Synthesis Of Chromones Research Articles

One-Pot Synthesis of Chromone-2-carboxylate Scaffold: An Important Pharmacophore with Diverse Biological Properties.

Chromone-2-carboxylate scaffold is growing as an important pharmacophore in medicinal chemistry with diverse biological properties. We have developed a facile one-pot transformation of 2-fluoroacetophenone directly to chromone-2-carboxylate scaffold in a single step via a tandem C-C and C-O bond formation. The majority of the previously reported medicinal chemistry synthetic protocols primarily used only one procedure which follows a two-step strategy that needs to start with "2-hydroxyacetophenone". Our methodology not only serves as an alternative one-pot methodology but also allows chemists to start from different raw materials (2-fluoroacetophenone) other than the traditional ortho-hydroxyacetophenone for maintaining the regioselectivity in the cyclization step. We further demonstrated the utility of our protocol by successfully extending the application to the synthesis of two natural products (Halenic acids A and B), various bis-chromones including drug molecules (DSCG, cromoglicic acid), and potent anti-Alzheimer compound (F-cromolyn). This methodology can serve as a promising alternative tool for finding new bioactive chromones with diverse modifications due to the opportunity to use new raw materials in the synthesis of chromones.

One-Pot Synthesis and Evaluation of Antioxidative Stress and Anticancer Properties of an Active Chromone Derivative.

Chromones are the structural building blocks of several natural flavonoids. The synthesis of chromones, which contain a hydroxy group on the ring, presents some challenges. We used the one-pot method to synthesize ten chromone derivatives and two related compounds using modified Baker-Venkataraman reactions. The structures were confirmed using FT-IR, 1H NMR, 13C NMR, and HRMS. The in vitro antioxidant assay revealed that compounds 2e, 2f, 2j, and 3i had potent antioxidant activity and that all these synthesized compounds, except those containing nitro groups, were harmless to normal cells. In addition, compounds 2b, 2d, 2e, 2f, 2g, 2i, and 2j had anticancer activity. Compounds 2f and 2j were used to investigate the mechanism of anticancer activity. Both 2f and 2j induced a slightly early apoptotic effect but significantly impacted the S phase in the cell cycle. The effect on cell invasion indicates that both compounds significantly inhibited the growth of cervical cancer cells. A chromone scaffold possesses effective chemoprotective and antioxidant properties, making it a promising candidate for antioxidant and future cancer treatments.

C3‐Functionalized Chromones Synthesis by Tandem C−H Elaboration and Chromone Annulation of Enaminones

AbstractChromone is a heterocyclic entity presents in a number of natural products, clinical pharmaceuticals, as well as molecules with enriched biological functions. As cutting‐edge area, the synthesis of chromones has seen spectacular progress over the past decade. Among the available synthetic modes toward chromone scaffolds, the annulation of ortho‐hydroxyphenyl functionalized N,N‐disubstituted enaminones has turned out to be one of the most reliable and practical ones. By combining this annulation with the featured transformation of the vinyl α‐C−H bond in the enaminone structure, a large number of tandem reactions providing structurally diverse chromones with C3‐functionalization have been recently realized. As a practical strategy in the synthesis of valuable heterocyclic molecules and an important branch in the enaminone‐based organic synthesis, such synthetic reactions are highly instructive for organic chemistry and many other disciplines related to this heterocyclic moiety. Herein, we present for the first time the research advances on the synthesis of C3‐functionalized chromones via tandem vinyl C−H bond elaboration and chromone annulation of ortho‐hydroxyphenyl functionalized tertiary enaminones.

Synthesis of chromones, annulated with oxygen-containing heterocycles with two hetero atoms at C(7)-C(8) bond

The present review represented the advanced synthetic strategies for chromones annulated at the C(7)-C(8) bond with five-membered, six-membered, and seven-membered oxygen-containing heterocycles with two heteroatoms, such as 6H-[1,3]dioxolo[4,5-h]chromen-6-one, 2,3-dihydro-7H-[1,4]dioxino[2,3-h]chromen-7-one, 3,4-dihydro-2H,8H-[1,4]dioxepino[2,3-h]chromen-8-one, 2,3-dihydro-1H,7H-chromeno[7,8-b][1,4]oxazin-7-one, 4H,12H-pyrano[2,3-a]phenoxazine-4-one and 9,10-dihydro-4H,8H-chromeno[8,7-e][1,3]oxazin-4-one. The biological activity of naturally occurring and modified synthetic fused hetarenochromones has been also highlighted.

Synthesis of Chromones from 1,1-Diacylcyclopropanes: Toward the Synthesis of Bromophycoic Acid E.

A tandem deprotection-cyclization reaction of 1,1-diacylcyclopropanes is described which allows rapid access to structurally diverse 2,3-disubstituted chromones in good yields, and with straightforward purification. The utility of this reaction is showcased by the construction of the potent antibacterial marine natural product bromophycoic acid E scaffold.

ChemInform Abstract: Synthesis of Chromones and Their Applications During the Last Ten Years

AbstractReview: 150 refs.

Synthesis of Chromone, Quinolone, and Benzoxazinone Sulfonamide Nucleosides as Conformationally Constrained Inhibitors of Adenylating Enzymes Required for Siderophore Biosynthesis

MbtA catalyzes the first committed step of mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) and is responsible for the incorporation of salicylic acid into the mycobactin siderophores. 5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS) is an extremely potent nucleoside inhibitor of MbtA that possesses excellent activity against whole-cell Mtb but suffers from poor bioavailability. In an effort to improve the bioavailability, we have designed four conformationally constrained analogues of Sal-AMS that remove two rotatable bonds and the ionized sulfamate group on the basis of computational and structural studies. Herein we describe the synthesis, biochemical, and microbiological evaluation of chromone-, quinolone-, and benzoxazinone-3-sulfonamide derivatives of Sal-AMS. We developed new chemistry to assemble these three heterocycles from common β-ketosulfonamide intermediates. The synthesis of the chromone- and quinolone-3-sulfonamide intermediates features formylation of a β-ketosulfonamide employing dimethylformamide dimethyl acetal to afford an enaminone that can react intramolecularly with a phenol or intermolecularly with a primary amine via addition-elimination reaction(s). The benzoxazinone-3-sulfonamide was prepared by nitrosation of a β-ketosulfonamide followed by intramolecular nucleophilic aromatic substitution. Mitsunobu coupling of these bicyclic sulfonamides with a protected adenosine derivative followed by global deprotection provides a concise synthesis of the respective inhibitors.

Synthesis of Chromones from 2,3-Allenoic Acids and Benzynes

A synthesis of chromones from the reaction of 2,3-allenoic acids with Kobayashi benzyne precursors (Y. Himeshima, T. Sonoda, H. Kobayashi Chem. Lett. 1983, 1211; Kobayashi was first to generate benzynes from ortho-TMS arylOTf) is presented. The reaction proceeds smoothly under mild conditions to afford chro­mone products in moderate to good yields; however, the scope of the process was not well investigated. The process is proposed to involve carboxylate addition of the allenoic acid to the generated benzyne to give intermediate A, which instead of forming a coumarin by direct intramolecular Michael addition, undergoes rearrangement to form C via oxetane B opening, followed by intramolecular oxa-Michael addition and hydrolysis to afford the chromone.

ChemInform Abstract: N‐Heterocyclic Carbene Catalyzed Intramolecular Hydroacylation of Activated Alkynes: Synthesis of Chromones.

AbstractIntramolecular Stetter‐type hydroacylation of o‐(propargyloxy)benzaldehydes, e.g. (I), (III), (V) or (VII), is efficiently catalyzed by a commercially available thiazolium‐based carbene catalyst to give chromones in good yields.

N‐Heterocyclic Carbene Catalyzed Intramolecular Hydroacylation of Activated Alkynes: Synthesis of Chromones

AbstractAn organocatalytic intramolecular Stetter‐type hydroacylation reaction between an aldehyde and an activated alkyne has been developed. This study induces salicylaldehyde‐derived alkyne derivatives to assemble into a series of chromone derivatives using a catalytic amount of thiazolium‐based carbene catalyst.

ChemInform Abstract: A New Chromone and Flavone Synthesis and Its Utilization for the Synthesis of Potentially Antitumorigenic Polycyclic Chromones and Flavones.

A new synthesis of chromones and flavones based on the ortho-directed metalation of methoxymethyl aryl ethers with alkyllithium reagents is described. It entails reaction of the ortho-lithiated intermediates with a conjugated unsaturated aldehyde followed by oxidation of the allylic alcohol product with «periodinane» to yield an ortho-allylic ketone. The latter on heating in acetic acid undergoes loss of the methoxymethyl protecting group and cyclization to a chromanone (or flavanone, if a β-phenyl substituent is present). Dehydrogenation by treatment with pyrrolidone hydrotribromide (PHT) in dimethyl sulfoxide yields the corresponding chromones (or flavones). This synthetic approach appears general in its applicability

ChemInform Abstract: Synthesis of Chromones and 4‐Hydroxyquinolines Based on Uncatalyzed Condensations of 1‐Methoxy‐1,3‐bis(trimethylsilyloxy)‐1,3‐butadiene with 2‐Alkoxy‐ and 2‐Nitrobenzyl Chlorides and Related Reactions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of chromones and 4-hydroxyquinolines based on uncatalyzed condensations of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with 2-alkoxy- and 2-nitrobenzoyl chlorides and related reactions

The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with 2-methoxybenzoyl chlorides afforded 3,5-diketoesters which were transformed, by treatment with boron tribromide, into functionalized 2-hydroxychroman-4-ones or chromones. The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with 2-nitrobenzoyl chlorides and subsequent reduction of the nitro group afforded functionalized 4-hydroxyquinolines. Their tautomeric equilibrium was studied by NMR spectroscopy and by computational methods.

Behavior of o‐Hydroxyacetophenones Towards Action of POCl3/DMF (Vilsmeier Reagent) in the Presence of BF3×Et2O: A Novel Observation in the Synthesis of Chromones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Behaviour of o-hydroxyacetophenones towards action of POCI3/DMF (Vilsmeier reagent) in presence of BF3.Et20 : a novel observation in the synthesis of chromones

Behaviour of o-hydroxyacetophenones towards action of POCI3/DMF (Vilsmeier reagent) in presence of BF3.Et20 : a novel observation in the synthesis of chromones

A new class of nonsteroidal aromatase inhibitors: design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17 alpha-hydroxylase/C17,20-lyase.

Aromatase (P450arom) is a target of pharmacological interest for the treatment of breast cancer. In this paper, we report the design, synthesis, and in vitro biological evaluation of a series of new (di)benzopyranone-based inhibitors of this enzyme. The design of the new compounds was guided by a CoMFA model previously developed for a series of nonsteroidal aromatase inhibitors. Both the chromone and the xanthone nuclei were taken as molecular skeletons, and the functions supposed to be critical for binding to the aromatase active site - a heterocyclic ring (imidazole or 1,3,4-triazole) linked to the aromatic moiety by a methylene unit and an H-bond accepting function (CN, NO(2), Br) located on the aromatic ring at a suitable distance from the heterocyclic nitrogen carrying the lone pair--were attached to them. The chromone, xanthone, and flavone derivatives were prepared by conventional synthetic methods from the appropriate methyl analogues. Aromatase inhibitory activities were determined by the method of Thompson and Siiteri, using human placental microsomes and [1 beta,2 beta-(3)H]testosterone as the labeled substrate. All the compounds were also tested on 17 alpha-hydroxylase/C17,20-lyase (P450 17), an enzyme of therapeutic interest for the treatment of prostatic diseases. The goal to find new potent inhibitors of aromatase was reached with the xanthone derivatives 22d,e (IC(50) values 43 and 40 nM, respectively), which exceeded the potency of the known reference drug fadrozole and also showed high selectivity with respect to P450 17. Moreover, compounds 22g-i based on the same xanthonic nucleus showed fairly high potency as P450 17 inhibitors (IC(50) values 220, 130, and 42 nM, respectively). Thus, they might be new leads for the development of drug candidates for androgen-dependent diseases.

Heterocyclic Synthesis With Nitriles: Synthesis Of Some New Chromone and Flavone and Its Utilization For The Synthesis Of Potentially Antitumorigenic Polycyclic Chromones and Flavones

A new synthesis of chromones and flavones based on the reaction of 2-hydroxy-1-acetonaphthone (1) with cinammonitriles (2 a-h) is described. Structures of the compounds are established by chemical and spectral data. This synthetic approach appears general in its applicability. It has been applied to the synthesis of a series of polycyclic chromone and flavone compounds containing the naphthalene and pyrene ring systems that hold promise as agents for the chemo preventation of cancer.

Oxidation of Chromanones and 2-Spirochromanones with [Hydroxy(tosyloxy)iodo]benzene in Acetonitrile Under Reflux as well as Ultrasound: A Convenient Route for the Synthesis of Chromones, Tetrahydroxanthones, and Their Higher Homologues

Abstract Oxidation of chromanones (1a-i) and 2-spiro-chromanones (j-m) using [hydroxy(tosyloxy)iodo] benzene in refluxing acetonitrile as well as using ultrasound via dehydrogenation and 2,3-alkyl migration provides a convenient route for the synthesis of chromones (2a-i), tetrahydroxanthones (2j,k) and their higher homologues (21,m). The ultrasound also enhances substantially the rate of above transformations.

Syntheses of chromones and quinolones via pd-catalyzed carbonylation of o-iodophenols and anilines in the presence of acetylenes

Synthesis of 2-substituted chromones and quinolones has been performed by a Pd-catalyzed carbonylation of o-iodophenols or o-iodoanilines in the presence of terminal acetylenes in a high yield through coupling of halides and acetylenes followed by cyclization as a one-pot reaction.

Mixed anhydride of acetic and formic acids in the synthesis of chromones

A study was carried out on the reaction of α-substituted 2-hydroxyacetophenones with the mixed anhydride of acetic and formic acids in the presence of bases of different strength. Chromones containing a conjugated electron-withdrawing substituent at C(3) are formed in close to quantitative yield in the presence of triethylamine. The preparation of chromones containing an unconjugated substituent under these conditions is recommended only for 5-hydroxy chromones.