Efficient one-pot synthesis of 1,3-diaryl-3H-benzo[f]chromenes using ferric hydrogensulfate

An efficient and easy method for one-pot three-component synthesis of l,3-disubstituted-3H-benzo[f]chromenes by the condensation of naphtol,aromatic aldehyde derivatives and phenylacetylene in the presence of ferric hydrogensulfate[Fe（HSO4）3], has been described.The catalyst displayed high activity which afforded the corresponding 1,3-disubstituted-3H-benzo[f]chromenes in satisfying yields.Alkyl-substituted phenols were examined and the corresponding benzopyran derivatives were synthesized in moderate yields.Heterogeneous nature of the using catalyst made it reusable for further chemical reactions.

In vitro Pharmacological Activity of Chromenes in Disk of Helianthus annuus

[Objectives]The anti-tumor,anti-bacterial,anti-acetylcholinesterase and anti-α-glucosidase activity in vitro of five chromenes isolated from Helianthus annuus disk was studied,in order to provide reference for the development and utilization of H.annuus disk resources.[Methods]The effect of different concentrations of chromenes on the survival rate of leukemia HL-60 cells,lung cancer A549 cells,liver cancer SMMC-7721 cells,breast cancer MCF-7 cells and colon cancer SW480 cells was detected by MTS method,and the IC50 was calculated.The inhibitory activity of chromenes against Escherichia coli,Staphylococcus aureus subsp.aureus,Salmonella enterica subsp.enterica,Pseudomonas aeruginosa and Candida albicans was detected by microdilution method.The DTNB substrate method was used to detect the inhibitory activity of chromenes on acetylcholine.The PNPG substrate method was used to detect the inhibitory activity of chromenes onα-glucosidase.[Results]The five chromenes had no obvious in vitro inhibitory activity on the five kinds of tumor cells,with IC50 greater than 40μM.The five chromenes had no obvious in vitro inhibitory activity against the four kinds of bacteria and C.albicans.The five chromenes had certain inhibitory activity on acetylcholinesterase,and among them,6-acetyl-2,2-dimethylchromene and 6-acetyl-7-hydroxy-2,3-dimethylchromene showed strong inhibitory activity on acetylcholinesterase,with IC50 of 28.253 and 16.945μM,respectively,both smaller than that(0.275μM)of the positive control tacrine(P<0.01).The five chromenes showed good inhibitory effect onα-glucosidase,and among them,7-hydroxy-6-hydroxyacetyl-2,2-dimethylchromene and 6-acetyl-7-hydroxy-2,3-dimethylchromene had stronger inhibitory activity,with IC50 of 20.240 and 21.052μM,respectively,significantly better than that(169.780μM)of the positive control acarbose(P<0.01).[Conclusions]The five chromenes in H.annuus disk have certain in vitro inhibitory activity against acetylcholinesterase andα-glucosidase and certain potential in fighting neurodegenerative diseases and diabetes.

CuO nanoparticles:An efficient and recyclable nanocatalyst for the rapid and green synthesis of 3,4-dihydropyrano[c]chromenes

Copper oxide nanoparticles showed excellent catalytic activity through three-component condensation reaction of aldehydes, malononitrile,and 4-hydroxycoumarin for the synthesis of 3,4-dihyropyrano[c]chromenes in water medium in excellent yields and very short reaction times.

Design, Synthesis and Biological Evaluation of 2-Aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]chromen Derivatives as a Novel Series of Estrogen Receptor Modulators

Based on the principles of the bioisosterism, combination of the active substructures of selective estrogen receptor modulators which are currently therapeutic agents available for the prevention and treatment of various estrogen dependent diseases, and structural optimization, a novel series of 2-aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]- chromen derivatives was designed as potent selective estrogen receptor modulators via molecular docking. The target compounds have been synthesized, and characterized by 1R, proton NMR, ESI-MS, elemental analysis and evaluated for their antitumor activity against human osteosarcoma U2OS-EGFP-4FI2G cell line. Some target compounds showed good inhibition effects on U2OS-EGFP-4F12G cell line and the preliminary structure-activity relationships were discussed.

Crystal Structure of 3-(4-Methoxyphenyl)-2-(4-methylbenzoyl)-6,7-dihydro-5H-furo[3,2-g]chromene

The crystal structure of 3-（4-methoxyphenyl）-2-（4-methylbenzoyl）-6,7-dihydro-5H-furo[3,2-g]chromene was obtained by X-ray single-crystal diffraction. The molecule is in the triclinic crystal system, space group P1 with a = 11.0745（4）, b = 13.0953（7）, c = 15.8773（8） ？, α = 92.811（4）, β = 104.815（4）, γ = 111.797（4）o, Z = 4, the final R = 0.0567 and w R = 0.1540. X-ray crystal structure data revealed that one asymmetric structure unit of the title compound contained two molecules. The existence of methyl group changed the dihedral angle between furan ring and the phenyl ring at the C2 position of the furo[3,2-g]chromene scaffold as well as the conformation, and had a further influence on the bioactivity of the furo[3,2-g]chromene derivatives.

Synthesis,Crystal Structure and Fluorescence of a Bicyclic Product Containing Chromene and Propargylamine Skeleton

The bicyclic product containing a chromene skeleton and a propargylamine skeleton（C（22）H（22）N2O2） was synthesized from the double sites of terminal alkyne, piperazine derivative and formaldehyde via one-pot procedure. Its structure was characterized by ^1H NMR, ^13C NMR, IR and H RMS, and further confirmed by single-crystal X-ray diffraction. It crystallizes in the monoclinic system, space group P21/n with a = 12.6571（14）, b = 11.3249（12）, c = 12.6571（14） A, β = 105.22°,V = 1750.6（3） A^3, Z = 4, R = 0.0568 and w R = 0.1444. The fluorescence of the product was discussed.

Synthesis and Crystal Structure of 5-Allyl-2,3-dihydro-9-(2-hydroxy-5-oxocyclopent-1-enyl)-cyclopenta[b]chromen-1(9H)-one Monohydrate

The title compound 5-allyl-2,3-dihydro-9-（2-hydroxy-5-oxocyclopent-1-enyl）-cyclopenta[b]chromen-1（9H）-one monohydrate（C20H18O4.H2O,Mr = 340.36） was synthesized and crystallized.It crystallizes in the triclinic system,space group P with a = 8.5840（17）,b = 8.7027（17）,c = 11.561（2）,α = 89.69（3）,β = 74.33（3）,γ = 86.13（3）°,V = 829.6（3）（A°）^3,Z = 2,Dc = 1.363 g/cm^3,MoKa radiation（λ = 0.71073 ）,F（000） = 360,μ = 0.098 mm^-1,the final R = 0.0430 and wR = 0.1008 for 2957 observed reflections with（I 〉 2σ（I））.X-ray analysis reveals that atoms C（1）,C（2）,C（3）,C（4）,C（5） and O（1） on the new pyran ring are coplanar,which is obviously different from the half-chair or boat conformations of other similar compounds.

Synthesis and Crystal Structure of 9-Amino-7-(2-chlorophenyl)-6H-benzo[c]thiochromene-8,8,10(7H)-tricarbonitrile DMF Solvate

The title compound 9-amino-7-（2-chlorophenyl）-6H-benzo[c]thiochromene-8,8,10（7H）-tricarbonitrile DMF solvate（C25H20ClN5OS,Mr = 473.97） was synthesized and crystallized.The crystal belongs to triclinic,space group P1 with a = 7.6393（2）,b = 10.5212（3）,c = 15.0573（4） ,α = 86.797（1）,β = 79.445（1）,γ = 75.379（1）°,Z = 2,V = 1151.16（5） 3,Dc = 1.367 g.cm-3,μ（MoKα） = 0.285 mm-1,F（000） = 492,R = 0.0389 and wR = 0.1005 for 3455 observed reflections（I 2σ（I））.X-ray analysis reveals that the new six-numbered ring（C（1）-C（6）） forms a skew boat conformation.The molecule links a molecule of DMF via the N（1）-H（1A）...O（1） hydrogen bond,while another hydrogen bond C（23）-H（23A）...N（2） links adjacent molecules,forming dimmers along the a axis.

Synthesis and Antimicrobial Activity of Heterocyclic Compounds Containing Chromene Ring

Synthesis of some new compounds containing chromene ring are described in this work. They were synthesized in moderate to good yield, started with Condensation of 7-hydroxy-4-methylcoumarin （1） with ethyl bromoacetate furnishes ethyl-2-（4-methyl-2-oxo-2H-chromen-7-yloxy） acetate （2）. The structures of all the new compounds were confirmed using IR, 1H-NMR spectra and micro analysis, selected members of the synthesized compound were screened for antimicrobial activity. They have shown a wide range of activity from one completely inactive compound to medium active ones.

Multimodal 4-arylchromene derivatives with microtubule-destabilizing,anti-angiogenic,and MYB-inhibitory activities

Aim:Efficient and readily available anticancer drugs are sought as treatment options.For this reason,chromene derivatives were prepared using the one-pot reaction and tested for their anticancer and anti-angiogenic properties.Methods:2-Amino-3-cyano-4-(aryl)-7-methoxy-4H-chromene compounds(2A-R)were repurposed or newly synthesized via a three-component reaction of 3-methoxyphenol,various aryl aldehydes,and malononitrile.We performed assays to study the inhibition of tumor cell growth[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromid(MTT)assay],effects on microtubules(immunofluorescence),cell cycle(flow-activated cell sorting analysis),angiogenesis(zebrafish model),and MYB activity(luciferase reporter assay).Fluorescence microscopy was applied for localization studies via copper-catalyzed azide-alkyne click reaction of an alkyne-tagged drug derivative.Results:Compounds 2A-C and 2F exhibited robust antiproliferative activities against several human cancer cell lines(50%inhibitory concentrations in the low nanomolar range)and showed potent MYB inhibition.The alkyne derivative 3 was localized in the cytoplasm after only 10 min of incubation.Substantial microtubule disruption and G2/M cell-cycle arrest were observed,where compound 2F stood out as a promising microtubule-disrupting agent.The study of anti-angiogenic properties showed that 2A was the only candidate with a high potential to inhibit blood vessel formation in vivo.Conclusion:The close interplay of various mechanisms,including cell-cycle arrest,MYB inhibition,and anti-angiogenic activity,led to identifying promising multimodal anticancer drug candidates.

A convenient one-pot synthesis of new chromeno[3,4-c]chromene and chromeno[3,4-c]pyridine derivatives in the presence of high surface area of magnesium oxide

In this investigation a new strategy involves the one-pot, three-component reaction of malononitrile, salycilaldehyde and phenol derivatives in the presence of high surface area of MgO is extended to the formation of chromeno[3,4-c]ehromene derivatives in good to excellent yields in a short reaction time. Also, the three component reactions of an aldehyde such as salycilaldehyde and ketones with malononitril for the formation of chromeno[3,4-c]pyridines are investigated.

Aqueous-mediated Michael Addition of Active Methylene Compounds with Nitroalkenes

A simple, atom economical and highly efficient green protocol has been developed for the synthesis of Michael adducts of nitroalkenes and 2-amino-2-chromene derivatives by Michael addition of active methylene compounds （such as malononitrile and ethyl cyanoacetate） to nitroalkenes under aqueous-mediated conditions. This green approach provided the desired products in high yields and the reaction scope proved to be quite broad.

Morpholine Catalyzed One-pot Multicomponent Synthesis of Compounds Containing Chromene Core in Water

A series of dihydropyrano[c]chromene was obtained via condensation of aldehyde, malononitrile and 4-hydroxycoumarin in water catalyzed by morpholine, as a one-pot reaction. The significance of our findings relates to reducing the use of organic solvents, potentially toxic and hazardous materials, as well as its simplicity, good yields, mild conditions, and lower costs.

Three-component reaction for synthesis of functionalized spiro[indoline-3,4'-pyrano[3,2-h]quinolines]

The functionalized spiro[indoline-3,40-pyrano[3,2-h]quinolines] were efficiently prepared in high yields from three-component reaction of 8-hydroxyquinoline, isatins and malononitrile or ethyl cyanoacetate in ethanol at room temperature for about 12 h in the presence of piperidine.

Iodine catalyzed synthesis of the chromene derivatives in one-pot

Iodine catalyzed one-pot reactions of salicylaldehyde and dimolecular 1H-indene-l,3（2H）-dione, barbituric acids, 4-hydro- xycoumarin, or 4-hydroxy-6-methylpyran-2-one were performed and provided a rapid, convenient and general approach to synthesize the chromene derivatives. 2-（11-Oxo-10,11-dihydroindeno[1,2-b]chromen-10-yl）-lH-indene-1,3（2H）-diones P1-P4 and 10-（4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl）-3-methylpyrano[4,3-b]chromen-1（1OH）-ones P8-P9 were unprecedentedly prepared and structurally identified by NMR and Mass. The confirmation of structure by single crystal X-ray crystallography is reported for P3.

Efficient synthesis of chromenopyridine and chromene via MCRs

MCRs for preparation of chromenopyridines under reflux conditions and chromenes at room temperature conditions from different salicylaldehydes,malononitrile and different thiols（mol ratio- 1：2：1） were established.Mechanistic investigation suggests that the MCRs undergo different pathways at different temperatures and catalyzed by different organic bases.The structure of chromenopyridine and chromene are confirmed by crystal X-ray crystallography.

One-pot Sequential Reaction for the Synthesis of Polysubstituted 3-（3-Nitro-2-phenylchroman-4-yl）-3-arylaminoacrylates

The one-pot sequential reaction of arylamines, methyl propiolate and 2-aryl-3-nitrochromenes without any catalyst in refluxing ethanol afforded the polysubstituted 3-（3-nitro-2-phenylchroman-4-yl）-3-arylaminoacrylates in good yields and with high diastereoselectivity. Reaction mechanism was believed involving the initial formation of β-enamino ester and sequential Michael addition.

First example of multicomponent synthesis of 1-ethoxy-3-(4-aryl)-1-phenyl- 1H-benzo[f]-chromene derivatives

A new series of 1-ethoxy-3-（4-aryl）-1-phenyl-1H-benzo[f]chromenes have been synthesized efficiently.The procedure involves the multicomponent reaction of 2-naphthol,acetophenone derivatives,and triethyl orthobenzoate catalyzing by efficient bis（2-anilinotropone） Ti complex.