Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3771 - 3771

Опубликована: Фев. 13, 2023

N-fused pyrrolidinyl spirooxindole belongs to a class of privileged heterocyclic scaffolds and is prevalent in natural alkaloids synthetic pharmaceutical molecules. To realize the switchable synthesis divergent spirooxindoles for further biological activity evaluation via substrate-controlled strategy, chemically sustainable, catalysis-free, dipolarophile-controlled three-component 1,3-dipolar cycloaddition isatin-derived azomethine ylides with diverse dipolarophiles described this work. A total 40 functionalized were synthesized 76–95% yields excellent diastereoselectivities (up >99:1 dr). The these products can be well-controlled by employing different 1,4-enedione derivatives as EtOH at room temperature. This study provides an efficient strategy afford spectrum natural-like potentially bioactive spirooxindoles.

Язык: Английский

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Spiro-Heterocycles: Recent Advances in Biological Applications and Synthetic Strategies

Tetrahedron, Год журнала: 2025, Номер unknown, С. 134468 - 134468

Опубликована: Янв. 1, 2025

Язык: Английский

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Study of Cytotoxicity of 3-Azabicyclo[3.1.0]hexanes and Cyclopropa[a]pyrrolizidines Spiro-Fused to Acenaphthylene-1(2H)-one and Aceanthrylene-1(2H)-one Fragments Against Tumor Cell Lines

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3474 - 3474

Опубликована: Апрель 8, 2025

A series of 3-azabicyclo[3.1.0]hexanes and cyclopropa[a]pyrrolizidines spiro-fused to acenaphthylene-1(2H)-one aceanthrylene-1(2H)-one frameworks have been studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), melanoma (Sk-mel-2), osteosarcoma (U2OS), as well murine (B16) cell lines. Using confocal microscopy, it was found that cultivation with the tested compounds led disappearance stress fibers (granular actin distributed diffusely cytoplasm up 56% treated cells) decrease filopodia-like deformations (up 69% after cultivation), which indirectly suggests a motility. The line scratch test showed these cells lose ability move do not fill scratched strip. This also supported by docking simulations actin-related targets (PDB ID: 8DNH, 2Q1N). flow cytometry, impact on mitochondrial membrane potential significant increase number decreased from 10% control 55-80% cyclopropa[a]pyrrolizidine adducts. obtained results support antitumor effect spiro-compounds encourage extension study order improve anticancer reduce toxicological risks.

Язык: Английский

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[3 + 2] Cycloaddition of quinazoline-derived azomethine imines with electron-deficient alkenes to access functionalized fused tricyclic tetrahydropyrazolo[1,5-c]quinazoline frameworks

Tetrahedron, Год журнала: 2025, Номер unknown, С. 134749 - 134749

Опубликована: Май 1, 2025

Язык: Английский

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Gold‐Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor‐Active Spirocyclic Oxindoles from Alkynes and Isatin‐Derived Ketimines

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(34)

Опубликована: Май 19, 2023

Abstract Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole an important core scaffold. We herein describe efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold‐catalyzed cycloaddition reaction terminal alkynes or ynamides with isatin‐derived ketimines. This protocol has good functional group compatibility, uses readily available starting materials, mild conditions, low catalyst loadings no additives. It enables transformation various alkyne groups into cyclic carbamates. Gram‐scale synthesis was achieved DFT calculations verify feasibility mechanistic proposal. Some target products exhibit antiproliferative activity on human tumor cell lines. In addition, one most active compounds displayed remarkable selectivity towards cells over normal ones.

Язык: Английский

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Organocatalytic Diastereoselective Synthesis of Spiro[3-azabicyclo[3.1.0]hexanes] via 1,3-Dipolar Cycloaddition of Azomethine Ylides with Cyclopropenes

Russian Journal of General Chemistry, Год журнала: 2024, Номер 94(4), С. 804 - 823

Опубликована: Апрель 1, 2024

Язык: Английский

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Heteroatom-Controlled Three-Component [4 + 3] or [3 + 2] Annulation of Isatin-Derived Azomethine Ylide with Azadiene: Selective Synthesis of Spirooxindole-diazepines and Density Functional Theory Studies

Organic Letters, Год журнала: 2024, Номер 26(41), С. 8945 - 8950

Опубликована: Окт. 9, 2024

A novel three-component [4 + 3] annulation reaction of isatin-derived azomethine ylides with azadienes was developed for the first time to efficiently synthesize spirooxindole-diazepines incorporating a benzothiophene moiety under catalyst-free conditions. Effects heteroatom azadiene on chemoselectivity investigated. With use bearing benzofuran as substrate, dominant pathway changed an α-[3 2] annulation. When indenone used, distinct γ-[3 observed. Density functional theory calculations revealed that delicate balance between kinetic accessibility and thermodynamic driving force controlled competition different reactions.

Язык: Английский

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11H-Benzo[4,5]imidazo[1,2-a]indol-11-one as a New Precursor of Azomethine Ylides: 1,3-Dipolar Cycloaddition Reactions with Cyclopropenes and Maleimides

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(21), С. 13202 - 13202

Опубликована: Окт. 30, 2022

The possibility of generating azomethine ylides from 11H-benzo[4,5]imidazo[1,2-a]indol-11-one and amino acids is shown for the first time. Based on cycloaddition reactions these with cyclopropenes maleimides, cyclopropa[a]pyrrolizines, 3-azabicyclo[3.1.0]hexanes, pyrrolo[3,4-a]pyrrolizines spiro-fused a benzo[4,5]imidazo[1,2-a]indole fragment were synthesized. Spirocyclic compounds obtained in moderate to good yields, albeit poor diastereoselectivity. Density functional theory calculations performed obtain an insight into mechanism 1,3-dipolar 11H-benzo[4,5]imidazo[1,2-a]indol-11-one-derived cyclopropenes. cytotoxic activity some cycloadducts against human erythroleukemia (K562) cell line was evaluated vitro by MTS-assay.

Язык: Английский

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Direct synthesis of N-functionalized indoles through isomerization of azomethine ylides

Organic & Biomolecular Chemistry, Год журнала: 2024, Номер 22(4), С. 741 - 744

Опубликована: Янв. 1, 2024

A general additive-free strategy based on the isomerization of azomethine ylides generated in situ from isatin and indoline-2-carboxylic acid has been disclosed, providing direct access to N -functionalized indole scaffolds.

Язык: Английский

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Asymmetric Synthesis of Spirooxindole Lactones by Ammonium-tethered Chiral Organocatalysts catalyzed Michael Addition/Cyclization of 3- hydroxyoxindoles with α,β-unsaturated Aldehydes

Current Catalysis, Год журнала: 2023, Номер 12(1), С. 34 - 42

Опубликована: Апрель 1, 2023

Abstract: The ammonium-tethered pyrrolidine-based organocatalyst catalyzed asymmetric Michael addition/cyclization reaction of α,β-unsaturated aldehydes with 3-hydroxyoxindole in aqueous media was developed, giving the spirooxidole lactones high yields enantioselectivities. Background: 3-hydroxyoxindoles α,β- unsaturated is an important method for synthesis chiral spirooxindole derivatives, which are found a wide range biologically active natural products and pharmaceutical agents. Objective: Organocatalyzed reactions one most powerful effective approaches construction complex molecules from relatively simple starting materials. However, major problem associated these organocatalytic system that catalyst loading organic solvents required. In present work, our objective to develop water-compatible aimed at lowering being system. Methods: typical experiment, To solution 2a (0.008 mmol) PhCO2H (0.096 0.5 mL mixture solvent iPrOH/H2O (1:3) added aldehyde (0.4 (0.8 mmol). proceeded room temperature 16 hours, then extracted 10 dichloromethane give cyclized hemiacetal, subjected direct oxidation pyridinium chlorochromate (PCC, 1.2 hours desired lactones. Results: successfully gave excellent (81-95%) moderate enantioselectivities (up 99% ee). diastereoselectivities were poor ranging 1:1.1 1:2.3. Conclusion: using has been developed. performed low (2 mol%) provided (ee: up 99%).

Язык: Английский

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