Regioselective synthesis, stereochemical structure, spectroscopic characterization and geometry optimization of dispiro[3H-indole-3,2′-pyrrolidine-3′,3″-piperidines] (original) (raw)

A strategic approach to the synthesis of functionalized spirooxindole pyrrolidine derivatives: in vitro antibacterial, antifungal, antimalarial and antitubercular studies

A series of spiro[pyrrolidin-2,3 0-oxindoles] has been synthesized by exo-selective 1,3-dipolar cycloaddition reaction of a stabilized azomethine ylide, generated in situ by thermal [1,5]-prototropy, across various (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-diones. The stereochemistry of these N-heterocycles has been confirmed using an X-ray diffraction study. To rationalize the observed regio-and stereoselectivity, DFT calculations at the B3LYP/6-31G(d,p) level were employed. It was found that this reaction preferentially affords the kinetic product. The compounds have been screened for their in vitro antibacterial, antifungal, antimalarial and antitubercular activities. Several compounds exhibited good activities comparable to those of established standard drugs.

A facile synthesis of novel pyridone-annelated spirooxindolepyrrolidines via 1,3-dipolar cycloaddition

Monatshefte für Chemie - Chemical Monthly, 2015

A series of novel pyridine-annelated spirooxindole-3,2 0 -pyrrolidines was prepared via 1,3-cycloaddition reaction involving N-methylmaleimide as 1,3dipolarophile and the appropriate azomethine ylide. The latter 1,3-dipolar species were generated in situ via decarboxylative condensation reaction of the particular aamino acid with pyridine-annelated isatin in aqueous methanol under reflux. The structures of these new spirooxindole cycloadducts are based on microanalytical, spectral (IR, HRMS, and NMR), and X-ray crystal data. Graphical Abstract R Keywords 1,2,9-Trioxopyrrolo[2,3-f]quinoline Á Azomethine ylide Á 1,3-Cycloaddition Á Spirooxindolepyrrolidines Á X-ray crystal data R. M. Al-As'ad Á M. M. El-Abadelah (&) Á

Synthesis of highly substituted spiropyrrolidines via 1, 3-dipolar cycloaddition reaction of N-metalated azomethine ylides. A new access to spiropyrrolines derivatives

Mediterranean Journal of Chemistry, 2015

1,3-dipolar cycloaddition of (E)-arylidene-(2H)-indanones 1 (Ar = Ph, p-MeC6H4, p-MeOC6H4, p-ClC6H4, p-NO2C6H4) and (E)-2-arylidene-(2H)-tetralones 2 (Ar = Ph, p-MeC6H4, p-MeOC6H4, p-ClC6H4, p-NO2C6H4) to N-metalated azomethine ylides 3 generated from methyl N-arylideneglycinate in the presence of silver acetate produces in good yields novel methyl 1-oxo-2',4'-diaryl-1,3-dihydrospiro[indene-2,3'-pyrrolidine]-5'-carboxylates 4 and methyl 1-oxo-2',4'-diaryl-3,4-dihydro-1H-spiro[naphthalene-2,3'-pyrrolidine]-5'carboxylates 5. The cycloaddition proceeds in regio-and stereoselective manner (100%) at room temperature to afford respectively the syn-endo cycloadducts 4 and 5 via metallo-azomethine ylides. The regio-and stereochemistry of the spiranic adducts have been established on the basis of spectroscopic data and elemental analysis, corroborated by single-crystal X-ray crystallographic analysis of the heterocycles 4ci, 4bg and 5bi. The endo-pyrrolidines 4 were brominated by N-bromosuccinimide to give finally the dehydrobrominated 3, 4dihydro-2H-pyrrole derivatives 6. The spiro-adducts 4 and their corresponding oxidation products 6 are fluorescent in solution.

Regiospecific Synthesis and Rationalization of the Regiodivergence Some Spirooxindoles as Expected Antioxidant Agents

Al-Azhar Bulletin of Science, 2016

The spirooxindolo pyrrolidine frameworks form core units of many naturally occurring molecules possess significant pharmacological activities. The [3+2] cycloaddition reactions of azomethine ylides has been realized through multi-component reaction (MCR) affording regiospecific spiroindoline-3, 2'-pyrrolidine derivatives. The reactivity of the spiroindoline (increase E HOMO value) has been depended upon electron repelling and attracting groups. The behavior of spiroindoline towards carbon electrophile and nitrogen nucleophile can be investigated. All compound structures are fully supported by spectroscopic data and elemental analysis.The antioxidant activity for these synthesized compounds could be expected that highly antioxidant activity was with compounds which proved to possess high HOMO values

Novel Spiro-pyrrolizidine-Oxindole and Spiropyrrolidine-Oxindoles: Green synthesis under Classical, Ultrasonic, and microwave conditions and Molecular docking simulation for antitumor and type 2 diabetes

2022

Novel spiropyrrolizine / pyrrolidineoxindole moieties were synthesized chemo-, and regio-selectively in high yields from knoevenagel reaction of bis[arylmethylidene]piperidin-4-ones, isatin and L-proline or sarcosine under classical, ultrasonic, and microwave conditions. Seven derivatives of the synthesized dispiro-pyrrolizidine-oxindole and spiropyrrolidine were screened for their antitumor activity against two cell lines MCF-7 (breast cancer) and HEPG2 (liver cancer). The results of biological activity indicated that the tested derivatives showed potent activity against breast cancer cell MCF-7. Molecular docking simulation screening studies of the synthesized products with each of the receptors of (3hb5) for breast cancer and (4k9g) for liver cancer and their interaction with 1H5U of glycogen phosphorylase B, type 2 diabetes drug were examined. The docking study of dispiro-pyrrolizidine-oxindole and spiropyrrolidine showed promising results with several derivatives.

Antimicrobial Activity and In Silico Molecular Docking Studies of Pentacyclic Spiro[oxindole-2,3′-pyrrolidines] Tethered with Succinimide Scaffolds

Applied Sciences

Three-component cascade reactions of (E)-3-arylidene-1-methyl-pyrrolidine-2,5-diones, L-valine and various isatin derivatives are described. A series of 17 spiropyrrolidine derivatives with wide structural complexity and diversity have been thus obtained in moderate to excellent yields under mild reaction conditions. The structure and stereochemistry of these N-heterocyclic cycloadducts has been established by spectroscopic techniques and unambiguously confirmed by a single-crystal X-ray diffraction analysis performed on one derivative. UV-visible spectra have been recorded for all new compounds. Furthermore, the synthesized N-heterocyclic compounds have been screened for their in vitro antibacterial and antifungal activities. Several derivatives exhibited moderate to good activities, comparable to those of the known standard drugs Amphotericin B and Tetracycline. Structural activity relationships (SARs) and molecular docking of the most promising derivatives into the binding sites ...