Efficient synthesis of seven-membered Aza-sultams: Heterofused amino-1,2,4-thiadiazepine dioxides

Hys, Vasyl Y.; Milokhov, Demyd S.; Keda, Tetiana Ye.; Omelchenko, Irina V.; Konovalova, Irina S.; Shishkina, Svitlana V.; Volovenko, Yulian M.

doi:10.1016/j.tet.2021.132149

Cited by 6 publications

(3 citation statements)

References 91 publications

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“…Recently we have reported the synthesis of carbo-and heterofused 7-membered (aza)sultams [60][61][62] trough the CSIС (Carbanion-mediated Sulfonate (Sulfonamide) Intermolecular Coupling (Intramolecular Cyclization)) [63][64][65][66][67][68] reaction strategy. In present work we applied this strategy toward the synthesis of sp 3 -enriched ε-sultams.…”

Section: Chemistrymentioning

confidence: 99%

Design, synthesis, chemical and biological evaluation of 2,5,5-trisubstituted-1,2-thiazepan-6-one 1,1-dioxides

Milokhov,

Pomalin,

Balabushko

et al. 2023

Preprint

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In this article, we designed and synthesized a series of novel 2,5,5-trisubstituted (including spirocyclic) 1,2-thiazepan-6-one 1,1-dioxides (put simply, γ,γ-disubstituted β-keto ε-sultams), prepared a number of derivatives and evaluated their cytotoxic activity against MDA-MB-231 breast cancer cell line. In particular, alkylation of N-monosubstituted methanesulfonamides with α,α-disubstituted β-halogenated esters (including cyclic representatives) afforded the corresponding N-mesylated β-amino acid esters. The latters were involved in CSIC (Carbanion-mediated Sulfonamide Intramolecular Cyclization) reaction to give the target γ,γ-disubstituted β-keto ε-sultams (including spirocyclic representatives) in synthetically useful yields. This class of compounds can be considered as valuable building blocks since they possess carbonyl functionality and an EWG-activated methylene group capable of further functionalization. For instance, the condensation with DMFDMA afforded the corresponding α-dimethylaminomethylidene derivatives ‒ the direct precursors for the heterocyclization reactions. Their treatment with hydrazine hydrate or guanidine hydrochloride provided the corresponding pyrazolo- and pyrimidofused ε-sultams. Despite the prepared β-keto ε-sultams showing weak cytotoxicity against the MDA-MB-231 breast cancer cell line, their pyrazolofused derivatives appeared perspective pharmacological templates with stable cytotoxic effects. Moreover, β-keto ε-sultams and their heterofused derivatives form the water-soluble conjugates with branched polymers based on dextran-polyacrylamide (D-PAA) that can be used as the transport module for the targeted drug delivery in biological media.

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Section: Chemistrymentioning

confidence: 99%

Design, synthesis, chemical and biological evaluation of 2,5,5-trisubstituted-1,2-thiazepan-6-one 1,1-dioxides

Milokhov,

Pomalin,

Balabushko

et al. 2023

Preprint

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“…Tricyclic imidazoles and their 7-membered ring derivatives, as one of the most important classes of structural motifs, − are widely present in numerous biologically active material molecules. Owing to their significance, the synthesis of tricyclic imidazoles and their 7-membered ring derivatives − has attracted widespread attention, and extensive effort has been devoted to the development of new methodologies. − Among a large number of strategies, direct construction of a 7-membered ring via C7–H cyclization of benzimidazoles with alkenes would provide a more straightforward, atom- and step-economic access to tricyclic imidazoles from more easily accessible substrates. However, over the past few decades, transition metal-catalyzed C–H cyclization − for medium-ring synthesis has been a challenging goal.…”

Section: Introductionmentioning

confidence: 99%

DFT Study on Mechanism of Ni–Al Bimetallic-Catalyzed C–H Cyclization to Construct Tricyclic Imidazoles: Roles of NHC Ligand and AlMe₃

Zhang,

Li,

Shang

et al. 2024

J. Org. Chem.

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The mechanism of the Ni–Al bimetallic-catalyzed C–H cyclization to construct tricyclic imidazoles is investigated using density functional theory calculations. The calculation result shows that the reaction mechanism involves sequential steps of substrate coordination, ligand-to-ligand hydrogen transfer (LLHT), and C–C reductive elimination to produce the final product tricyclic imidazole. The LLHT step is calculated to be the rate-determining step. The oxidative addition of the benzimidazole C–H bond to the Ni center and the insertion of the alkene into the Ni–H bond occur concertedly in the LLHT step. The effects of N-heterocyclic carbene (NHC) ligands and AlMe3 on the reactivity and regioselectivity were also analyzed. These calculation results shed light on some ambiguous suggestions from experiments.

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“…In particular, the derivatives of 2-cyanoindoles gained considerable attention in recent years because of their great importance in biological sciences, and they are also of interest thanks to this nitrile function [10][11][12]. The 2-cyanoindole unit is an example of structural motif building blocks and effective precursors for the synthesis of various indole-fused polycycles [13][14][15][16][17][18][19], substituted 2-cyanoindoles [20][21][22][23][24], addition to nitriles [25,26] and indole heterocycle substitution [27,28]. These compounds exhibit a wide range of biological activities (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of New Highly Functionalized 1H-Indole-2-carbonitriles via Cross-Coupling Reactions

et al. 2021

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An approach for the preparation of polysubstituted indole-2-carbonitriles through a cross-coupling reaction of compounds 1-(but-2-ynyl)-1H-indole-2-carbonitriles and 1-benzyl-3-iodo-1H-indole-2-carbonitriles is described. The reactivity of indole derivatives with iodine at position 3 was studied using cross-coupling reactions. The Sonogashira, Suzuki–Miyaura, Stille and Heck cross-couplings afforded a variety of di-, tri- and tetra-substituted indole-2-carbonitriles.

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Efficient synthesis of seven-membered Aza-sultams: Heterofused amino-1,2,4-thiadiazepine dioxides

Cited by 6 publications

References 91 publications

Design, synthesis, chemical and biological evaluation of 2,5,5-trisubstituted-1,2-thiazepan-6-one 1,1-dioxides

Design, synthesis, chemical and biological evaluation of 2,5,5-trisubstituted-1,2-thiazepan-6-one 1,1-dioxides

DFT Study on Mechanism of Ni–Al Bimetallic-Catalyzed C–H Cyclization to Construct Tricyclic Imidazoles: Roles of NHC Ligand and AlMe₃

Synthesis of New Highly Functionalized 1H-Indole-2-carbonitriles via Cross-Coupling Reactions

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Efficient synthesis of seven-membered Aza-sultams: Heterofused amino-1,2,4-thiadiazepine dioxides

Cited by 6 publications

References 91 publications

Design, synthesis, chemical and biological evaluation of 2,5,5-trisubstituted-1,2-thiazepan-6-one 1,1-dioxides

Design, synthesis, chemical and biological evaluation of 2,5,5-trisubstituted-1,2-thiazepan-6-one 1,1-dioxides

DFT Study on Mechanism of Ni–Al Bimetallic-Catalyzed C–H Cyclization to Construct Tricyclic Imidazoles: Roles of NHC Ligand and AlMe3

Synthesis of New Highly Functionalized 1H-Indole-2-carbonitriles via Cross-Coupling Reactions

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DFT Study on Mechanism of Ni–Al Bimetallic-Catalyzed C–H Cyclization to Construct Tricyclic Imidazoles: Roles of NHC Ligand and AlMe₃