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13 pages, 1887 KiB

Open AccessArticle

3-Nitroindoles Serving as N-Centered Nucleophiles for Aza-1,6-Michael Addition to para-Quinone Methides

by Jian-Qiang Zhao, Wen-Jie Wang, Shun Zhou, Qi-Lin Xiao, Xi-Sha Xue, Yan-Ping Zhang, Yong You, Zhen-Hua Wang and Wei-Cheng Yuan

Molecules 2023, 28(14), 5529; https://doi.org/10.3390/molecules28145529 - 20 Jul 2023

Cited by 2 | Viewed by 1306

Abstract

An unprecedented N-alkylation of 3-nitroindoles with para-quinone methides was developed for the first time. Using potassium carbonate as the base, a wide range of structurally diverse N-diarylmethylindole derivatives were obtained with moderated to good yields via the protection group migration/ [...] Read more.

An unprecedented N-alkylation of 3-nitroindoles with para-quinone methides was developed for the first time. Using potassium carbonate as the base, a wide range of structurally diverse N-diarylmethylindole derivatives were obtained with moderated to good yields via the protection group migration/aza-1,6-Michael addition sequences. The reaction process was also demonstrated by control experiments. Different from the previous advances where 3-nitrodoles served as electrophiles trapping by various nucleophiles, the reaction herein is featured that 3-nitrodoles is defined with latent N-centered nucleophiles to react with ortho-hydrophenyl p-QMs for construction of various N-diarylmethylindoles. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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10 pages, 3074 KiB

Open AccessCommunication

Regio- and Stereoselective Switchable Synthesis of (E)- and (Z)-N-Carbonylvinylated Pyrazoles

by Xue Zhang, Zheyu Zhang, Haifeng Yu and Guangbo Che

Molecules 2023, 28(11), 4347; https://doi.org/10.3390/molecules28114347 - 25 May 2023

Cited by 2 | Viewed by 1134

Abstract

Regio- and stereoselective switchable synthesis of (E)- and (Z)-N-carbonylvinylated pyrazoles is first developed by using the Michael addition reaction of pyrazoles and conjugated carbonyl alkynes. Ag₂CO₃ plays a key role in the switchable synthesis [...] Read more.

Regio- and stereoselective switchable synthesis of (E)- and (Z)-N-carbonylvinylated pyrazoles is first developed by using the Michael addition reaction of pyrazoles and conjugated carbonyl alkynes. Ag₂CO₃ plays a key role in the switchable synthesis of (E)- and (Z)-N-carbonylvinylated pyrazoles. Ag₂CO₃-free reactions lead to thermodynamically stable (E)-N-carbonylvinylated pyrazoles in excellent yields whereas reactions with Ag₂CO₃ give (Z)-N-carbonylvinylated pyrazoles in good yields. It is noteworthy that (E)- or (Z)-N¹-carbonylvinylated pyrazoles are obtained with high regioselectivity when asymmetrically substituted pyrazoles react with conjugated carbonyl alkynes. The method can also extend to the gram scale. A plausible mechanism is proposed on the basis of the detailed studies, wherein Ag⁺ acts as coordination guidance. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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14 pages, 1834 KiB

Open AccessArticle

Synthesis and Structure–Activity Analysis of Novel Potential Antifungal Cyclotryptamine Alkaloid Derivatives

by Yazhou Yang, Yujie Zhou, Qiaoju Jiang, Yi Tan, Wenbin Wu, Ke Han, Rui Zhu and Shaojun Zheng

Molecules 2023, 28(6), 2617; https://doi.org/10.3390/molecules28062617 - 13 Mar 2023

Cited by 2 | Viewed by 1537

Abstract

A total of 39 novel cyclotryptamine alkaloid derivatives were prepared from 2-(1H-indol-3-yl) acetonitrile. The prepared compounds were evaluated against six plant pathogen fungi. Bioassay results revealed that most of the compounds displayed higher in vitro antifungal activities than the positive control. Notably, compound [...] Read more.

A total of 39 novel cyclotryptamine alkaloid derivatives were prepared from 2-(1H-indol-3-yl) acetonitrile. The prepared compounds were evaluated against six plant pathogen fungi. Bioassay results revealed that most of the compounds displayed higher in vitro antifungal activities than the positive control. Notably, compound b2 displayed the broadest and most effective activity among the tested cyclotryptamine alkaloid derivatives and might be a novel potential leading compound for further development as an antifungal agent. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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8 pages, 934 KiB

Open AccessArticle

2-Phenylpyridine Derivatives: Synthesis and Insecticidal Activity against Mythimna separata, Aphis craccivora, and Tetranychus cinnabarinus

by Wenliang Zhang, Jingjing Chen and Xiaohua Du

Molecules 2023, 28(4), 1567; https://doi.org/10.3390/molecules28041567 - 6 Feb 2023

Cited by 3 | Viewed by 1941

Abstract

The increase in the insecticide resistance of pests, such as Mythimna separata, Aphis craccivora Koch, and Tetranychus cinnabarinus, necessitates the development of new heterocyclic compounds with high insecticidal activity. A series of novel 2-phenylpyridine derivatives containing N-phenylbenzamide moieties were [...] Read more.

The increase in the insecticide resistance of pests, such as Mythimna separata, Aphis craccivora Koch, and Tetranychus cinnabarinus, necessitates the development of new heterocyclic compounds with high insecticidal activity. A series of novel 2-phenylpyridine derivatives containing N-phenylbenzamide moieties were designed and synthesised with Suzuki–Miyaura cross-coupling, nucleophilic substitution, and amidation reactions. The reaction conditions in each step are mild, and the product is easy to separate (yield is about 85%). The structures of the compounds were characterised using ¹H and ¹³C NMR spectroscopy and HRMS. Moreover, the insecticidal activity of the compounds was analysed using the leaf dipping method. The compounds 5a, 5d, 5g, 5h, and 5k at 500 mg/L exhibited 100% inhibition against Mythimna separata. Therefore, the 2-phenylpyridine moieties have the potential to lead to the discovery of novel and effective insecticides. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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18 pages, 1429 KiB

Open AccessArticle

Synthesis, Characterization and Biological Evaluation of Benzothiazole–Isoquinoline Derivative

by Weihua Liu, Donghai Zhao, Zhiwen He, Yiming Hu, Yuxia Zhu, Lingjian Zhang, Lianhai Jin, Liping Guan and Sihong Wang

Molecules 2022, 27(24), 9062; https://doi.org/10.3390/molecules27249062 - 19 Dec 2022

Cited by 3 | Viewed by 2456

Abstract

Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi–target–directed ligands (MTDLs), we synthesized a series of (R)–N–(benzo[d]thiazol–2–yl)–2–(1–phenyl–3,4–dihydroisoquinolin–2(1H)–yl) acetamides with substituted benzothiazoles and [...] Read more.

Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi–target–directed ligands (MTDLs), we synthesized a series of (R)–N–(benzo[d]thiazol–2–yl)–2–(1–phenyl–3,4–dihydroisoquinolin–2(1H)–yl) acetamides with substituted benzothiazoles and (S)–1–phenyl–1,2,3,4–tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO–B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b–4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO–B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood–brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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15 pages, 1668 KiB

Open AccessArticle

Condensation of 4-Tert-butyl-2,6-dimethylbenzenesulfonamide with Glyoxal and Reaction Features: A New Process for Symmetric and Asymmetric Aromatic Sulfones

by Artyom E. Paromov, Sergey V. Sysolyatin and Irina A. Shchurova

Molecules 2022, 27(22), 7793; https://doi.org/10.3390/molecules27227793 - 12 Nov 2022

Cited by 4 | Viewed by 1655

Abstract

The synthesis of substituted aza- and oxaazaisowurtzitanes via direct condensation is challenging. The selection of starting ammonia derivatives is very limited. The important step in developing alternative synthetic routes to these compounds is a detailed study on their formation process. Here, we explored [...] Read more.

The synthesis of substituted aza- and oxaazaisowurtzitanes via direct condensation is challenging. The selection of starting ammonia derivatives is very limited. The important step in developing alternative synthetic routes to these compounds is a detailed study on their formation process. Here, we explored an acid-catalyzed condensation between 4-tert-butyl-2,6-dimethylbenzenesulfonamide and glyoxal in aqueous H₂SO₄, aqueous acetonitrile and acetone, and established some new processes hindering the condensation. In particular, an irreversible rearrangement of the condensation intermediate was found to proceed and be accompanied by the 1,2-hydride shift and by the formation of symmetric disulfanes and sulfanes. It has been shown for the first time that aldehydes may act as a reducing agent when disulfanes are generated from aromatic sulfonamides, as is experimentally proved. The condensation between 4-tert-butyl-2,6-dimethylbenzenesulfonamide and formaldehyde resulted in 1,3,5-tris((4-(tert-butyl)-2,6-dimethylphenyl)sulfonyl)-1,3,5-triazinane. It was examined if diimine could be synthesized from 4-tert-butyl-2,6-dimethylbenzenesulfonamide and glyoxal by the most common synthetic procedures for structurally similar imines. It has been discovered for the first time that the Friedel–Crafts reaction takes place between sulfonamide and the aromatic compound. A new synthetic strategy has been suggested herein that can reduce the stages in the synthesis of in-demand organic compounds of symmetric and asymmetric aromatic sulfones via the Brønsted acid-catalyzed Friedel–Crafts reaction, starting from aromatic sulfonamides and arenes activated towards an electrophilic attack. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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8 pages, 1337 KiB

Open AccessArticle

Synthesis of Novel Pyrazole Derivatives Containing Phenylpyridine Moieties with Herbicidal Activity

by Zengfei Cai, Wenliang Zhang, Zhongjie Yan and Xiaohua Du

Molecules 2022, 27(19), 6274; https://doi.org/10.3390/molecules27196274 - 23 Sep 2022

Cited by 5 | Viewed by 2117

Abstract

To discover new compounds with favorable herbicidal activity, a range of phenylpyridine moiety-containing pyrazole derivatives were designed, synthesized, and identified via NMR and HRMS. Their herbicidal activities against six species of weeds were evaluated in a greenhouse via both pre- and post-emergence treatments [...] Read more.

To discover new compounds with favorable herbicidal activity, a range of phenylpyridine moiety-containing pyrazole derivatives were designed, synthesized, and identified via NMR and HRMS. Their herbicidal activities against six species of weeds were evaluated in a greenhouse via both pre- and post-emergence treatments at 150 g a.i./hm². The bioassay revealed that a few compounds exhibited moderate herbicidal activities against Digitaria sanguinalis, Abutilon theophrasti, and Setaria viridis in post-emergence treatment. For instance, compounds 6a and 6c demonstrated 50% inhibition activity against Setaria viridis, which was slightly superior to pyroxasulfone. Thus, compounds 6a and 6c may serve as the new possible leading compounds for the discovery of post-emergence herbicides. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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19 pages, 16937 KiB

Open AccessArticle

Application of meso-CF₃-Fluorophore BODIPY with Phenyl and Pyrazolyl Substituents for Lifetime Visualization of Lysosomes

by Irina S. Trukhan, Denis N. Tomilin, Nataliya N. Dremina, Lyubov N. Sobenina, Michael G. Shurygin, Konstantin B. Petrushenko, Igor K. Petrushenko, Boris A. Trofimov and Irina A. Shurygina

Molecules 2022, 27(15), 5018; https://doi.org/10.3390/molecules27155018 - 7 Aug 2022

Cited by 5 | Viewed by 1947

Abstract

A bright far-red emitting unsymmetrical meso-CF₃-BODIPY fluorescent dye with phenyl and pyrazolyl substituents was synthesized by condensation of trifluoropyrrolylethanol with pyrazolyl-pyrrole, with subsequent oxidation and complexation of the formed dipyrromethane. This BODIPY dye exhibits optical absorption at λ_ab ≈ [...] Read more.

A bright far-red emitting unsymmetrical meso-CF₃-BODIPY fluorescent dye with phenyl and pyrazolyl substituents was synthesized by condensation of trifluoropyrrolylethanol with pyrazolyl-pyrrole, with subsequent oxidation and complexation of the formed dipyrromethane. This BODIPY dye exhibits optical absorption at λ_ab ≈ 610–620 nm and emission at λ_em ≈ 640–650 nm. The BODIPY was studied on Ehrlich carcinoma cells as a lysosome-specific fluorescent dye that allows intravital staining of cell structures with subsequent real-time monitoring of changes occurring in the cells. It was also shown that the rate of uptake by cells, the rate of intracellular transport into lysosomes, and the rate of saturation of cells with the dye depend on its concentration in the culture medium. A concentration of 5 μM was chosen as the most suitable BODIPY concentration for fluorescent staining of living cell lysosomes, while a concentration of 100 μM was found to be toxic to Ehrlich carcinoma cells. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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Review

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26 pages, 14387 KiB

Open AccessReview

Recent Advances in DMSO-Based Direct Synthesis of Heterocycles

by Hai-Lei Cui

Molecules 2022, 27(23), 8480; https://doi.org/10.3390/molecules27238480 - 2 Dec 2022

Cited by 17 | Viewed by 3551

Abstract

Besides serving as a low-toxicity, inexpensive and easily accessible solvent, dimethyl sulfoxide (DMSO) has also been extensively used as a versatile reagent for the synthesis of functionalized molecules. Dimethyl sulfoxide can not only be utilized as a carbon source, a sulfur source and [...] Read more.

Besides serving as a low-toxicity, inexpensive and easily accessible solvent, dimethyl sulfoxide (DMSO) has also been extensively used as a versatile reagent for the synthesis of functionalized molecules. Dimethyl sulfoxide can not only be utilized as a carbon source, a sulfur source and an oxygen source, but also be employed as a crucial oxidant enabling various transformations. The past decade has witnessed a large number of impressive achievements on the direct synthesis of heterocycles as well as modifications of heterocyclic compounds by applying DMSO as a reagent. This review summarized the DMSO-based direct heterocycle constructions from 2012 to 2022. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Activity of Nitrogen-Containing Heterocyclic Compounds)

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