Reactions of Hydroxyazolidines with π-Donor Heterocycles. 3. Reaction of 1-Acetyl-5-hydroxypyrazolidines with Oxindoles

The reaction of oxindoles with 5-hydroxypyrazolidines on the surface of potassium fluoride-modified alumina leads to 3-(5-pyrazolidinyl)oxindoles. The structure of these products was studied.     

新型螺环六氢山酮素-氧化吲哚-苯并呋喃酮类拼接物的合成及其抗白血病细胞增殖活性

以色酮-氧化吲哚合成子与3-烯基苯并呋喃酮为原料,在催化剂1,8-二氮杂二环十一碳-7-烯作用下,在二氯甲烷中发生Michael/Michael加成关环反应,合成了6个未见文献报道的螺环六氢山酮素-氧化吲哚-苯并呋喃酮类拼接物(3a^3f),产率75%~87%,dr值3/1~5/1,其结构经1H NMR,13C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了3a^3f对人白血病细胞(K562)的体外抗增殖活性。结果表明:化合物3c,3e和3f对K562增殖有一定的抑制活性。     

Synthesis,characterization and application of alumina/ vanadium pentoxide nanocomposit by sol–gel method

In this work, we report the preparation of Al₂O₃/V₂O₅ nanocomposit using vanadium and aluminum nitrate by sol–gel method. Characterization of nanocomposit was carried out by powder X‐ray diffractometry (XRD), Fourier transform infrared (FT‐IR), scanning electron microscopy (SEM), Energy‐Dispersive X‐ray (EDX) and UV spectroscopy. Then, applicability of the synthesized nanocomposit was tested as a nanocatalyst for the synthesis of diindolyl oxindole derivatives, an important class of potentially bioactive compounds. The products were obtained in good to high yields from one‐pot three‐component condensation of isatin with indole. Also, this nanocatalyst has been reused several times, without observable loss of activity.     

Copper-Catalyzed Cyanopropylation of Activated Alkenes

A practical copper-catalyzed alkylarylation of activated alkenes with azobisisobutyronitrile (AIBN) and beyond has been developed, in which incorporation of 3^o nitrile moiety into an oxindole scaffold proceeded smoothly through cascade radical addition/C(sp²)-H cyclization. The use of readily available AIBN as radical source and inexpensive CuI as catalyst, as well as broad substrate scope and the simplicity of operation and handling, make this protocol a highly attractive approach to oxindoles bearing 3^o nitrile moiety.     

Reduction of 3‐Acyl Derivatives of Oxindoles,Benzo[b]furan‐2‐ones,and Benzo[b]thiophen‐2‐ones to the Corresponding Alkyl Derivatives by Sodium Borohydride–Acetic Acid

It was found that 3‐acyl derivatives of oxindoles, benzo[b]furan‐2‐ones, and benzo[b]thiophen‐2‐ones could be efficiently and conveniently reduced to the corresponding alkyl derivatives by pelletized sodium borohydride in acetic acid. A typical procedure involves heating the acylated substrates for approximately 90 min in a slurry of glacial acetic acid and sodium borohydride to provide the 3‐alkyl product in yields ranging from 62% to 96%. This synthetic methodology represents a convenient approach to the synthesis of the alkyl derivatives.     

Synthesis and computational studies of potent antimicrobial and anticancer indolone scaffolds with spiro cyclopropyl moiety as a novel design element

The indolones nucleus is the central core to develop new effective anticancer agents and its substitution at the 3-position can affect antitumor activity, 3-spirocyclopropyl-2-oxindoles have attracted the scientist's community to design and develop expedition's strategies towards their construction and explore the potential of this useful scaffold with their newer derivatives in medicinal world. The present paper describes the synthesis of 3-spirocyclopropyl-2-indolone derivatives in three steps via synthesis of ylide leading to methylene-indolinones followed by the formation of the final product spirocyclopropyl oxindole derivatives with improved yields. In this milieu we considered motivating to advance exploration the biological potencies and computational studies of our newly synthesized molecules. The aimed target molecules were screened for antimicrobial and anticancer activities where they exhibited substantial effective antimicrobial activities. Amongst them, potent compound, bromospirocyclopropyl indolone, 6d displayed encouraging MIC ranging from 0.007 to 0.49 μg/mL for gram positive microbes and also substantial anticancer activity with an IC₅₀ of 11.5 μg/mL. Finally, the computational modelling studies were performed to explore structure-activity relationship analysis. Active site of receptor protein shows docking scores of these molecules as - 5.78 kcal/mol and ?5.097 kcal/mol for the docked target proteins. The binding energy of the best score is found to be ?41.67 kcal/mol to ?44.67 kcal/mol. Thus, the present paper efficaciously validated spirocyclopropyl indolone framework for drug candidates as potent anticancer as well as antimicrobial compounds.     

Remote regioselective organocatalytic asymmetric [3+2] cycloaddition of N-2,2,2-trifluoroethyl isatin ketimines with cyclic 2,4-dienones

An organocatalytic asymmetric [3+2] cycloaddition of trifluoromethyl-containing azomethine ylides with cyclic 2,4-dienones was developed.The process enables efficient incorporation of CF3 groups into functionalized spiro [pyrro lid in-3,2'-oxindoles] in high yields with good to excellent enantio-and diastereoselectivities.     

Rapid determination of oxindole alkaloids in cat's claw by HPLC using ionic liquid‐based microwave‐assisted extraction and silica monolithic column

Cat's claw is a large woody vine with hook‐like thorns, and has been traditionally used to treat inflammatory disorders in South and Central America. In this study, a rapid, validated high‐performance liquid chromatographic (HPLC) method using a silica monolithic column was developed for the simultaneous determination of oxindole alkaloids, namely rhynchophylline, pteropodine, isomitraphylline and isopteropodine, in cat's claw. The ionic liquid‐based microwave‐assisted extraction (ILMAE), considered as an environmentally friendly and powerful tool, was first applied in the extraction of oxindole alkaloids. To optimize the HPLC method, the stationary phases, pH values of mobile phase and flow rates were investigated. The validated HPLC method using a Monolithic RP_18e column (100 × 4.6 mm) enables these analytes to be separated almost twice as fast as with a conventional particulate column (~16 vs ~30 min) with limits of quantification and detection of 0.5 and 0.15 μg/mL, respectively. The ILMAE conditions were optimized by the Taguchi orthogonal array design. In comparison with conventional water boiling extraction, ILMAE offers almost four times higher yields within an extremely short extraction time. The developed HPLC coupled with ILMAE method could be efficient and practical for rapid determination of oxindole alkaloids in cat's claw.     

A spirocyclic oxindole analogue:Synthesis and antitumor activities

A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3’-pyrrolo[2,3-b]pyridin]-2’（1’H）-one 1 is described.The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ring by an intramolecular Buchwald-Hartwig amidation of carboxylic ami Je and aryl chloride.A small library was obtained by reductive amination of 1 with various aldehydes and was screened against human lung cancer cell A549,human liver cancer cell BEL7402,and human colon cancer cell HCT-8.The results show that most of the 1（?）rary compounds 2 have some inhibitory activities.2-（Trifluoromethoxy） benzylic substituted spirocyclic azaoxindole 2e was identified as a nanomolar inhibitor against human lung cancer cell A-549(IC₅₀=50 nmol/L).     

Efficient 1,6-addition reactions of 3-substituted oxindoles: Access to isoxazole-fused 3,3′-disubstituted oxindole scaffolds and hexahydro-1h-pyrido[2,3-b]indol-2-one scaffolds

Developed herein is a new methodology for a hybrid of two pharmacophoric oxindole and isoxazole motifs to construct isoxazole-fused 3,3′-disubstituted oxindole scaffolds via an efficient 1,6-addition reaction of 3-substituted oxindoles to 3-methyl-4-nitro-5-alkenylisoxazoles, which might generate novel drug-like molecules for biological screenings. The method gives an easy access to a series of isoxazole-fused 3,3′-disubstituted oxindoles with 26 examples in high yields (up to 92% yield) and good diastereoselectivity (up to >20:1), which makes possible the synthesis of libraries under similar circumstances. Subsequently, a sequential Michael addition/amidation/reductive cyclization process was designed for accessing this hexahydro-1H-pyrido[2,3-b]indol-2-one scaffold, which is a key structural skeleton found in a large number of biologically active natural products and pharmaceutical compounds. Hexahydro-1H-pyrido[2,3-b]indol-2-one scaffold 7cg could be obtained in 42.5% overall yield after 4 steps.