International Journal of Molecular Sciences

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23 pages, 3125 KiB

Open AccessArticle

Selenium Dibromide Click Chemistry: The Efficient Synthesis of Novel Selenabicyclo[3.3.1]nonene-2 and -nonane Derivatives

by Maxim V. Musalov, Svetlana V. Amosova and Vladimir A. Potapov

Int. J. Mol. Sci. 2023, 24(24), 17485; https://doi.org/10.3390/ijms242417485 - 14 Dec 2023

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Abstract

Highly efficient and convenient methods for the preparation of 35 novel derivatives of 9-selenabicyclo[3.3.1]nonane and 9-selenabicyclo[3.3.1]nonene-2 in high yields based on the adduct of the transannular addition of SeBr₂ to 1,5-cyclooctadiene were developed. The methods for the amination of the adduct made [...] Read more.

Highly efficient and convenient methods for the preparation of 35 novel derivatives of 9-selenabicyclo[3.3.1]nonane and 9-selenabicyclo[3.3.1]nonene-2 in high yields based on the adduct of the transannular addition of SeBr₂ to 1,5-cyclooctadiene were developed. The methods for the amination of the adduct made it possible to obtain both diamino selenabicyclo[3.3.1]nonane derivatives and their dihydrobromide salts in one step in 88–98% yields. The methods meet the criteria of click chemistry. Compounds with high glutathione peroxidase mimetic activity were found among water-soluble dihydrobromide salts. The selective reaction of 2,6-dibromo-9-selenabicyclo[3.3.1]nonane with acetonitrile to form 6-bromo-9-selenabicyclo[3.3.1]nonene-2 was discovered. The latter compound served as a promising starting material to give rise to the new class of selenabicyclo[3.3.1]nonene-2 derivatives, e.g., 6-alkoxy-9-selenabicyclo[3.3.1]nonenes were obtained in 94–99% yields. Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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16 pages, 4734 KiB

Open AccessArticle

5-Nitroisoxazoles in S_NAr Reactions: A Novel Chemo- and Regioselective Approach to Isoxazole-Based Bivalent Ligands of AMPA Receptors

by Dmitry A. Vasilenko, Nadezhda S. Temnyakova, Sevastian E. Dronov, Eugene V. Radchenko, Yuri K. Grishin, Alexey V. Gabrel’yan, Vladimir L. Zamoyski, Vladimir V. Grigoriev, Elena B. Averina and Vladimir A. Palyulin

Int. J. Mol. Sci. 2023, 24(22), 16135; https://doi.org/10.3390/ijms242216135 - 9 Nov 2023

Cited by 2 | Viewed by 1094

Abstract

An efficient regioselective approach to novel functionalized bis(isoxazoles) with a variety of aromatic and aliphatic linkers was elaborated, based on the heterocyclization reaction of electrophilic alkenes under the treatment with tetranitromethane-triethylamine complex affording 3-EWG-5-nitroisoxazoles. The subsequent S_NAr reactions of 5-nitroisoxazoles with [...] Read more.

An efficient regioselective approach to novel functionalized bis(isoxazoles) with a variety of aromatic and aliphatic linkers was elaborated, based on the heterocyclization reaction of electrophilic alkenes under the treatment with tetranitromethane-triethylamine complex affording 3-EWG-5-nitroisoxazoles. The subsequent S_NAr reactions of 5-nitroisoxazoles with various O,O-, N,N- and S,S-bis(nucleophiles) provide a wide range of bis(isoxazole) derivatives in good isolated yields. Employing an elaborated method, a series of novel bis(3-EWG-isoxazoles) as the promising allosteric modulators of AMPA receptors were designed and synthesized. The effect of the compounds on the kainate-induced currents was studied in the patch clamp experiments, revealing modulator properties for several of them. The best positive modulator potency was found for dimethyl 5,5′-(ethane-1,2-diylbis(sulfanediyl))bis(isoxazole-3-carboxylate), which potentiated the kainate-induced currents in a wide concentration range (10⁻¹²–10⁻⁶ M) with maximum potentiation of 77% at 10⁻¹⁰ M. The results were rationalized using molecular docking and molecular dynamics simulations of modulator complexes with the dimeric ligand-binding domain of the GluA2 AMPA receptor. The predicted physicochemical, ADMET, and PAINS properties confirmed that the AMPA receptor modulators based on the bis(isoxazole) scaffold may serve as potential lead compounds for the development of neuroprotective drugs. Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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23 pages, 6095 KiB

Open AccessArticle

Benzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole) and Its Bromo Derivatives: Molecular Structure and Reactivity

by Timofey N. Chmovzh, Daria A. Alekhina, Timofey A. Kudryashev, Rinat R. Aysin, Alexander A. Korlyukov and Oleg A. Rakitin

Int. J. Mol. Sci. 2023, 24(10), 8835; https://doi.org/10.3390/ijms24108835 - 16 May 2023

Cited by 1 | Viewed by 2329

Abstract

Benzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole) (isoBBT) is a new electron-withdrawing building block that can be used to obtain potentially interesting compounds for the synthesis of OLEDs and organic solar cells components. The electronic structure and delocalization in benzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole), 4-bromobenzo[1,2- [...] Read more.

Benzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole) (isoBBT) is a new electron-withdrawing building block that can be used to obtain potentially interesting compounds for the synthesis of OLEDs and organic solar cells components. The electronic structure and delocalization in benzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole), 4-bromobenzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole), and 4,8-dibromobenzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole) were studied using X-ray diffraction analysis and ab initio calculations by EDDB and GIMIC methods and were compared to the corresponding properties of benzo[1,2-c:4,5-c′]bis[1,2,5]thiadiazole (BBT). Calculations at a high level of theory showed that the electron affinity, which determines electron deficiency, of isoBBT was significantly smaller than that of BBT (1.09 vs. 1.90 eV). Incorporation of bromine atoms improves the electrical deficiency of bromobenzo-bis-thiadiazoles nearly without affecting aromaticity, which increases the reactivity of these compounds in aromatic nucleophilic substitution reactions and, on the other hand, does not reduce the ability to undergo cross-coupling reactions. 4-Bromobenzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole) is an attractive object for the synthesis of monosubstituted isoBBT compounds. The goal to find conditions for the selective substitution of hydrogen or bromine atoms at position 4 in order to obtain compounds containing a (het)aryl group in this position and to use the remaining unsubstituted hydrogen or bromine atoms to obtain unsymmetrically substituted isoBBT derivatives, potentially interesting compounds for organic photovoltaic components, was not set before. Nucleophilic aromatic and cross-coupling reactions, along with palladium-catalyzed C-H direct arylation reactions for 4-bromobenzo[1,2-d:4,5-d′]bis([1,2,3]thiadiazole), were studied and selective conditions for the synthesis of monoarylated derivatives were found. The observed features of the structure and reactivity of isoBBT derivatives may be useful for building organic semiconductor-based devices. Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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11 pages, 2055 KiB

Open AccessArticle

Asymmetric Organocatalytic Mannich Reaction in the Synthesis of Hybrid Isoindolinone-Pyrazole and Isoindolinone-Aminal from Functionalized α-Amidosulfone

by Antonia Di Mola, Felice De Piano, Lorenzo Serusi, Giovanni Pierri, Laura Palombi and Antonio Massa

Int. J. Mol. Sci. 2023, 24(6), 5783; https://doi.org/10.3390/ijms24065783 - 17 Mar 2023

Cited by 1 | Viewed by 1618

Abstract

The investigation of the reactivity of an α-amido sulfone derived from 2-formyl benzoate under organocatalytic conditions in the presence of acetylacetone allowed the synthesis of a new heterocyclic hybrid isoindolinone-pyrazole with high enantiomeric excess. Dibenzylamine was also used as a nucleophile to afford [...] Read more.

The investigation of the reactivity of an α-amido sulfone derived from 2-formyl benzoate under organocatalytic conditions in the presence of acetylacetone allowed the synthesis of a new heterocyclic hybrid isoindolinone-pyrazole with high enantiomeric excess. Dibenzylamine was also used as a nucleophile to afford an isoindolinone with aminal substituent in 3-position in suitable selectivity. The use of Takemoto’s bifunctional organocatalyst not only led to observed enantioselectivity but was also important in accomplishing the cyclization step in both cases. Notably, this catalytic system proved to be particularly effective in comparison to widely used phase transfer catalysts. Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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16 pages, 1881 KiB

Open AccessArticle

Contributing to Biochemistry and Optoelectronics: Pyrrolo[1′,2′:2,3]imidazo[1,5-a]indoles and Cyclohepta[4,5]pyrrolo[1,2-c]pyrrolo[1,2-a]imidazoles via [3+2] Annulation of Acylethynylcycloalka[b]pyrroles with Δ¹-Pyrrolines

by Ludmila A. Oparina, Nikita A. Kolyvanov, Igor A. Ushakov, Lina P. Nikitina, Olga V. Petrova, Lyubov N. Sobenina, Konstantin B. Petrushenko and Boris A. Trofimov

Int. J. Mol. Sci. 2023, 24(4), 3404; https://doi.org/10.3390/ijms24043404 - 8 Feb 2023

Cited by 5 | Viewed by 3011

Abstract

Available pyrrolylalkynones with tetrahydroindolyl, cycloalkanopyrrolyl, and dihydrobenzo[g]indolyl moieties, acylethynylcycloalka[b]pyrroles, are readily annulated with Δ¹-pyrrolines (MeCN/THF, 70 °C, 8 h) to afford a series of novel pyrrolo[1′,2′:2,3]imidazo[1,5-a]indoles and cyclohepta[4,5]pyrrolo[1,2-c]pyrrolo[1,2-a]imidazoles functionalized with an [...] Read more.

Available pyrrolylalkynones with tetrahydroindolyl, cycloalkanopyrrolyl, and dihydrobenzo[g]indolyl moieties, acylethynylcycloalka[b]pyrroles, are readily annulated with Δ¹-pyrrolines (MeCN/THF, 70 °C, 8 h) to afford a series of novel pyrrolo[1′,2′:2,3]imidazo[1,5-a]indoles and cyclohepta[4,5]pyrrolo[1,2-c]pyrrolo[1,2-a]imidazoles functionalized with an acylethenyl group in up to an 81% yield. This original synthetic approach contributes to the arsenal of chemical methods promoting drug discovery. Photophysical studies show that some of the synthesized compounds, e.g., benzo[g]pyrroloimidazoindoles, are prospective candidates for TADF emitters of OLED. Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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19 pages, 4474 KiB

Open AccessArticle

The Synthesis and Absolute Configuration of Enantiomeric Pure (R)- and (S)-3-(piperidin-3-yl)-1H-Indole Derivatives

by Marek Król, Grzegorz Ślifirski, Jerzy Kleps, Piotr Podsadni, Ilona Materek, Anna E. Kozioł and Franciszek Herold

Int. J. Mol. Sci. 2023, 24(1), 517; https://doi.org/10.3390/ijms24010517 - 28 Dec 2022

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Abstract

This article describes the synthesis of new chiral 3-(piperidin-3-yl)-1H-indole derivatives (R)-10a-c and (S)-11a-c from the corresponding diastereomers: (3R, 2R) and (3S, 2R)-2-[3-(1H-indol-3-yl)-1-piperidyl]-2-phenyl-acetamides (3R, 2R)-4a, (3R, 2R)-6b, (3R, 2R)-8c and (3S, 2R)-5a, (3S, 2R)-7b, (3S, 2R)-9c. Diastereomers were obtained by N-alkylation of derivatives [...] Read more.

This article describes the synthesis of new chiral 3-(piperidin-3-yl)-1H-indole derivatives (R)-10a-c and (S)-11a-c from the corresponding diastereomers: (3R, 2R) and (3S, 2R)-2-[3-(1H-indol-3-yl)-1-piperidyl]-2-phenyl-acetamides (3R, 2R)-4a, (3R, 2R)-6b, (3R, 2R)-8c and (3S, 2R)-5a, (3S, 2R)-7b, (3S, 2R)-9c. Diastereomers were obtained by N-alkylation of derivatives of racemic 3-(piperidin-3-yl)-1H-indoles 1a-c using (S)-2-(4-toluenesulfonyloxy)-phenylacetic amide (S)–II. The same method was applied to obtain (3R, 2S)-methyl-2-[3-(1H-indole-3-yl)-1-piperidyl]-2-phenylacetate (3R, 2S)-2a and (3S, 2S)-methyl-2-[3-(1H-indole-3-yl)-1-piperidyl]-2-phenylacetate (3S, 2S)-3a diastereomers by treating amine 1a with (R)-2-(4-toluenesulfonyloxy)-phenylacetic acid methylester (R)-I. Systematic studies via single crystal X-ray crystallography were used to determine the molecular structure of the racemates 1a-c and the absolute configuration of the enantiomers. The solid racemates 1b and 1c were “true racemates” crystallizing in a centrosymmetric space group, while 1a formed a racemic conglomerate of homoenantiomeric crystals. The absolute configuration was determined for the enantiomeric pairs (R)-10a/(S)-11a, (R)-10b/(S)-11b, and (R)-12c/(S)-13c, as well as for (3S,2S)-3a. Spectra of ¹H, ¹³CNMR, HPLC, and HRMS for diastereomers and enantiomers were consistent with the determined structures. Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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Review

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24 pages, 5725 KiB

Open AccessReview

Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review

by Rida Noor, Ameer Fawad Zahoor, Asim Mansha, Samreen Gul Khan, Atta Ul Haq, Sajjad Ahmad, Sami A. Al-Hussain, Ali Irfan and Magdi E. A. Zaki

Int. J. Mol. Sci. 2023, 24(7), 6692; https://doi.org/10.3390/ijms24076692 - 3 Apr 2023

Cited by 4 | Viewed by 2697

Abstract

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size [...] Read more.

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size carbo- and heterocycles involving lactams, lactone, azepine and azulene derivatives via ring expansion of six-membered carbo- and heterocycles that have been reported from 2007–2022. Numerous rearrangement and cycloaddition reactions involving Tiffeneau–Demjanov rearrangement, Aza–Claisen rearrangement, Schmidt rearrangement, Beckmann rearrangement, etc., have been described in this regard. Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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22 pages, 7646 KiB

Open AccessReview

Bio-Derived Furanic Compounds with Natural Metabolism: New Sustainable Possibilities for Selective Organic Synthesis

by Leonid V. Romashov, Fedor A. Kucherov, Kirill S. Kozlov and Valentine P. Ananikov

Int. J. Mol. Sci. 2023, 24(4), 3997; https://doi.org/10.3390/ijms24043997 - 16 Feb 2023

Cited by 2 | Viewed by 2532

Abstract

Biomass-derived C6-furanic compounds have become the cornerstone of sustainable technologies. The key feature of this field of chemistry is the involvement of the natural process only in the first step, i.e., the production of biomass by photosynthesis. Biomass-to-HMF (5-hydroxymethylfurfural) conversion and further transformations [...] Read more.

Biomass-derived C6-furanic compounds have become the cornerstone of sustainable technologies. The key feature of this field of chemistry is the involvement of the natural process only in the first step, i.e., the production of biomass by photosynthesis. Biomass-to-HMF (5-hydroxymethylfurfural) conversion and further transformations are carried out externally with the involvement of processes with poor environmental factors (E-factors) and the generation of chemical wastes. Due to widespread interest, the chemical conversion of biomass to furanic platform chemicals and related transformations are thoroughly studied and well-reviewed in the current literature. In contrast, a novel opportunity is based on an alternative approach to consider the synthesis of C6-furanics inside living cells using natural metabolism, as well as further transformations to a variety of functionalized products. In the present article, we review naturally occurring substances containing C6-furanic cores and focus on the diversity of C6-furanic derivatives, occurrence, properties and synthesis. From the practical point of view, organic synthesis involving natural metabolism is advantageous in terms of sustainability (sunlight-driven as the only energy source) and green nature (no eco-persisted chemical wastes). Full article

(This article belongs to the Special Issue New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis)

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