐b]pyrrolizin‐6(8H)‐ones. Bromination and Suzuki‐Miyaura arylation of these chromenopyrrolizines at the free C−H site on the pyrrole ring afforded four analogues of the lamellarin alkaloids in which a pyrrolidine ring replaces the isoquinoline system in the fused polycyclic core. The product 11‐(3,4‐dimethoxyphenyl)‐2,3‐dimethoxy‐9,10‐dihydrochromeno[4,3‐b]pyrrolizin‐6(8H)‐one, in particular, is a congener of the well‐known lamellarin G trimethyl ether. Preliminary results pertaining to an extension to chromenone‐fused indolizines are also reported. [ABSTRACT FROM AUTHOR]

The preparative utility of the pyrolysis of acetylenic compounds is demonstrated in the flash vacuum pyrolysis of some propargyl ethers, amines and an ester that has resulted in interesting furans, indanones, quinoline, and chromenones as major products. The products of the pyrolysis of each substrate were analyzed, identified, characterized, and compared. [ABSTRACT FROM AUTHOR]

Unprecedented catalyst‐free synthesis of chromen‐4‐ones and bezothiophen‐3‐ones via insertion of in situ prepared benzyne intermediate into masked enal and masked mercapto acid is reported herein. The envisaged methodology does not need any catalyst and involves cycloaddition of benzyne, formed in situ, with 2,2,6‐trimethyl‐1,3‐dioxin‐4‐one and 2‐methyl‐2‐phenyl‐1,3‐oxathiolan‐5‐one to afford the target chromen‐4‐ones (75–89 %) and benzothiophen‐3‐ones (69–86 %) respectively. [ABSTRACT FROM AUTHOR]

Abstract To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a new series of 1,2,3-triazole-chromenone derivatives were designed and synthesized based on the multi target-directed ligands approach. The in vitro biological activities included acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition as well as anti-Aβ aggregation, neuroprotective effects, and metal-chelating properties. The results indicated a highly selective BuChE inhibitory activity with an IC50 value of 21.71 μM for compound 10h as the most potent compound. Besides, compound 10h could inhibit self-induced Aβ1–42 aggregation and AChE-induced Aβ aggregation with 32.6% and 29.4% inhibition values, respectively. The Lineweaver–Burk plot and molecular modeling study showed that compound 10h targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of BuChE. It should be noted that compound 10h was able to chelate biometals. Thus, the designed scaffold could be considered as multifunctional agents in AD drug discovery developments.

The present paper describes a facile entry to various substituted 7,8-dihydro-2H-chromen-5- ones under neat conditions using simple carbonized sugar as a catalyst. The reaction was promoted by visible light under neat or in acetic acid as a solvent with a catalyst to afford the desired products in good to excellent yield. Mild conditions coupled with ease of operation make the protocol synthetically attractive and may find widespread application for the synthesis of chromenone scaffold. [ABSTRACT FROM AUTHOR]

Abstract A convenient and improved method for the synthesis of beta acids or lupulones, which are known to possess e. g. anti‐cancer, anti‐inflammatory, anti‐oxidative and antimicrobial activity, has been developed successfully. Further derivatization of these complex structures to the corresponding dihydrochromen‐7‐ones, including the natural product machuone, was realized to simplify their analysis and to confirm their molecular structure. In addition to practical and safe laboratory procedures, the advantages associated with this new approach involve the use of water as a solvent and the direct crystallization of lupunones from acetonitrile, rendering our strategy more efficient and benign as compared to available methods.

Four new chromones, phomochromenones D–G (1–4), along with four known analogues, diaporchromone A (5), diaporchromanone C (6), diaporchromanone D (7), and phomochromenone C (8), were isolated from the culture of Phomopsis asparagi DHS-48 from Chinese mangrove Rhizophora mangle. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1 and 4 were assigned on the basis of experimental and calculated electronic circular dichroism (ECD) data, and those of enantiomers 2 and 3 were determined by a modified Mosher’s method and basic hydrolysis. To the best of our knowledge, phomochromenones D–F (1–4) possessing a 3-substituted-chroman-4-one skeleton are rarely found in natural sources. Diaporchromone A (5) showed moderate to weak immunosuppressive activity against T and/or B lymphocyte cells with IC50 of 34 μM and 117 μM.

An efficient one pot four component strategy has been developed for the synthesis of highly substituted fluoro chromenone derivatives (5 a‐p) in good yields from β‐aryl thio acetanilide, aldehydes, cyclic 1,3‐diketones and NFSI (N‐Fluorobenzenesulfonimide) in presence of water. The fluoro imino chromenone intermediate 6 is isolated under the inert condition in high yield. [ABSTRACT FROM AUTHOR]

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5- g ]chromenones were synthesized featuring phenyl and chalcone bridge representing flavones or homoisoflavonoids and in vitro antioxidant and anticancer properties were investigated. • [1,3]dioxolo[4,5-g]chromenones were inspected for pharmacological properties. • Presence of EWD and ED substituents displayed varied and promising IC50 data. • OCF 3 and OCH 3 played a crucial role against DPPH, ABTS +, SK-OV-3 and HT-29. • Halogen atom(s) attributed excellent inhibitory potential against HeLa and A-549. • Promising activities warrant further studies for the structural optimization. Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5- g ]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS + and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF 3) and j , k (OCH 3) were found to play a crucial role scavenging DPPH and ABTS + as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN) were carried out to confirm the final structures. [ABSTRACT FROM AUTHOR]

A convenient and improved method for the synthesis of beta acids or lupulones, which are known to possess e. g. anti‐cancer, anti‐inflammatory, anti‐oxidative and antimicrobial activity, has been developed successfully. Further derivatization of these complex structures to the corresponding dihydrochromen‐7‐ones, including the natural product machuone, was realized to simplify their analysis and to confirm their molecular structure. In addition to practical and safe laboratory procedures, the advantages associated with this new approach involve the use of water as a solvent and the direct crystallization of lupunones from acetonitrile, rendering our strategy more efficient and benign as compared to available methods. [ABSTRACT FROM AUTHOR]

An N‐heterocyclic carbene catalyzed domino sequence via α,β‐unsaturated acyl azolium intermediates has been developed. This strategy provides a convenient enantioselective route to functionalized tricyclic coumarin derivatives and cyclopentanes. DFT studies and control experiments were performed to gain better insight into the reaction mechanism. Via acyl azoliums: A quadruple domino sequence proceeding via α,β‐unsaturated acyl azolium intermediates is catalyzed by an N‐heterocyclic carbene. This strategy provides a convenient direct route to functionalized tricyclic chromenone derivatives and cyclopentanes. DFT studies and control experiments provide insight into the reaction mechanism. [ABSTRACT FROM AUTHOR]

An efficient synthesis of 4H-chromene-4-ones via enamino ketones, with cyclization by using T3P® under microwave heating is described. This is the first report for the synthesis of chromones by using T3P®. Significant features of this method include short reaction times and high-purity products. [ABSTRACT FROM AUTHOR]

Four ( 1, 2, 4 and 6) synthetic quaternary ammonium derivatives of pyranochromenones and (coumarinyloxy)acetamides were synthesized and investigated for their antimicrobial efficacy on MRSA (Methicillin-resistant Staphylococcus aureus), and multi-drug resistant Pseudomonas aeruginosa, Salmonella enteritidis and Mycobacterium tuberculosis H37Rv strain. One of the four compounds screened i.e. N, N, N-triethyl-10-((4,8,8-trimethyl-2-oxo-2,6,7,8-tetrahydropyrano[3,2- g]chromen-10-yl)oxy)decan-1-aminium bromide ( 1), demonstrated significant activity against S. aureus, P. aeruginosa and M. tuberculosis with MIC value of 16, 35, and 15.62 µg/ml respectively. The cytotoxicity evaluation of compound 1 on A549 cell lines showed it to be a safe antimicrobial molecule, TEM study suggested that the compound led to the rupture of the bacterial cell walls. [ABSTRACT FROM AUTHOR]

Synthesis and flash vacuum pyrolysis (FVP) of acetylenic esters and ethers of paracetamol and aspirin and their analogues were performed. The products were analyzed, identified, and characterized. Acetylenic esters and ethers of paracetamol resulted in benzofuran, and cyclohepta[ b ]pyrrol-2(1 H)-one. Aspirin and its derivatives produced chromenones, xanthones, indenones, chromenes, and other heterocyclic compounds. [Display omitted] • Synthesis and FVP of aspirinderivatives. • Synthesis and FVP of paracetamol derivatives and analogues. • Valuable routes for synthesis of xanthones and chromenones by FVP. [ABSTRACT FROM AUTHOR]

In this work, novel chromenones linked to 1,2,3-triazole ring system were synthesized and evaluated for their anti-ChE activity. Among them, N -((1-(2-chlorobenzyl)-1 H -1,2,3-triazol-5-yl)methyl)-8-methoxy-2-oxo-2 H -chromene-3-carboxamide ( 6m ) showed good anti-acetylcholinesterase activity (IC 50 = 15.42 μM). Also, compound 6m demonstrated neuroprotective effect against H 2 O 2 -induced cell death in PC12 neurons, however, it showed no beta-secretase (BACE1) inhibitory activity. Docking and kinetic studies separately confirmed dual binding activity of compound 6m since it targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. [ABSTRACT FROM AUTHOR]

Stabilized sulfur ylide mediated cyclopropanation and formal [4+1] cycloaddition of 3-acyl-2 H-chromenones and their imines were explored. The transformations could be performed under mild conditions and were shown to have wide substrate scopes and significant functional-group tolerance; furthermore, the reactions proceeded with excellent regioselectivity. Thus, they are powerful methods for the one-pot synthesis of highly functionalized cyclopropane- and dihydropyrrole-fused chromen-2-one derivatives. [ABSTRACT FROM AUTHOR]

This work describes synthesis of novel chromenone derivatives bearing 4-nitrophenoxy phenyl acryloyl moiety through the reaction of 4-(4-nitrophenoxy)benzaldehydes and 3-acetyl-2 H-chromen-2-ones in refluxing toluene. Cytotoxicity of all compounds was evaluated using a tetrazolium (MTT) colorimetric assay against human breast cancer cell line, MDA-MB-231. [ABSTRACT FROM AUTHOR]

Examples of hydroxymethylated analogues of heteroaryl cores such as quinazolin-4-ones, isoquinolin-1(2H)-ones, pyrido[3,4- d]pyrimidin-4(3H)-ones, chromen-4-ones and pyrrolo[2,1-f][1,2,4]triazin- 4(3H)-ones are sparse or non-existent in the scientific literature. We have demonstrated that such compounds are accessible by using standard procedures from readily available raw materials. [ABSTRACT FROM AUTHOR]

An efficient Stork-Danheiser sequence has been developed for the preparation of a variety of 3-alkynyl-2-(hydroxymethyl)cyclohex- 2-en-1-ones in good to excellent yields from the corresponding 4,6,7,8-tetrahydro-5H-1,3-benzodioxin-5-ones and terminal alkynes. Several of the 3-alkynyl-2-(hydroxymethyl)cyclohex-2-en-1-one products were catalytically cyclized to give the corresponding 3-aryl- 1,5,6,7-tetrahydro-8H-isochromen-8-ones. [ABSTRACT FROM AUTHOR]

Cute CO! An interesting and straightforward procedure for the carbonylative synthesis of chromenones from readily available salicylic aldehydes and benzyl chlorides has been developed (see scheme; DPPP=1,3‐bis(diphenylphosphino)propane). In the presence of a palladium catalyst, various coumarins were produced in good to excellent yields. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hydrazine promotes ANRORC reaction in 2-(trifluoromethyl)-2H-chromen-5(6H)-ones. [•] New series of 2-[(1H-pyrazol-4-yl)arylmethyl]-cyclohex-2-en-1-ones is synthesized. [•] The respective ANRORC reaction type mechanism is presented and discussed. [•] Structures solved by MS, X-ray, DFT calculations and 1H, 13C and 19F NMR data. [•] 19F NMR assignments the trifluoromethyl group position at pyrazolyl-cyclohexenones. [Copyright &y& Elsevier]

The four new sesquiterpenoids 1- 4, and the new 2-(2-phenylethyl)-4 H-chromen-4-one (=2-(2-phenylethyl)-4 H-1-benzopyran-4-one) derivative 5, together with the two known sesquiterpenoids 6 and 7, the five known chromenones 8- 12, and 1-hydroxy-1,5-diphenylpentan-3-one ( 13), were isolated from a 70% MeOH extract of Aquilaria malaccensis agarwood chips. Their structures were elucidated on the basis of comprehensive spectral analyses and comparison with literature data. [ABSTRACT FROM AUTHOR]

A series of novel ammonium derivatives were synthesized and examined for their antimicrobial efficacy. Comparison of antimicrobial spectrum revealed that compounds 9, 11, 16 and 23 had strong potential against pathogens in vitro. Cytotoxicity results showed compound 9 to be least toxic, it is non-toxic to A549 and U87 cells in MTT assay and exhibits marginal toxicity (15-20%) to human erythrocytes at a concentration of 1000 μg/ml as compared to 100% lysis of cells by 31.25 μg/ml of the standard drug amphotericin B. This compound has MIC values in the range of 1.95-31.25 μg/disc in DDA against different pathogens and may considered to be an important lead antimicrobial molecule for further exploration. [ABSTRACT FROM AUTHOR]

Abstract: The molecular structure, packing properties, and intermolecular interactions of a series of pyrrole derivatives have been determined by single-crystal X-ray diffraction. They were efficiently synthesized from mesoionic oxazoles and selected chromenones via initial 1,3-dipolar cycloaddition followed by cascade transformations. Compounds 4–6 are described as three fused rings associated in the crystal lattice through H-bonding interactions. Besides the H-bonding interactions encountered in the crystal packing of 4–8, a different strong centrosymmetric π-interaction has been found in 8, involving the cyano group and the π-system of aromatic pyrrole ring. A density functional theory (DFT) study was carried out on the supramolecular dimer in order to understand the nature and role of this intermolecular force in driving the molecular packing. [Copyright &y& Elsevier]

Abstract: The one-pot, simple and efficient three-component condensation protocol for the preparation of a series of twenty-five new 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones, where aryl=Ph, 4-tolyl, 4-ClPh, 4-NO2Ph and 4-CHOPh, and acyl=Ac, Bz, 4-FBz, furan-2-oyl, thien-2-oyl and naphth-1-oyl, employing 1,3-cyclohexanedione, five aryl aldehydes and for the first time, six 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluoroalk-3-en-2-ones, is described. Yields in 15–75% were obtained when the MCRs were performed in the presence of a catalytic amount of triethylamine (25mol%) and in ethanol as solvent under reflux for 16h. A representative X-ray diffraction data for 3-acetyl-4-phenyl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one is also showed. [Copyright &y& Elsevier]

Abstract: The synthesis and biological evaluation of libraries of 8-biarylchromen-4-ones enabled the elucidation of structure–activity relationships for inhibition of the DNA-dependent protein kinase (DNA-PK), with 8-(3-(thiophen-2-yl)phenyl)chromen-4-one and 8-(3-(thiophen-3-yl)phenyl)chromen-4-one being especially potent inhibitors. [Copyright &y& Elsevier]

Four new chromones, phomochromenones D–G (1–4), along with four known analogues, diaporchromone A (5), diaporchromanone C (6), diaporchromanone D (7), and phomochromenone C (8), were isolated from the culture of Phomopsis asparagi DHS-48 from Chinese mangrove Rhizophora mangle. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1 and 4 were assigned on the basis of experimental and calculated electronic circular dichroism (ECD) data, and those of enantiomers 2 and 3 were determined by a modified Mosher's method and basic hydrolysis. To the best of our knowledge, phomochromenones D–F (1–4) possessing a 3-substituted-chroman-4-one skeleton are rarely found in natural sources. Diaporchromone A (5) showed moderate to weak immunosuppressive activity against T and/or B lymphocyte cells with IC50 of 34 μM and 117 μM. [ABSTRACT FROM AUTHOR]

To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a new series of 1,2,3-triazole-chromenone derivatives were designed and synthesized based on the multi target-directed ligands approach. The in vitro biological activities included acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition as well as anti-Aβ aggregation, neuroprotective effects, and metal-chelating properties. The results indicated a highly selective BuChE inhibitory activity with an IC50 value of 21.71 μM for compound 10h as the most potent compound. Besides, compound 10h could inhibit self-induced Aβ1–42 aggregation and AChE-induced Aβ aggregation with 32.6% and 29.4% inhibition values, respectively. The Lineweaver–Burk plot and molecular modeling study showed that compound 10h targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of BuChE. It should be noted that compound 10h was able to chelate biometals. Thus, the designed scaffold could be considered as multifunctional agents in AD drug discovery developments. [ABSTRACT FROM AUTHOR]

By introducing a disposable activating substituent at C-3, the asymmetric 1,4-addition to a notoriously unreactive 2-substituted chromenone was achieved with high levels of (2R)-stereoselectivity in the presence of a chiral Cu(I)-phosphoramidite complex as a catalyst. This paved the way for an efficient and conceptually novel synthesis of (R,R,R)-α-tocopherol from readily available starting materials., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)