Highly Efficient Synthesis of Spiro[1-azabicyclo[3.2.0]heptane] Frameworks via [3+2]-Cycloaddition

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

An efficient one-pot three-component [3 + 2]-cycloaddition reaction of azomethine ylides, generated in situ from isatins and azetidine-2-carboxylic acid, with different maleimides itaconimides has been investigated. These reactions afford the corresponding spiro dispiro[1-azabicyclo[3.2.0]heptanes] moderate to high yields (up 93%) excellent diastereoselectivities regioselectivities under mild conditions. The method provides a simple route stereoselective synthesis new polyheterocyclic systems such as 3-spiro[1-azabicyclo[3.2.0]heptane]oxindoles spiro-conjugated or fused succinimide moiety. observed diastereo- regioselectivity cycloaddition is reasoned by DFT studies. antiproliferative effect synthesized compounds against cancer cell lines was assessed.

Язык: Английский

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Organic Chemistry in Russian Universities. Achievements of Recent Years

Russian Journal of Organic Chemistry, Год журнала: 2024, Номер 60(8), С. 1361 - 1584

Опубликована: Авг. 1, 2024

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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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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Study of Cytotoxicity of Spiro-Fused [3-Azabicyclo[3.1.0]hexane]oxindoles and Cyclopropa[a]pyrrolizidine-oxindoles Against Tumor Cell Lines

Pharmaceuticals, Год журнала: 2024, Номер 17(12), С. 1582 - 1582

Опубликована: Ноя. 25, 2024

Background: A series of spiro-fused heterocyclic compounds containing cyclopropa[a]pyrrolizidine-2,3′-oxindole and 3-spiro[3-azabicyclo[3.1.0]-hexane]oxindole frameworks were synthesized studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), acute T cell leukemia (Jurkat), melanoma (Sk-mel-2) breast cancer (MCF-7) as well mouse colon (CT26) lines. Methods: Cell proliferation was evaluated by MTS assay. Confocal microscopy used to study actin cytoskeleton structure motility. cycle analysis flow cytometry. Results: It found that 4, 8, 18 24 showed the Jurkat, K-562, HeLa Sk-mel-2 lines with IC50 ranging from 2 10 μM (72 h). Evaluation impact on progression tested achieved significant cell-cycle perturbation a higher accumulation cells SubG1 G0/G1 phases cycle, comparison negative control. I Incubation led disappearance stress fibers (granular distributed diffusely cytoplasm up 38% treated cells) changes number filopodia-like deformations (reduced 93% control 64% after treatment). The even greater: granular 90% while reduced 23%. scratch test performed line these did not fill scratched strip lose ability move under treatment. Conclusions: obtained results support antitumor effect spiro-compounds encourage extension this order improve anticancer reduce toxicological risks.

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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Diastereoselective 1,3-dipolar cycloaddition of cyclopropenes to acenaphthenequinone azomethine ylides

Tetrahedron, Год журнала: 2023, Номер 151, С. 133792 - 133792

Опубликована: Дек. 20, 2023

Язык: Английский

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Cycloadditions of 4-Alkenyl-2-aminothiazoles with Nitroalkenes in the Formal Synthesis of Pramipexole: An Experimental and Computational Study

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(17), С. 12049 - 12061

Опубликована: Авг. 19, 2024

4-Alkenyl-2-dialkylaminothiazoles act as in–out dienes in [4 + 2] cycloaddition reactions with nitroalkenes, furnishing 2-amino-6-nitro-4,5,6,7-tetrahydrobenzothiazoles moderate to good yields, accompanied by a subsequent 1,3-H migration. These transformations proceed exquisite site-, regio-, and diastereoselectivity. This strategy is further enriched revealing novel route for pramipexole synthesis. The examination of the potential energy surfaces associated four possible reaction pathways Diels–Alder (relative approach diene–dienophile endo/exo nitro group) not only aligns experimental observations but also unveils key mechanistic insights. Specifically, computational analyses uncover favored pathway yielding 6-nitro-4,5,6,7-tetrahydrobenzothiazoles, some instances proceeding through two-step mechanism involving tandem sequence chemical processes, influence various factors such dienophile structure mode group. Additionally, stabilization exo-transition states, particularly facilitated phenyl substitution dienophile, highlighted. Asynchronicity, dipole moment, other parameters indicative polar character characterize these reactions. Conceptual DFT calculations underscore pivotal role 1,3-thiazole ring enhancing dienic activation dictating regioselectivity, emphasizing interactions between C5 thiazole nucleus Cβ atom nitroalkenes.

Язык: Английский

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[3+2]‐Cycloaddition Reactions of gem‐Difluorocyclopropenes with Azomethine Ylides – Access to Novel Fluorinated Scaffolds

Chemistry - A European Journal, Год журнала: 2023, Номер 29(54)

Опубликована: Июль 4, 2023

Abstract The introduction of fluorinated moieties into drugs as well the increase their overall three‐dimensionality have become key strategies amongst medicinal chemists to generate sets compounds with favorable drug‐like properties. However, cyclopropane ring systems which combines both is not widely exploited date. This paper reports synthetic exploiting reactivity gem‐ difluorocyclopropenes in dipolar cycloaddition reactions azomethine ylides afford new fluorine‐containing 3‐azabicyclo[3.1.0]hexanes. In addition, unexpected formation complex trifluorinated scaffolds arising from proline esters and highlighted along computational studies elucidate underlying mechanism. study presents avenues towards pharmaceutically relevant 3‐azabicyclo[3.1.0]hexanes that are accessible via robust short sequences.

Язык: Английский

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Organic Chemistry in Russian Universities: Achievements of recent years

Журнал органической химии, Год журнала: 2024, Номер 60(2-3)

Опубликована: Дек. 27, 2024

Язык: Английский

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