Iodide-Catalyzed Selenium-Assisted Sequential Multicomponent Synthesis of a Luminescence Benzo-Oxazino-Isoindole Framework.

We have described an unexpected pathway using the R-NC/Se system for the synthesis of the unreported benzo-oxazino-isoindole framework by the iodide-catalyzed selenium-assisted sequential multicomponent reaction of the Knoevenagel adduct of ninhydrin and malononitrile, isocyanide, amine, and elemental selenium under mild reaction conditions. The photophysical properties of the products were investigated by absorption and emission spectroscopy, revealing that the new heterocyclic system has good fluorescence properties.

Isocyanide Insertion-Cyclization Reaction for Imidazoisoindol-5-imine Scaffold Synthesis: A Selective Solvatochromic Fluorescent Probe for Methanol Detection.

An efficient, ligand-free, and Pd-catalyzed method for the synthesis of imidazoisoindole imine scaffolds with satisfactory yields via C-C and C-N bond formation has been developed. The synthesized scaffolds have unique potential for selective MeOH detection from other solvents, especially EtOH. The appealing features of this transformation are phosphinic ligand-free conditions, the use of a small amount of Pd(OAc)2, and a practical procedure for the synthesis of imidazoisoindole imine scaffolds.

Synthesis and evaluation of in vitro cytotoxic effects of triazol/spiroindolinequinazolinedione, triazol/indolin-3-thiosemicarbazone and triazol/thiazol-indolin-2-one conjugates.

PURPOSE: Cancer as one of the major diseases with high mortality rates threats human life in the world. Subsequently, the design new potent anticancer agents has attracted much attention in the area of synthetic and medicinal chemistry. In this study, new triazol-linked spiroindolinequinazolinone, thiazol-oxindole and oxindole-thiosemicarbazone conjugates were synthesized and evaluated for their in vitro cytotoxic activity toward different cancer lines. METHODS: Some new triazol-linked oxindoles and spirooxindoles conjugates were synthesized. The synthesized compounds were tested for their in vitro cytotoxic activity toward cancer lines including A375, PC3, LNCaP, MDA MB231 and normal cells HDF (human dermal fibroblast). RESULTS: Among all synthesized compounds, the triazol-linked oxindol-thiosemicarbazone conjugate 10b showed the highest cytotoxic activity against different cancer cells. By using quantitative real time PCR (qRT-PCR), it was found that 10b is able to induce apoptosis by alteration of Bax, Bcl2 balance (i.e. by up regulation of Bax and down regulation of Bcl-2 mRNA expression levels). The DAPI staining was used to show the death of cancer cells in the presence of 10b. Interestingly, 10b suppressed the migration of LNCaP cancer cells by up-regulation of epithelial markers (E-cadherin) and down-regulation of mesenchymal markers (vimentin). CONCLUSION: Our findings revealed that the compound 10b may be a new potent candidate with multiple biological activities to design therapeutic agents against different cancers. Synthesis and evaluation of in vitro cytotoxic effects of triazol/spiroindolinequinazolinedione, triazol/indolin-3-thiosemicarbazone and triazol/thiazol-indolin-2-one conjugates.

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology.

An architectural polymer containing hydrophobic isoxazole-based dendron and hydrophilic polyethylene glycol linear tail is prepared by a combination of the robust ZnCl2 catalyzed alkyne-nitrile oxide 1,3-dipolar cycloaddition and esterification chemistry. This water soluble amphiphilic telodendrimer acts as a macromolecular biologically active agent and shows concentration dependent reduction of glioblastoma (U251) cell survival.

Peanut shell as a green biomolecule support for anchoring Cu2O: a biocatalyst for green synthesis of 1,2,3-triazoles under ultrasonic irradiation.

Cu2O supported on peanut shell (Cu2O@PS) was prepared by the reaction of copper acetate and peanut shell powder as a naturally available biopolymer support. The prepared catalyst was used as an efficient and reusable heterogeneous catalyst in the click reaction of benzyl halide or phenacyl bromides, acetylenes and sodium azide for the synthesis of potentially biologically active 1,2,3-triazoles under ultrasonic irradiation in EtOH-H2O as green solvent.

Palladium-catalyzed, unsymmetrical homocoupling of thiophenes via carbon-sulfur bond activation: a new avenue to homocoupling reactions.

The Pd-catalyzed, CN-directed unsymmetrical synthesis of 2,4'-bithiophenes via an unprecedented homocoupling reaction is described. The NH2/CN/SMe arrangement breaks the routine. The cooperative performance of the functional groups in thiophenes would open up a new vision in the field of metal catalysis homocoupling reactions by joining the electrophilic and nucleophilic motifs of the substrate. Furthermore, it is found that the α-chelating effect of the carbonyl group in amino thiophene offers a new class of synthetic protocols for C-N cross-coupling with arylboronic acids. The bidentate N,O-chelation provides a series of advantages such as copper-catalyzed, ligand- and base-free under open-flask conditions. Interestingly, the combination of the C-N cross-coupling/homocoupling reactions in a domino fashion led to the bithiophene adducts featuring the C(Ar)-N bond cleavage in the nitrogen that bridged between the two thiophene units.

Continuous flow room temperature reductive aqueous homo-coupling of aryl halides using supported Pd catalysts.

A convenient and environmentally friendly protocol for the preparation of biaryls at room temperature under continuous flow conditions is reported. A simple reductive homo-coupling Ullmann-type reaction was performed in an H-Cube mini using commercially available supported Pd catalysts under mild reaction conditions, with quantitative conversion to target products. Commercial Pd catalysts were found to be highly stable under the investigated reaction conditions, with a minimum Pd leaching into solution after several reaction runs (ca. 20 h on stream).

Copper ferrite nanoparticles: an efficient and reusable nanocatalyst for a green one-pot, three-component synthesis of spirooxindoles in water.

A green reaction of isatins, active cyanomethanes, and cyclic 1,3-dicarbonyl derivatives for the efficient and simple one-pot three-component synthesis of spirooxindole fused heterocycles in refluxing water by use of magnetically recoverable and reusable catalyst is reported. The features of this procedure are, the use of magnetically recoverable and reusable catalyst, mild reaction conditions, high to excellent product yields, operational simplicity, and easy workup procedures. Most importantly of all, easy magnetic separation of the catalyst eliminates the requirement of catalyst filtration after completion of the reaction. Furthermore, the catalyst remained highly active even after 5 repeated uses.

Highly efficient construction of bisspirooxindoles containing vicinal spirocenters through an organocatalytic modified Feist-Bénary reaction.

We have developed an organocatalytic modified Feist-Bénary reaction of cyclic dicarbonyl compounds, isatins and cyclic α-bromo dicarbonyl compounds. This method affords bisspirooxindole-fused dihydrofurans containing two vicinal spiro centers. To the best of our knowledge, employing cyclic α-halo dicarbonyl compounds for the synthesis of bisspirooxindole-fused dihydrofurans has not been previously reported.

An efficient one-pot organocatalyzed synthesis of spiro[chroman-3,6'- furo[2,3-d]pyrimidine]-tetraones.

An efficient synthesis of new spiro[chroman-3,6'-furo[2,3-d]pyrimidine]- tetraones by an organocatalyzed three-component condensation reaction of aldehydes, barbituric acids and 3-bromo-4-hydroxy-2H-chromen-2-one in refluxing acetic acid in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is reported. We are hopeful that the products will lead to a wider range pharmacological and physiological activity.

A diastereoselective synthesis of pyrano fused coumarins via organocatalytic three-component reaction.

A new method for the synthesis of pyran fused coumarins by 3-bromo-4-hydroxycoumarins as cyclic α-halo ketones based on an organocatalyst assisted three-component tandem reaction is investigated. To the best of our knowledge, cyclic α-halo ketones have not yet been used for the synthesis of pyran fused coumarins.

Organocatalytic three-component cascade reaction for the synthesis of spiro[indeno[1,2-b]furan]-triones.

New methods for the synthesis of spiro compounds containing dihydrofuran and coumarin moieties from 3-bromo-4-hydroxycoumarins as cyclic α-halo compound based on a pyridinium-ylide-assisted three-component tandem reaction is investigated. To the best of our knowledge, employing cyclic α-halo compounds for the synthesis of dihydrofuran-fused coumarin via a pyridinium ylide has not been reported yet.

Dimethyl 2-(1-benzyl-2-oxoindolin-3-yl-idene)-1,3-dithiole-4,5-dicarboxyl-ate.

In the title compound, C(22)H(17)NO(5)S(2), the dithiole and oxindole rings are almost coplanar [dihedral angle = 2.71 (8)°] and the phenyl ring makes a dihedral angle of 73.65 (5)° with the oxindole ring. Inter-molecular π-π contacts between adjacent oxindole and dithiole rings [centroid-centroid distance = 3.7273 (11) Å] stabilize the crystal packing.

Simple three-component method for the synthesis of spiroindeno[1,2-b]pyrido[2,3-d]pyrimidine-5,3'-indolines.

An efficient, simple, and catalyst-free synthesis of spiroindeno[1,2-b]pyrido[2,3-d]pyrimidine-5,3'-indolines and spiroacenaphthylene-1,4'-indeno-1,5'-pyrido[2,3-d]pyrimidines by the three-component reaction of 1,3-indandione, amino uracils and isatins or acenaphthylene-1,2-dione in refluxing ethanol is reported.

Sonochemical multi-component synthesis of spirooxindoles.

New and efficient multi-component methods have been developed for the synthesis of spirooxindoles in the presence of a catalytic amount of p-TSA as an inexpensive and available catalyst in EtOH under ultrasound irradiation. The method is simple, starts from readily accessible commercial starting materials, and provides biologically interesting products in good yields and short reaction times.

Ultrasound-assisted synthesis of 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene-1,3(2H)-dione) derivatives.

A simple and efficient procedure for the synthesis of 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene-1,3(2H)-dione) derivatives, 2,2'-(2-oxo-1,2-dihydroacenaphthylene-1,1-diyl)bis(1H-indene-1,3(2H)-dione) and 2,2'-(1,3-dioxo-2,3-dihydro-1H-indene-2,2-diyl)bis(1H-indene-1,3(2H)-dione) by the reaction of 1,3-indandione and isatins or acenaphthylene-1,2-dione or ninhydrine in ethanol under ultrasonic irradiation in the presence of p-TSA is reported. The advantages of this method are the use of an inexpensive and readily available catalyst, easy work-up, good yields, and the use of ethanol as a solvent that is considered to be relatively environmentally benign.

Efficient and green sonochemical synthesis of 3,3-bis(4-(dimethylamino)phenyl)indolin-2-ones.

A simple, green sonochemical synthesis of 3,3-bis(4-(dimethylamino)phenyl)indolin-2-ones, 2,2-bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-dione, 2,2-bis(4-(dimethylamino)phenyl)acenaphthylen-1(2H)-one and 5-(4-(dimethylamino)phenyl)-5-hydroxypyrimidine-2,4,6(1H,3H,5H)-triones using indium(III) chloride catalyst in aqueous media at room temperature is reported. Good yields, easy workup, short reaction time and the use of water as a solvent that is considered to be relatively environmentally benign are advantages of this new method.

Three-component synthesis of new unsymmetrical oxindoles via Friedel-Crafts type reaction.

The synthesis of 2-(3-(4-(dimethylamino)phenyl)-2-oxoindolin-3-yl)-1H-indene-1,3(2H)-diones as new unsymmetrical oxindoles via a Friedel-Crafts type three-component reaction of 1,3-indandion, N,N-dimethylaniline and isatins in ethanol in the presence of LiClO4 is reported.

Three-component synthesis of 2-oxoindolin-3-ylphosphonates.

A one-pot, three-component and catalyst-free method for the efficient and simple synthesis of dialkyl 3-(dicyanomethyl)-2-oxoindolin-3-ylphosphonates at 50 degrees C under solvent-free conditions is reported. The features of this procedure are mild reaction conditions, high yields of products, and operational simplicity.

Chromeno[2,3-d]pyrimidine-triones synthesis by a three-component coupling reaction.

A simple and one-pot synthesis of new chromeno[2,3-d]pyrimidine-triones by a three-component condensation reaction of barbituric acids, aldehydes and cyclohexane-1,3-diones in refluxing ethanol in the presence of p-toluenesulfonic acid (p-TSA) for 3-10 h is reported. Two cyclohexane-1,3-diones, four barbituric acids and six substituted aldehydes were chosen for the library validation. Prominent among the advantages of this new method are operational simplicity, good yields and easy work-up procedures employed.