[Bmim]Br Accelerated One-Pot Three-Component Cascade Protocol for the Construction of Spirooxindole–Pyrrolidine Heterocyclic Hybrids

Abstract

Our synthetic approach for the assembly of structurally complex spirooxindole heterocyclic hybrids was based on an ionic liquid, [bmim]Br mediated one-pot three-component cascade reaction strategy involving 1,3-dipolar cycloaddition reaction of N-1-(2-pyridinylmethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones and azomethine ylide generated in situ from isatin and L-phenyl alanine, affording a series of spirooxindole–pyrrolidine heterocyclic hybrids in good-to-excellent yields. In addition to serving as the reaction medium, [bmim]Br also functioned as a catalyst in this cycloaddition reaction and hence accelerated the reaction rate affording the cycloadducts in short reaction time.

In Vitro Molecular Biology Studies of Spirooxindole Heterocyclic Hybrids

“…This activity seems to increase with that of concentration and incubation period, and the highly active compound was found to be 1b, with the lowest IC50 value of ~24 μg/mL over a treatment time of 48 h. Further testing of the intracellular pathways followed by compound 1b treatment proved that the cancer cells are experiencing the apoptotic mechanism, with the release of oxidative stress mediated by ROS and the involvement of caspases. Comparing the present study results with that of our recently published work [31], it primarily indicates that the spirooxindole- In the present study, the anticancer activity of spirooxindole-pyrrolidine heterocyclic hybrids has been investigated against cancer cells, where the results have proven that all the derivatives exhibit some level of activity. This activity seems to increase with that of concentration and incubation period, and the highly active compound was found to be 1b, with the lowest IC 50 value of~24 µg/mL over a treatment time of 48 h. Further testing of the intracellular pathways followed by compound 1b treatment proved that the cancer cells are experiencing the apoptotic mechanism, with the release of oxidative stress mediated by ROS and the involvement of caspases.…”

“…This activity seems to increase with that of concentration and incubation period, and the highly active compound was found to be 1b, with the lowest IC 50 value of~24 µg/mL over a treatment time of 48 h. Further testing of the intracellular pathways followed by compound 1b treatment proved that the cancer cells are experiencing the apoptotic mechanism, with the release of oxidative stress mediated by ROS and the involvement of caspases. Comparing the present study results with that of our recently published work [31], it primarily indicates that the spirooxindole-pyrrolidine heterocycles are a little less active than the N-pyridinylmethyl-engrafted bisarylmethylidenepyridinones. The lower activity is reflected in the form of IC 50 values, i.e., we observed lower activity at about 12 µg/mL (24 h) for the N-pyridinylmethyl-engrafted bisarylmethylidenepyridinones and at 24 µg/mL (48 h) for the spirooxindole-pyrrolidine heterocycles.…”

“…The required N-pyridyl-spirooxindole-pyrrolidine heterocyclic hybrids 1(a-h) were synthesized in accordance with our recent study [31]. The molecular structure of these heterocyclic hybrids 1(a-h) is shown in Scheme 1.…”

Synthesis, computational docking and molecular dynamics studies of a new class of spiroquinoxalinopyrrolidine embedded chromanone hybrids as potent anti-cholinesterase agents

“…In this context, herein, we explored the potential structurally intriguing new class of heterocycles comprising spiropyrrolidine, quinoxaline and chromanone synthesized in ionic liquid accelerated cycloaddition reaction protocol. Ionic liquids are known as eco-friendly solvents in many organic syntheses [29][30][31] because of their unique properties, including low vapour pressure, high thermal and chemical stability, non-inammability solvating capability, and recyclability, and they play twin roles as reactant and catalyst in organic synthesis. For this reason, their use in organic synthesis has emerged as an important facet of green chemistry.…”

Stereoselective synthesis of dispiroindano pyrrolidines by the [3 + 2] cycloaddition of thiazolo[3,2‐a]indole tethered dipolarophile with azomethine ylides

“…Of late there have been several attempts to employ green chemistry principles to azomethine ylide‐based [3 + 2] cycloadditions; already possessing the inherent advantage of a high degree of atom economy. Among these attempts, the use of ionic liquids [10], task‐specific ionic liquids (TSIL) [11] and deep eutectic solvents (DES) [12] as the reaction media are particularly noteworthy. Very recently, we had reported the stereoselective synthesis of dispiro heterocycles in DES by the [3 + 2] cycloaddition of isatin‐derived azomethine ylides with a thiazolo[3,2‐ a ]indole derivative 3 (Scheme 1) [13].…”