Spirooxindole Derivatives Research Articles

Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole-pyrrolidine derivatives and their biological applications.

A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including [Formula: see text], [Formula: see text], 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a-r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f [Formula: see text] showed significant cytotoxic activity compared to the standard drug doxorubicin [Formula: see text].

A green one-pot three-component synthesis of spirooxindoles under conventional heating conditions or microwave irradiation by using Fe3O4@SiO2-imid-PMAn magnetic porous nanospheres as a recyclable catalyst

An efficient, green and environmentally procedure for the synthesis of spirooxindole derivatives has been developed by a one-pot three-component reaction of isatin derivatives, activated methylene, and 1,3-dicarbonyl compounds in the presence of Fe3O4@SiO2-imid-PMAn magnetic nanocatalyst under conventional heating conditions in water or microwave irradiation under solvent-free conditions. The reactions under conventional heating conditions were compared with the microwave-assisted reactions. The suggested method offers several advantages such as excellent yields, short reaction times, operational simplicity, a cleaner reaction, absence of any tedious workup or purification and ease of recovery and reusability of the catalyst by a magnetic field. In addition, the excellent catalytic performance in a water medium and the easy preparation, thermal stability and separation of the catalyst make it a good heterogeneous system and a useful alternative to other heterogeneous catalysts. The catalyst can be easily recovered by a magnetic field and reused for six consecutive reaction cycles without significant loss of activity. Also, the morphology of Fe3O4@SiO2-imid-PMAn, particle size distribution and leaching of nano H3PMo12O40 (PMAn) after reaction cycles were investigated by scanning electron microscopy (SEM), dynamic light scattering (DLS), and inductively coupled plasma (ICP) analyzer.

ChemInform Abstract: [bmim]OH: An Efficient Catalyst for the Synthesis of Mono and Bis Spirooxindole Derivatives in Ethanol at Room Temperature

Abstractvia three‐component reactions of isatin, malononitrile and carbonyl compounds (III) or (V) possessing a reactive α‐methylene group

ChemInform Abstract: Construction of Highly Enantioselective Spiro‐Oxindole Derivatives with Fused Chromene via Organocascade Catalysis.

A first highly enantioselective addition of naphthols and sesamol to indolylidene cyanoacetate derived from isatins was carried out in the presence of bi-functional quinine thiourea as organocatalyst. Under optimized reaction conditions the present catalytic system gave spiro-oxindole derivatives with excellent yield and enantioselectivity (up to 99%) at very low catalyst loading (2 mol%). The absolute configuration of 3i was determined by single X-ray crystallographic analysis to be the S isomer of the product. A catalytic cycle is proposed based on NMR, IR and kinetic studies.

Design, Synthesis, and Biological Activities of Spirooxindoles Containing Acylhydrazone Fragment Derivatives Based on the Biosynthesis of Alkaloids Derived from Tryptophan.

On the basis of the biosynthesis of alkaloids derived from tryptophan and considering the wide use of spirooxindole in drug molecular design, a series of novel spirooxindole derivatives containing an acylhydrazone moiety were designed, synthesized, and first evaluated for their biological activities. The results of bioassays indicated that the target compounds possessed good activities against tobacco mosaic virus (TMV); especially compound 4, containing a tert-butyl at the benzene ring, exhibited the best antiviral activity in vitro and inactivation, curative, and protection activities in vivo (48.4%, 58 ± 0.4, 55.2 ± 2.3, and 49.7 ± 1.1% at 500 μg/mL, respectively) compared with ribavirin (38.2, 36.4 ± 0.2, 37.5 ± 0.2, and 36.4 ± 0.1% at 500 μg/mL, respectively) and harmine (44.6, 40.5 ± 0.2, 38.6 ± 0.8, and 42.4 ± 0.6% at 500 μg/mL, respectively). At the same time, these compounds exhibited fungicidal activity selectively against certain fungi; most of these derivatives exhibited >60% fungicidal activity against Physalospora piricola at 50 mg/kg. Additionally, compounds 25 and 14 displayed excellent insecticidal activities (60% motality against C.pipiens pallens at 0.25 mg/kg) even at very low concentrations.

Electrocatalytic Multicomponent Reaction for Synthesis of Nanoparticles of Spirooxindole Derivatives from Isatins, Malononitrile, and Dimedone

An electrocatalytic multicomponent synthesis of nanoparticles of spirooxindole is described, using an electrogenerated base of the anion of propanol in a one‐pot, three component condensations of an isatins, dimedone, and malononitrile in an undivided cell in the presence of sodium bromide as an electrolyte at 50°C.

ChemInform Abstract: Synthesis of Novel Spirooxindole Derivatives Using N‐Phenylpiperazine as an Organocatalyst.

ChemInform Abstract: Synthesis of Novel Spirooxindole Derivatives Using N‐Phenylpiperazine as an Organocatalyst.

Brønsted or Lewis Acid Initiated Multicomponent Cascade Reaction: Diastereoselective Synthesis of Imidazolidinyl Spirooxindole Derivatives

AbstractOne peculiar type of aza‐hetero‐imidazolidinyl spirooxindole derivatives was efficiently constructed by the three‐component [2+2+1] cascade reaction of 1,4‐oxazepines with diazo‐oxindoles. Iron(II) trifluoromethanesulfonate [Fe(OTf)2] or p‐toluenesulfonic acid monohydrate (p‐TsOH⋅H2O) proved to be optimal catalysts for this transformation, providing the desired products in high yields (up to 94 %) with excellent diastereoselectivity (up to 99:1 dr). Experimental studies showed that the reaction rate of Brønsted acid catalysis was faster than that of Lewis acids. Furthermore, the mechanism was theoretically investigated for Brønsted acid as the catalyst and a reaction pathway was proposed. DFT calculations suggested that the diazo‐oxindole can act as a 1,3‐dipole to add to a C=N double bond of 1,4‐oxazepine, which forms a 4,5‐dihydro‐1H‐1,2,3‐triazole intermediate. Subsequently, the releasing of N2 is the rate‐limiting step of the whole catalytic cycle.

Gold catalyzed double condensation reaction: Synthesis, antimicrobial and cytotoxicity of spirooxindole derivatives

Microwave assisted synthesis of spirooxindoles via tandem double condensation between isatins and 4-hydroxycoumarin under gold catalysis is reported. The reaction is practical to perform, since the products can be isolated by simple filtration without requiring tedious column chromatography. The scope of this chemistry is exemplified by preparing structurally diverse spirooxindoles (22 examples) in excellent yields. Antimicrobial evaluation of the synthesized compounds revealed that three compounds (3a, 3f and 3s) exhibited significant MIC values in comparison to the standard drugs. Molecular docking studies of these compounds with AmpC-β-lactamase receptor revealed that 3a exhibited minimum binding energy (−117.819kcal/mol) indicating its strong affinity towards amino acid residues via strong hydrogen bond interaction. All compounds were also evaluated for their in vitro cytotoxicity against COLO320 cancer cells. Biological assay and molecular docking studies demonstrated that 3g is the most active compound in terms of its low IC50 value (50.0μM) and least free energy of binding (−8.99kcal/mol) towards CHK1 receptor, respectively.

ChemInform Abstract: An Efficient Synthesis of 1‐(4H‐1,2,4‐Triazol‐3‐yl)‐hexahydroquinoline‐3‐carbonitrile and Their Spiro Derivatives from β‐Enaminones.

AbstractCyclic enamines bearing a triazole ring undergo simple and facile Michael addition reactions with various arylidenemalononitriles or oxindoles affording the title hydroquinoline carbonitriles or spirooxindole derivatives, respectively.

ChemInform Abstract: Construction of Spirocyclic Oxindoles Through Regio‐ and Stereoselective [3 + 2] or [3 + 2]/[4 + 2] Cascade Reaction of α,β‐Unsaturated Imines with 3‐Isothiocyanato Oxindole.

On the basis of asymmetric regioselective [3+2] or [3+2]/[4+2] cascade reaction of 3-isothiocyanato oxindoles with C=C and C=N bonds of α,β-unsaturated methanesulfonamides, diversified S-containing heterocyclic spirooxindole derivatives could be obtained in high yields along with good to excellent diastereo- and enantioselectivities under mild conditions in the presence of cinchona alkaloid-derived organocatalysts.

ChemInform Abstract: Synthesis of Heterocyclic Scaffolds Through 6‐Aminouracil‐Involved Multicomponent Reactions

AbstractReview: 98 refs.

ChemInform Abstract: A Convenient and Rapid Microwave‐Assisted Synthesis of Spirooxindoles in Aqueous Medium and Their Antimicrobial Activities.

AbstractFunctionalized spirooxindole derivatives are simply and eco‐friendly synthesized by an one‐pot, three‐component aqueous phase protocol under microwave irradiation with good diastereoselectivity.

Cerium oxide-catalyzed multicomponent condensation approach to spirooxindoles in water

An efficient and facile green synthesis of spirooxindole derivatives bearing pyrano[2,3-c]pyrazole moiety has been achieved viaa[Formula: see text]-NPs catalyzed four-component reaction in water. The protocol offers an environmentally benign and effective approach to highly functionalized and biologically interesting spiro[indoline-3,4[Formula: see text]-pyrano[2,3-c]pyrazole] derivatives. The synthesized compounds exhibit potent antioxidant and antibacterial activities.

ChemInform Abstract: Stereoselective Synthesis of Spirooxindole Derivatives Using an Organocatalyzed Tandem Michael—Michael Reaction.

A highly efficient stereoselective method for the synthesis of functionalized spirooxindole derivatives with three stereogenic centers was realized through an organocatalytic tandem Michael-Michael reaction. By employing (S)-α,α-diphenylprolinol trimethylsilyl ether as the catalyst and N,N'-bis[3,5-bis(trifluoromethyl)phenyl]thiourea as the cocatalyst, the reaction between N-tritylisatylidenemalononitriles and (E)-7-alkyl-7-oxohept-5-enals yields the desired spirooxindole products in good yields (76-95%) and with excellent diastereoselectivities (up to 97 : 3 dr) and enantioselectivities (up to 98% ee), which can be stereoselectively converted into the spiro[indoline-3,8'-isoquinoline] derivative through an intramolecular reductive amination reaction.

Convenient One-Pot Synthesis of Spirooxindole Derivatives Containing a 1,3,4-Thiadiazine Scaffold

A useful strategy for the construction of spirocyclic oxindoles bearing a 1,3,4-thiadiazine skeleton is reported. The desired products were obtained in high yields under mild conditions.

Synthesis of Novel Spirooxindole Derivatives Using N-Phenylpiperazine as an Organocatalyst

Synthesis of Novel Spirooxindole Derivatives Using N-Phenylpiperazine as an Organocatalyst

ChemInform Abstract: Synthesis of New Spirooxindole Derivatives Through 1,3‐Dipolar Cycloaddition of Azomethine Ylides and Their Antitubercular Activity.

AbstractNon‐stabilized azomethine ylides, generated in situ from isatin (II) or quinone (VI) and L‐proline (III), are reacted with bis(arylidene)indan‐2‐ones (I) as dipolarophiles in a 1,3‐dipolar cycloaddition.

Construction of Spirocyclic Oxindoles through Regio- and Stereoselective [3+2] or [3+2]/[4+2] Cascade Reaction of α,β-Unsaturated Imines with 3-Isothiocyanato Oxindole.

On the basis of asymmetric regioselective [3+2] or [3+2]/[4+2] cascade reaction of 3-isothiocyanato oxindoles with C=C and C=N bonds of α,β-unsaturated methanesulfonamides, diversified S-containing heterocyclic spirooxindole derivatives could be obtained in high yields along with good to excellent diastereo- and enantioselectivities under mild conditions in the presence of cinchona alkaloid-derived organocatalysts.

ChemInform Abstract: A Cesium Fluoride Promoted Efficient and Rapid Multicomponent Synthesis of Functionalized 2‐Amino‐3‐cyano‐4H‐pyran and Spirooxindole Derivatives.

Abstract A rapid, one-pot and highly efficient protocol for the synthesis of pharmaceutically interesting functionalized 2-amino-3-cyano-4 H -pyran and spirooxindole derivatives has been developed using commercially available CsF as a catalyst in the reaction of malononitrile and aryl aldehydes or isatins with 1,3-cyclohexanediones. The major advantages of this methodology are excellent yield at ambient temperature, very short reaction time (5–10 min), and use of an inexpensive catalyst.