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Topical Collection "Heterocyclic Compounds"

A topical collection in Molecules (ISSN 1420-3049). This collection belongs to the section "Organic Chemistry".

Editors

Prof. Dr. Richard A. Bunce
E-Mail Website
Collection Editor
Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078-3071, USA
Interests: heterocycles; antibacterial agents; anticancer agents; enzyme inhibitors; medicinal chemistry; drug discovery; drug development; synthetic methodology
Special Issues and Collections in MDPI journals
Prof. Dr. Philippe Belmont
E-Mail
Collection Editor
School of Pharmacy, University Paris Descartes, UMR CNRS 8638, case 24. 4, avenue de l’Observatoire, 75006 Paris, France
Interests: heterocyclic synthesis; nitrogen-containing heterocycles; methodologies using organic or organometallic reagents; organometallic catalysis; cyclo-isomerization reactions; cyclo-functionalization reactions; benzannulation; aminobenzannulation; pi-acid metal catalysis; silver chemistry; gold chemistry; cobalt chemistry; Pauson-Khand reaction; bioactive compounds; alkaloids; kinases inhibition
Special Issues and Collections in MDPI journals
Prof. Dr. Wim Dehaen
E-Mail Website
Collection Editor
Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium
Interests: organic synthesis; heterocycles; supramolecular chemistry; porphyrin analogues; natural products; helicenes
Special Issues and Collections in MDPI journals

Topical Collection Information

Dear Colleagues,

Heterocyclic compounds are an important class of molecules in organic chemistry, due to their presence in natural products and their use in pharmaceuticals and new materials. Heterocycles are the key to biological activity in many small molecule drugs, due to their ability to hydrogen bond, alter polarity, and modulate lipophilicity at specific sites in the pathogen or host, with the overall effect of inhibiting the biological processes that lead to the programmed progressions of diseases. Similar advantages can be cited in the area of materials chemistry, as heterocycles can impart unique properties to new materials, due to their polarity, solubility, and their electronic and optical properties. In this Molecules Special Issue, entitled "Heterocyclic Compounds", we invite manuscript submissions that focus on the synthesis of natural and unnatural heterocyclic compounds and their potential uses in medicinal and materials chemistry. It is expected that most submissions will focus on nitrogen, oxygen, and sulfur heterocycles, but structures incorporating other heteroatoms will also be considered. Original research articles or reviews that discuss synthetic methodologies for preparing heterocyclic compounds, total synthesis, and structure studies of heterocycle-containing substances, as well as potential new applications to medicinal and materials chemistry, are particularly welcome.

Dr. Richard A. Bunce
Dr. Philippe Belmont
Dr. Wim Dehaen
Prof. Dr. Eugene Babaev
Collection Editors

Manuscript Submission Information

Manuscripts for the topical collection can be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on this website. The topical collection considers regular research articles, short communications and review articles. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page.

Please visit the Instructions for Authors page before submitting a manuscript. The article processing charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs).

Keywords

  • new synthetic approaches to heterocycles
  • synthesis of heterocyclic natural products
  • biologically active heterocycles
  • medicinal studies of heterocycles
  • structure-activity relationships of drugs containing heterocycles
  • new heterocycle-based materials
  • structure-property relationships of materials containing heterocycles
  • heterocycles with unique properties
  • applications of heterocycle-based materials

Published Papers (117 papers)

2021

Jump to: 2020, 2019, 2018, 2017, 2016, 2015

Article
Synthesis of 6-Membered-Ring Fused Thiazine-Dicarboxylates and Thiazole-Pyrimidines via One-Pot Three-Component Reactions
Molecules 2021, 26(18), 5493; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26185493 - 10 Sep 2021
Viewed by 373
Abstract
A facile and efficient one-pot three-component reaction method for the synthesis of thiazine-dicarboxylates is reported. Reaction of an isocyanide and dialkyl acetylenedicarboxylate with 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and an internal nucleophile gave the products in good yields of [...] Read more.
A facile and efficient one-pot three-component reaction method for the synthesis of thiazine-dicarboxylates is reported. Reaction of an isocyanide and dialkyl acetylenedicarboxylate with 2-amino-4H-1,3-thiazin-4-one derivatives containing both an acidic proton and an internal nucleophile gave the products in good yields of 76–85%. The reactivity of dialkyl acetylenedicarboxylates was further tested in the synthesis of thiazole-pyrimidines where a two-component reaction of 2-aminothiazole with dialkyl acetylenedicarboxylates was successfully converted to a more efficient three-component reaction of a thiourea, α-haloketone and dialkyl acetylenedicarboxylate (DMAD/DEtAD) to give thiazole-pyrimidines in good yields of 70–91%. Full article
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Review
4,5,6,7-Tetrahydroindol-4-Ones as a Valuable Starting Point for the Synthesis of Polyheterocyclic Structures
Molecules 2021, 26(15), 4596; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26154596 - 29 Jul 2021
Viewed by 430
Abstract
This review focuses on the synthesis of polyheterocyclic structures with a variety of medicinal and optoelectronic applications, starting from readily available 4,5,6,7-tetrahydroindol-4-one analogs. First, routes toward the 4,5,6,7-tetrahydroindol-4-one starting materials are summarized, followed by synthetic pathways towards polyheterocyclic structures which are categorized based [...] Read more.
This review focuses on the synthesis of polyheterocyclic structures with a variety of medicinal and optoelectronic applications, starting from readily available 4,5,6,7-tetrahydroindol-4-one analogs. First, routes toward the 4,5,6,7-tetrahydroindol-4-one starting materials are summarized, followed by synthetic pathways towards polyheterocyclic structures which are categorized based on the size and attachment point of the newly formed (hetero)cyclic ring. Full article
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Article
3-Benzoylisoxazolines by 1,3-Dipolar Cycloaddition: Chloramine-T-Catalyzed Condensation of α-Nitroketones with Dipolarophiles
Molecules 2021, 26(12), 3491; https://doi.org/10.3390/molecules26123491 - 08 Jun 2021
Viewed by 653
Abstract
In this study, 3-benzoylisoxazolines were synthesized by reacting alkenes with various α-nitroketones using chloramine-T as the base. The scope of α-nitroketones and alkenes is extensive, including different alkenes and alkynes to form various isoxazolines and isoxazoles. The use of chloramine-T, as the low-cost, [...] Read more.
In this study, 3-benzoylisoxazolines were synthesized by reacting alkenes with various α-nitroketones using chloramine-T as the base. The scope of α-nitroketones and alkenes is extensive, including different alkenes and alkynes to form various isoxazolines and isoxazoles. The use of chloramine-T, as the low-cost, easily handled, moderate base for 1,3-dipolar cycloaddition is attractive. Full article
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Article
Synthesis and Rational Design of New Appended 1,2,3-Triazole-uracil Ensembles as Promising Anti-Tumor Agents via In Silico VEGFR-2 Transferase Inhibition
Molecules 2021, 26(7), 1952; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26071952 - 30 Mar 2021
Viewed by 548
Abstract
Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles 5ar were designed and synthesized via the click reaction. The ligands were well characterized [...] Read more.
Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles 5ar were designed and synthesized via the click reaction. The ligands were well characterized using 1H-, 13C-NMR, elemental analysis and ESI-mass spectrometry. The in silico binding propinquities of the ligands were studied sequentially in the active region of VEGFR-2 using the Molegro virtual docker. All the compounds produced remarkable interactions and potentially inhibitory ligands against VEGFR-2 were obtained with high negative binding energies. Drug-likeness was assessed from the ADME properties. Cytotoxicity of the test compounds was measured against HeLa and HUH-7 tumor cells and NIH/3T3 normal cells by MTT assay. Compound 5h showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC50 values of 4.5 and 7.7 μM respectively. Interestingly, the compounds 5ar did not show any cytotoxicity towards the normal cell lines. The results advance the position of substituted triazoles in the area of drug design with no ambiguity. Full article
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Article
Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates
Molecules 2021, 26(4), 890; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26040890 - 08 Feb 2021
Viewed by 649
Abstract
An efficient synthetic route to highly substituted dihydroquinolines and dihydronaphthyridines has been developed using a domino reaction of Morita-Baylis-Hillman (MBH) acetates with primary aliphatic and aromatic amines in DMF at 50–90 °C. The MBH substrates incorporate a side chain acetate positioned adjacent to [...] Read more.
An efficient synthetic route to highly substituted dihydroquinolines and dihydronaphthyridines has been developed using a domino reaction of Morita-Baylis-Hillman (MBH) acetates with primary aliphatic and aromatic amines in DMF at 50–90 °C. The MBH substrates incorporate a side chain acetate positioned adjacent to an acrylate or acrylonitrile aza-Michael acceptor as well as an aromatic ring activated toward SNAr ring closure. A control experiment established that the initial reaction was an SN2′-type displacement of the side chain acetate by the amine to generate the alkene product with the added nitrogen nucleophile positioned trans to the SNAr aromatic ring acceptor. Thus, equilibration of the initial alkene geometry is required prior to cyclization. A further double bond migration was observed for several reactions targeting dihydronaphthyridines from substrates with a side chain acrylonitrile moiety. MBH acetates incorporating a 2,5-difluorophenyl moiety were found to have dual reactivity in these annulations. In the absence of O2, the expected dihydroquinolines were formed, while in the presence of O2, quinolones were produced. All of the products were isolated in good to excellent yields (72–93%). Numerous cases (42) are reported, and mechanisms are discussed. Full article
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2020

Jump to: 2021, 2019, 2018, 2017, 2016, 2015

Article
A General and Scalable Synthesis of Polysubstituted Indoles
Molecules 2020, 25(23), 5595; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25235595 - 28 Nov 2020
Viewed by 707
Abstract
A consecutive 2-step synthesis of N-unprotected polysubstituted indoles bearing an electron-withdrawing group at the C-3 position from readily available nitroarenes is reported. The protocol is based on the [3,3]-sigmatropic rearrangement of N-oxyenamines generated by the DABCO-catalyzed reaction of N-arylhydroxylamines and [...] Read more.
A consecutive 2-step synthesis of N-unprotected polysubstituted indoles bearing an electron-withdrawing group at the C-3 position from readily available nitroarenes is reported. The protocol is based on the [3,3]-sigmatropic rearrangement of N-oxyenamines generated by the DABCO-catalyzed reaction of N-arylhydroxylamines and conjugated terminal alkynes, and delivers indoles endowed with a wide array of substitution patterns and topologies. Full article
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Review
Synthetic Strategies, Reactivity and Applications of 1,5-Naphthyridines
Molecules 2020, 25(14), 3252; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25143252 - 16 Jul 2020
Cited by 1 | Viewed by 1073
Abstract
This review covers the synthesis and reactivity of 1,5-naphthyridine derivatives published in the last 18 years. These heterocycles present a significant importance in the field of medicinal chemistry because many of them exhibit a great variety of biological activities. First, the published strategies [...] Read more.
This review covers the synthesis and reactivity of 1,5-naphthyridine derivatives published in the last 18 years. These heterocycles present a significant importance in the field of medicinal chemistry because many of them exhibit a great variety of biological activities. First, the published strategies related to the synthesis of 1,5-naphthyridines are presented followed by the reactivity of these compounds with electrophilic or nucleophilic reagents, in oxidations, reductions, cross-coupling reactions, modification of side chains or formation of metal complexes. Finally, some properties and applications of these heterocycles studied during this period are examined. Full article
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Communication
Two Annulated Azaheterocyclic Cores Readily Available from a Single Tetrahydroisoquinolonic Castagnoli–Cushman Precursor
Molecules 2020, 25(9), 2049; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25092049 - 28 Apr 2020
Viewed by 816
Abstract
A novel approach to indolo[3,2-c]isoquinoline and dibenzo[c,h][1,6]naphthyridine tetracyclic systems was discovered based on switchable reduction of 2-methoxy-3-(2-nitrophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid prepared via Castagnoli–Cushman reaction. Reduction with ammonium formate resulted in the expected selective transformation of the nitro group (thus [...] Read more.
A novel approach to indolo[3,2-c]isoquinoline and dibenzo[c,h][1,6]naphthyridine tetracyclic systems was discovered based on switchable reduction of 2-methoxy-3-(2-nitrophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid prepared via Castagnoli–Cushman reaction. Reduction with ammonium formate resulted in the expected selective transformation of the nitro group (thus providing access to substituted dibenzo[c,h][1,6]naphthyridine via cyclization and dehydrogenation). However, attempted reduction with sodium sulfide initiated a previously unknown reaction cascade including double reduction, cyclization, and decarboxylation, leading to formation of indolo[3,2-c]isoquinoline polyheterocycle in one synthetic step. Full article
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Article
Synthesis and Antibacterial Evaluation of Novel 1,3,4-Oxadiazole Derivatives Containing Sulfonate/Carboxylate Moiety
Molecules 2020, 25(7), 1488; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25071488 - 25 Mar 2020
Cited by 1 | Viewed by 1199
Abstract
In order to discover new lead compounds with high antibacterial activity, a series of new derivatives were designed and synthesized by introducing a sulfonate or carboxylate moiety into the 1,3,4-oxadiazole structure. Antibacterial activity against two phytopathogens, Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas [...] Read more.
In order to discover new lead compounds with high antibacterial activity, a series of new derivatives were designed and synthesized by introducing a sulfonate or carboxylate moiety into the 1,3,4-oxadiazole structure. Antibacterial activity against two phytopathogens, Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac), was assayed in vitro. The preliminary results indicated that ten compounds including 4a-1-4a-4 and 4a-11-4a-16 had good antibacterial activity against Xoo, with EC50 values ranging from 50.1-112.5 µM, which was better than those of Bismerthiazol (253.5 µM) and Thiodiazole copper (467.4 µM). Meanwhile, 4a-1, 4a-2, 4a-3 and 4a-4 demonstrated good inhibitory effect against Xanthomonas axonopodis pv. citri with EC50 values around 95.8-155.2 µM which were better than those of bismerthiazol (274.3 µM) and thiodiazole copper (406.3 µM). In addition, in vivo protection activity of compound 4a-2 and 4a-3 against rice bacterial leaf blight was 68.6% and 62.3%, respectively, which were better than bismerthiazol (49.6%) and thiodiazole copper (42.2%). Curative activity of compound 4a-2 and 4a-3 against rice bacterial leaf blight was 62.3% and 56.0%, which were better than bismerthiazol (42.9%) and thiodiazole copper (36.1%). Through scanning electron microscopy (SEM) analysis, it was observed that compound 4a-2 caused the cell membrane of Xanthomonas oryzae pv. oryzae ruptured or deformed. The present results indicated novel derivatives of 5-phenyl sulfonate methyl 1,3,4-oxadiazole might be potential antibacterial agents. Full article
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Article
Formal [3+2] Cycloaddition Reactions of Electron-Rich Aryl Epoxides with Alkenes under Lewis Acid Catalysis Affording Tetrasubstituted Tetrahydrofurans
Molecules 2020, 25(3), 692; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25030692 - 06 Feb 2020
Viewed by 1192
Abstract
We report on the regio- and stereoselective synthesis of tetrahydrofurans by reaction between epoxides and alkenes in the presence of a Lewis acid. This is an unprecedented formal [3+2] cycloaddition reaction between an epoxide and an alkene. The chemical reaction represents a very [...] Read more.
We report on the regio- and stereoselective synthesis of tetrahydrofurans by reaction between epoxides and alkenes in the presence of a Lewis acid. This is an unprecedented formal [3+2] cycloaddition reaction between an epoxide and an alkene. The chemical reaction represents a very concise synthesis of tetrahydrofurans from accessible starting compounds. Full article
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2019

Jump to: 2021, 2020, 2018, 2017, 2016, 2015

Article
A Suitable Functionalization of Nitroindazoles with Triazolyl and Pyrazolyl Moieties via Cycloaddition Reactions
Molecules 2020, 25(1), 126; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25010126 - 28 Dec 2019
Viewed by 1042
Abstract
The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)- and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N [...] Read more.
The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N-(2-bromoethyl)- and N-vinyl-nitro-1H-indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N-(2-bromoethyl)nitroindazoles into the corresponding azide. The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields. Full article
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Article
Synthesis and Antimicrobial Activity of a New Series of Thiazolidine-2,4-diones Carboxamide and Amino Acid Derivatives
Molecules 2020, 25(1), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25010105 - 27 Dec 2019
Cited by 5 | Viewed by 1241
Abstract
Novel thiazolidine-2,4-dione carboxamide and amino acid derivatives were synthesized in excellent yield using OxymaPure/N,N′-diisopropylcarbodimide coupling methodology and were characterized by chromatographic and spectrometric methods, and elemental analysis. The antimicrobial and antifungal activity of these derivatives was evaluated against two Gram-positive bacteria [...] Read more.
Novel thiazolidine-2,4-dione carboxamide and amino acid derivatives were synthesized in excellent yield using OxymaPure/N,N′-diisopropylcarbodimide coupling methodology and were characterized by chromatographic and spectrometric methods, and elemental analysis. The antimicrobial and antifungal activity of these derivatives was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), two-Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and one fungal isolate (Candida albicans). Interestingly, several samples demonstrated weak to moderate antibacterial activity against Gram-negative bacteria, as well as antifungal activity. However, only one compound namely, 2-(5-(3-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid, showed antibacterial activity against Gram-positive bacteria, particularly S. aureus. Full article
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Article
Synthesis and Antimicrobial Activity of Some New Substituted Quinoxalines
Molecules 2019, 24(22), 4198; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24224198 - 19 Nov 2019
Cited by 9 | Viewed by 1200
Abstract
A number of new symmetrically and asymmetrically 2,3-disubstituted quinoxalines were synthesized through functionalization of 2,3-dichloroquinoxaline (2,3-DCQ) with a variety of sulfur and/or nitrogen nucleophiles. The structures of the obtained compounds were established based on their spectral data and elemental analysis. The antimicrobial activity [...] Read more.
A number of new symmetrically and asymmetrically 2,3-disubstituted quinoxalines were synthesized through functionalization of 2,3-dichloroquinoxaline (2,3-DCQ) with a variety of sulfur and/or nitrogen nucleophiles. The structures of the obtained compounds were established based on their spectral data and elemental analysis. The antimicrobial activity for the prepared compounds was investigated against four bacterial species and two fungal strains. The symmetrically disubstituted quinoxalines 2, 3, 4, and 5 displayed the most significant antibacterial activity, while compounds 6a, 6b, and the pentacyclic compound 10 showed considerable antifungal activity. Furthermore, compounds 3f, 6b showed broad antimicrobial spectrum against most of the tested strains. Full article
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Review
Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications
Molecules 2019, 24(22), 4161; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24224161 - 16 Nov 2019
Cited by 5 | Viewed by 1669
Abstract
Pyrido[2,3-d]pyrimidines (1) are a type of privileged heterocyclic scaffolds capable of providing ligands for several receptors in the body. Among such structures, our group and others have been particularly interested in pyrido[2,3-d]pyrimidine-7(8H)-ones (2) [...] Read more.
Pyrido[2,3-d]pyrimidines (1) are a type of privileged heterocyclic scaffolds capable of providing ligands for several receptors in the body. Among such structures, our group and others have been particularly interested in pyrido[2,3-d]pyrimidine-7(8H)-ones (2) due to the similitude with nitrogen bases present in DNA and RNA. Currently there are more than 20,000 structures 2 described which correspond to around 2900 references (half of them being patents). Furthermore, the number of references containing compounds of general structure 2 have increased almost exponentially in the last 10 years. The present review covers the synthetic methods used for the synthesis of pyrido[2,3-d]pyrimidine-7(8H)-ones (2), both starting from a preformed pyrimidine ring or a pyridine ring, and the biomedical applications of such compounds. Full article
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Article
A Simple, Efficient, and Eco-Friendly Method for the Preparation of 3-Substituted-2,3-dihydroquinazolin-4(1H)-one Derivatives
Molecules 2019, 24(22), 4052; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24224052 - 09 Nov 2019
Cited by 1 | Viewed by 922
Abstract
A simple, cost-effective method under environmentally benign conditions is a very important concept for the preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives. The present work describes an efficient and eco-friendly protocol for the synthesis of 2-amino-N-(2-substituted-ethyl)benzamide and 3-substituted-2,3-dihydroquinazolin-4(1H)-one derivatives. The [...] Read more.
A simple, cost-effective method under environmentally benign conditions is a very important concept for the preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives. The present work describes an efficient and eco-friendly protocol for the synthesis of 2-amino-N-(2-substituted-ethyl)benzamide and 3-substituted-2,3-dihydroquinazolin-4(1H)-one derivatives. The novel feature of this protocol is the use of 2-methyl tetrahydrofuran (2-MeTHF) as an eco-friendly alternative solvent to tetrahydrofuran (THF) in the first step. In the second step, methanol in the presence of potassium carbonate as a catalyst was used under conventional heating or microwave irradiation, which provided an eco-friendly method to afford the target products in excellent yields and purities. NMR (1H and 13C), elemental analysis, and LC-MS confirmed the structures of all compounds. X-ray crystallography further confirmed the structure of the intermediate 2-amino-N-(2-substituted-ethyl)benzamide 3a. The molecular structure of 3a was monoclinic crystal, with P21/c, a = 13.6879 (11) Å, b = 10.2118 (9) Å, c = 9.7884 (9) Å, β = 105.068 (7)°, V = 1321.2 (2) Å3, and Z = 4. Full article
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Article
One Pot and Metal-Free Approach to 3-(2-Hydroxybenzoyl)-1-aza-anthraquinones
Molecules 2019, 24(16), 3017; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24163017 - 20 Aug 2019
Cited by 1 | Viewed by 1110
Abstract
Herein, a direct strategy to synthesize 3-(2-hydroxybenzoyl)-1-aza-anthraquinones with excellent efficiency, mild conditions, and benign functional group compatibility was reported. A variety of 3-formylchromone compounds were employed as compatible substrates and this protocol gave the 3-(2-hydroxybenzoyl)-1-aza-anthraquinone derivatives in good to excellent yields without inert [...] Read more.
Herein, a direct strategy to synthesize 3-(2-hydroxybenzoyl)-1-aza-anthraquinones with excellent efficiency, mild conditions, and benign functional group compatibility was reported. A variety of 3-formylchromone compounds were employed as compatible substrates and this protocol gave the 3-(2-hydroxybenzoyl)-1-aza-anthraquinone derivatives in good to excellent yields without inert gas and expensive transition metal catalysts. Some compounds displayed good anti-proliferative activities. Full article
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Article
Intramolecular Carbene C-H Insertion Reactions of 2-Diazo-2-sulfamoylacetamides
Molecules 2019, 24(14), 2628; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24142628 - 19 Jul 2019
Viewed by 1214
Abstract
The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo- [...] Read more.
The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo-N,N-dimethyl-2-(N,N-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its N-phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[c]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(N,N-dialkylsulfamoyl)acetamides; and (3) for 2-diazo-N-phenyl-2-(N-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the N-phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the N-aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group. Full article
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Article
Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights
Molecules 2019, 24(12), 2328; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24122328 - 25 Jun 2019
Cited by 2 | Viewed by 1657
Abstract
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of [...] Read more.
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N’-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated β-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson’s. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it. Full article
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Article
Facile Assembling of Novel 2,3,6,7,9-pentaazabicyclo- [3.3.1]nona-3,7-diene Derivatives under Microwave and Ultrasound Platforms
Molecules 2019, 24(6), 1110; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24061110 - 20 Mar 2019
Cited by 2 | Viewed by 1072
Abstract
Reactions of a series of 3-oxo-2-arylhydrazonopropanal derivatives with two molar ratio of ammonium acetate afforded a library of tetrasubstituted 2,3,6,7,9-pentaazabicyclo[3.3.1]nona- 3,7-diene derivatives in good to excellent isolated yields. The reaction was activated with triethylamine catalyst under three different heating modes: thermal, ultrasonic and [...] Read more.
Reactions of a series of 3-oxo-2-arylhydrazonopropanal derivatives with two molar ratio of ammonium acetate afforded a library of tetrasubstituted 2,3,6,7,9-pentaazabicyclo[3.3.1]nona- 3,7-diene derivatives in good to excellent isolated yields. The reaction was activated with triethylamine catalyst under three different heating modes: thermal, ultrasonic and microwave irradiating conditions in ethanol solvent. The structures of the isolated products were fully characterized by spectral and analytical data as well as X-ray single crystal of selected examples. Full article
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Article
Synthesis, In Vitro Antimicrobial and Cytotoxic Activities of Some New Pyrazolo[1,5-a]pyrimidine Derivatives
Molecules 2019, 24(6), 1080; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24061080 - 19 Mar 2019
Cited by 11 | Viewed by 1502
Abstract
A new series of pyrazole 47 and pyrazolo[1,5-a]pyrimidine 813 were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and antitumor activities. Symmetrical and asymmetrical 3,6-diarylazo-2,5,7-triaminopyrazolo[1,5-a]pyrimidine were synthesized by the conventional [...] Read more.
A new series of pyrazole 47 and pyrazolo[1,5-a]pyrimidine 813 were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and antitumor activities. Symmetrical and asymmetrical 3,6-diarylazo-2,5,7-triaminopyrazolo[1,5-a]pyrimidine were synthesized by the conventional method and also subjected to microwave irradiation and under ultrasound conditions. The biological results revealed that most of the tested compounds proved to be active as antibacterial and antifungal agents. The antitumor activity of the synthesized compounds was evaluated against human cancer cell lines, MCF-7, HCT-116, and HepG-2, as compared with Doxorubicin as a control. Full article
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Article
Convenient Synthesis of 6,7,12,13-Tetrahydro-5H-Cyclohepta[2,1-b:3,4-b’]diindole Derivatives Mediated by Hypervalent Iodine (III) Reagent
Molecules 2019, 24(5), 960; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24050960 - 08 Mar 2019
Cited by 5 | Viewed by 1260
Abstract
Bisindolyl alkaloids represent a large family of natural and synthetic products that display various biological activities. Among the bisindole compounds, 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindoles have received little attention. Only two methods have been developed for the construction of the 6,7,12,13-tetrahydro-5 [...] Read more.
Bisindolyl alkaloids represent a large family of natural and synthetic products that display various biological activities. Among the bisindole compounds, 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindoles have received little attention. Only two methods have been developed for the construction of the 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindole scaffold thus far, including the classical Fischer indole synthesis conducted by reacting indole-fused cycloheptanone and hydrazines, and the condensation reaction to build the seven-membered ring. Here, we report for the first time a new route to synthesize 6,7,12,13-tetrahydro-5H-cyclohepta[2,1-b:3,4-b’]diindoles through intramolecular oxidative coupling of 1,3-di(1H-indol-3-yl)propanes in the presence of PIFA, DDQ and TMSCl with moderate to excellent yields. Full article
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Article
Facile Access to Fe(III)-Complexing Cyclic Hydroxamic Acids in a Three-Component Format
Molecules 2019, 24(5), 864; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24050864 - 28 Feb 2019
Cited by 4 | Viewed by 1246
Abstract
Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic [...] Read more.
Cyclic hydroxamic acids can be viewed as effective binders of soluble iron and can therefore be useful moieties for employing in compounds to treat iron overload disease. Alternatively, they are analogs of bacterial siderophores (iron-scavenging metabolites) and can find utility in designing antibiotic constructs for targeted delivery. An earlier described three-component variant of the Castagnoli—Cushman reaction of homophthalic acid (via in situ cyclodehydration to the respective anhydride) was extended to involve hydroxylamine in lieu of the amine component of the reaction. Using hydroxylamine acetate and O-benzylhydroxylamine was key to the success of this transformation due to greater solubility of the reagents in refluxing toluene (compared to hydrochloride salt). The developed protocol was found suitable for multigram-scale syntheses of N-hydroxy- and N-(benzyloxy)tetrahydroisoquinolonic acids. The cyclic hydroxamic acids synthesized in the newly developed format have been tested and shown to be efficient ligands for Fe3+, which makes them suitable candidates for the above-mentioned applications. Full article
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Article
Synthesis of 4-Alkyl-4H-1,2,4-triazole Derivatives by Suzuki Cross-Coupling Reactions and Their Luminescence Properties
Molecules 2019, 24(3), 652; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24030652 - 12 Feb 2019
Cited by 3 | Viewed by 1714
Abstract
New derivatives of 4-alkyl-3,5-diaryl-4H-1,2,4-triazole were synthesized utilizing the Suzuki cross-coupling reaction. The presented methodology comprises of the preparation of bromine-containing 4-alkyl-4H-1,2,4-triazoles and their coupling with different commercially available boronic acids in the presence of ionic liquids or in conventional [...] Read more.
New derivatives of 4-alkyl-3,5-diaryl-4H-1,2,4-triazole were synthesized utilizing the Suzuki cross-coupling reaction. The presented methodology comprises of the preparation of bromine-containing 4-alkyl-4H-1,2,4-triazoles and their coupling with different commercially available boronic acids in the presence of ionic liquids or in conventional solvents. The obtained compounds were tested for their luminescence properties. Full article
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2018

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Article
HFIP-Promoted Bischler Indole Synthesis under Microwave Irradiation
Molecules 2018, 23(12), 3317; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23123317 - 14 Dec 2018
Cited by 1 | Viewed by 1521
Abstract
1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was found to be effective for the Bischler indole synthesis under microwave irradiation in the absence of a metal catalyst. Under the catalysis of HFIP, a wide range of α-amino arylacetones were successfully transformed into indole derivatives with moderate to good [...] Read more.
1,1,1,3,3,3-Hexafluoropropan-2-ol (HFIP) was found to be effective for the Bischler indole synthesis under microwave irradiation in the absence of a metal catalyst. Under the catalysis of HFIP, a wide range of α-amino arylacetones were successfully transformed into indole derivatives with moderate to good yields. Full article
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Article
Synthesis, Antibacterial, and Anti HepG2 Cell Line Human Hepatocyte Carcinoma Activity of Some New Potentially Benzimidazole-5-(Aryldiazenyl)Thiazole Derivatives
Molecules 2018, 23(12), 3285; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23123285 - 11 Dec 2018
Cited by 9 | Viewed by 1584
Abstract
The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence [...] Read more.
The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence underwent interesting functionalization reactions to afford several series of benzimidazole-5-(aryldiazenyl)thiazole derivatives: 3ac, 7ac, and 8ac. The antibacterial activities of the synthesized compounds were evaluated by calculation of the inhibition zone diameter (mm) and the determination of minimum inhibitory concentration (µg/mL) against selected pathogenic bacteria Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria).Noticeable efficiency was found based on in vitro screening for their antioxidant activity and cytotoxicity effect against the human liver cancer cell line (HepG2) and human hepatocyte carcinoma cells at relatively high concentrations. Full article
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Article
Conversion of Medium-Sized Lactams to α-Vinyl or α-Acetylenyl Azacycles via N,O-Acetal TMS Ethers
Molecules 2018, 23(11), 3023; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23113023 - 19 Nov 2018
Cited by 5 | Viewed by 1606
Abstract
α-Vinyl or α-acetylenyl azacycles were easily synthesized from 7- to 9-membered lactams and 6- to 9-membered lactams via N,O-acetal trimethylsilyl (TMS) ethers. Organocopper and organostannane reagents afforded reasonable yields for the respective N-acyliminium ion vinylation and acetylenylation intermediates generated [...] Read more.
α-Vinyl or α-acetylenyl azacycles were easily synthesized from 7- to 9-membered lactams and 6- to 9-membered lactams via N,O-acetal trimethylsilyl (TMS) ethers. Organocopper and organostannane reagents afforded reasonable yields for the respective N-acyliminium ion vinylation and acetylenylation intermediates generated from N,O-acetal TMS ethers in the presence of a Lewis acid. Full article
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Article
Eco-Friendly Synthesis, Characterization and Biological Evaluation of Some Novel Pyrazolines Containing Thiazole Moiety as Potential Anticancer and Antimicrobial Agents
Molecules 2018, 23(11), 2970; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23112970 - 14 Nov 2018
Cited by 18 | Viewed by 1521
Abstract
The one-pot synthesis of a series of pyrazoline derivatives containing the bioactive thiazole ring has been performed through a 1,3-dipolar cycloaddition reaction of N-thiocarbamoylpyrazoline and different hydrazonoyl halides or α-haloketones in the presence of DABCO (1,4-diazabicyclo[2.2.2] octane) as an eco-friendly catalyst using [...] Read more.
The one-pot synthesis of a series of pyrazoline derivatives containing the bioactive thiazole ring has been performed through a 1,3-dipolar cycloaddition reaction of N-thiocarbamoylpyrazoline and different hydrazonoyl halides or α-haloketones in the presence of DABCO (1,4-diazabicyclo[2.2.2] octane) as an eco-friendly catalyst using the solvent-drop grinding method. The structure of the synthesized compounds was elucidated using elemental and spectroscopic analyses (IR, NMR, and Mass). The activity of these compounds against human hepatocellular carcinoma cell line (HepG2) was tested and the results showed that the pyrazoline 11f, which has a fluorine substituent, is the most active. The antimicrobial activities of the newly synthesized compounds were determined against two fungi and four bacterial strains, and the results indicated that some of the newly synthesized pyrazolines are more potent than the standard drugs against test organisms. Full article
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Article
From Quinoxaline, Pyrido[2,3-b]pyrazine and Pyrido[3,4-b]pyrazine to Pyrazino-Fused Carbazoles and Carbolines
Molecules 2018, 23(11), 2961; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23112961 - 13 Nov 2018
Cited by 4 | Viewed by 2353
Abstract
2,3-Diphenylated quinoxaline, pyrido[2,3-b]pyrazine and 8-bromopyrido[3,4-b]pyrazine were halogenated in deprotometalation-trapping reactions using mixed 2,2,6,6-tetramethyl piperidino-based lithium-zinc combinations in tetrahydrofuran. The 2,3-diphenylated 5-iodo- quinoxaline, 8-iodopyrido[2,3-b]pyrazine and 8-bromo-7-iodopyrido[3,4-b]pyrazine thus obtained were subjected to palladium-catalyzed couplings with arylboronic acids [...] Read more.
2,3-Diphenylated quinoxaline, pyrido[2,3-b]pyrazine and 8-bromopyrido[3,4-b]pyrazine were halogenated in deprotometalation-trapping reactions using mixed 2,2,6,6-tetramethyl piperidino-based lithium-zinc combinations in tetrahydrofuran. The 2,3-diphenylated 5-iodo- quinoxaline, 8-iodopyrido[2,3-b]pyrazine and 8-bromo-7-iodopyrido[3,4-b]pyrazine thus obtained were subjected to palladium-catalyzed couplings with arylboronic acids or anilines, and possible subsequent cyclizations to afford the corresponding pyrazino[2,3-a]carbazole, pyrazino[2′,3′:5,6] pyrido[4,3-b]indole and pyrazino[2′,3′:4,5]pyrido[2,3-d]indole, respectively. 8-Iodopyrido[2,3-b] pyrazine was subjected either to a copper-catalyzed C-N bond formation with azoles, or to direct substitution to introduce alkylamino, benzylamino, hydrazine and aryloxy groups at the 8 position. The 8-hydrazino product was converted into aryl hydrazones. Most of the compounds were evaluated for their biological properties (antiproliferative activity in A2058 melanoma cells and disease-relevant kinase inhibition). Full article
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Article
Quinazolin-4(3H)-ones and 5,6-Dihydropyrimidin-4(3H)-ones from β-Aminoamides and Orthoesters
Molecules 2018, 23(11), 2925; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23112925 - 09 Nov 2018
Cited by 7 | Viewed by 1506
Abstract
Quinazolin-4(3H)-ones have been prepared in one step from 2-aminobenzamides and orthoesters in the presence of acetic acid. Simple 2-aminobenzamides were easily converted to the heterocycles by refluxing in absolute ethanol with 1.5 equivalents of the orthoester and 2 equivalents of acetic [...] Read more.
Quinazolin-4(3H)-ones have been prepared in one step from 2-aminobenzamides and orthoesters in the presence of acetic acid. Simple 2-aminobenzamides were easily converted to the heterocycles by refluxing in absolute ethanol with 1.5 equivalents of the orthoester and 2 equivalents of acetic acid for 12–24 h. Ring-substituted and hindered 2-aminobenzamides as well as cases incorporating an additional basic nitrogen required pressure tube conditions with 3 equivalents each of the orthoester and acetic acid in ethanol at 110 °C for 12–72 h. The reaction was tolerant towards functionality on the benzamide and a range of structures was accessible. Workup involved removal of the solvent under vacuum and either recrystallization from ethanol or trituration with ether-pentane. Several 5,6-dihydropyrimidin-4(3H)-ones were also prepared from 3-amino-2,2-dimethylpropionamide. All products were characterized by melting point, FT-IR, 1H-NMR, 13C-NMR, and HRMS. Full article
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Article
Regioselective Synthesis of New 2,4-(Het)aryl-3H-pyrido[1′,2′:1,5]pyrazolo[4,3-d]pyrimidines Involving Palladium-Catalyzed Cross-Coupling Reactions
Molecules 2018, 23(11), 2740; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23112740 - 23 Oct 2018
Cited by 2 | Viewed by 1306
Abstract
The design of some novel di-(het)arylated-3H-pyrido[1′,2′:1,5]pyrazolo[4,3-d]pyrimidine derivatives is reported. The series was developed from 1-aminopyridinium iodide, which afforded the key intermediate bearing two thiomethyl and amide functions, each of them useful for palladium catalyzed cross coupling reactions by alkyl [...] Read more.
The design of some novel di-(het)arylated-3H-pyrido[1′,2′:1,5]pyrazolo[4,3-d]pyrimidine derivatives is reported. The series was developed from 1-aminopyridinium iodide, which afforded the key intermediate bearing two thiomethyl and amide functions, each of them useful for palladium catalyzed cross coupling reactions by alkyl sulfur release and C-O activation, respectively. The two regioselective and successive cross-coupling reactions were first carried out in C-4 by in situ C-O activation and next in C-2 by a methylsulfur release. Process optimization furnished conditions leading to products in high yields. The scope and limitations of the methodologies were evaluated and the final compounds characterized. Full article
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Review
Synthesis of Multi-Substituted Pyrrole Derivatives Through [3+2] Cycloaddition with Tosylmethyl Isocyanides (TosMICs) and Electron-Deficient Compounds
Molecules 2018, 23(10), 2666; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23102666 - 17 Oct 2018
Cited by 20 | Viewed by 2744
Abstract
Pyrrole and its polysubstituted derivatives are important five-membered heterocyclic compounds, which exist alone or as a core framework in many pharmaceutical and natural product structures, some of which have good biological activities. The Van Leusen [3+2] cycloaddition reaction based on tosylmethyl isocyanides (TosMICs) [...] Read more.
Pyrrole and its polysubstituted derivatives are important five-membered heterocyclic compounds, which exist alone or as a core framework in many pharmaceutical and natural product structures, some of which have good biological activities. The Van Leusen [3+2] cycloaddition reaction based on tosylmethyl isocyanides (TosMICs) and electron-deficient compounds as a substrate, which has been continuously developed due to its advantages such as operationally simple, easily available starting materials, and broadly range of substrates, is one of the most convenient methods to synthetize pyrrole heterocycles. In this review, we discuss the different types of two carbon synthons in the Van Leusen pyrrole reaction and give a summary of the progress of these synthesis methods in the past two decades. Full article
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Article
Synthesis, Spectroscopic Characterization, and In Vitro Antibacterial Evaluation of Novel Functionalized Sulfamidocarbonyloxyphosphonates
Molecules 2018, 23(7), 1682; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23071682 - 10 Jul 2018
Cited by 3 | Viewed by 1804
Abstract
Several new sulfamidocarbonyloxyphosphonates were prepared in two steps, namely carbamoylation and sulfamoylation, by using chlorosulfonyl isocyanate (CSI), α-hydroxyphosphonates, and various amino derivatives and related (primary or secondary amines, β-amino esters, and oxazolidin-2-ones). All structures were confirmed by 1H, 13C, and 31 [...] Read more.
Several new sulfamidocarbonyloxyphosphonates were prepared in two steps, namely carbamoylation and sulfamoylation, by using chlorosulfonyl isocyanate (CSI), α-hydroxyphosphonates, and various amino derivatives and related (primary or secondary amines, β-amino esters, and oxazolidin-2-ones). All structures were confirmed by 1H, 13C, and 31P NMR spectroscopy, IR spectroscopy, and mass spectroscopy, as well as elemental analysis. Eight compounds were evaluated for their in vitro antibacterial activity against four reference bacteria including Gram-positive Staphylococcus aureus (ATCC 25923), and Gram-negative Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Pseudomonas aeruginosa (ATCC 27853), in addition to three clinical strains of each studied bacterial species. Compounds 1a7a and 1b showed significant antibacterial activity compared to sulfamethoxazole/trimethoprim, the reference drug used in this study. Full article
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Correction
Correction: El-kalyoubi, S.; et al. Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and Antimicrobial Activity. Molecules, 2015, 20, 19263–19276
Molecules 2018, 23(7), 1592; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23071592 - 29 Jun 2018
Viewed by 1466
Abstract
The authors wish to make the following changes to their paper [1].[...] Full article
Article
Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
Molecules 2018, 23(6), 1280; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23061280 - 26 May 2018
Cited by 3 | Viewed by 1647
Abstract
A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On [...] Read more.
A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine–amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On the other hand, reduction and alkylation reactions of 8-fluoro-3,4-dihydroisoquinoline led to novel 1,2,3,4-tetrahydroisoquinoline derivatives that can be used as building blocks in the synthesis of potential central nervous system drug candidates. Full article
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Article
Synthesis and Pharmacological Studies of Unprecedented Fused Pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine Derivatives
Molecules 2018, 23(5), 1024; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23051024 - 27 Apr 2018
Cited by 4 | Viewed by 1867
Abstract
A novel fused system with three or four fused rings—pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the [...] Read more.
A novel fused system with three or four fused rings—pyridazino[3′,4′:5,6][1,2,4]triazino[4,3-b][1,2,4,5]tetrazine and pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b]pyrimido[4,5-e][1,3,4]thiadiazine was obtained from the starting materials 4(6H)-amino-3-hydrazino-7-(2-thienyl)pyridazino[3,4-e][1,2,4]-triazine 2 and 9-amino-3-(2-thienyl)-2H,8H-pyridazino[3′,4′:5,6][1,2,4]triazino[3,4-b][1,3,4]thiadiazine-8-carbonitrile 12. Each of the starting compounds was subjected to a number of cyclization reactions to obtain a series of new heterocyclic fused systems, 310 and 1323, via bifunctional reagents. Some of the synthesized compounds were screened against three cell lines including HepG2, HCT-116 and MCF-7 to discover their anticancer activity. The synthesized compounds were characterized depending on their elemental analyses and spectral data. Full article
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Article
Synthesis of Some Novel Fused Pyrimido[4″,5″:5′,6′]-[1,2,4]triazino[3′,4′:3,4] [1,2,4]triazino[5,6-b]indoles with Expected Anticancer Activity
Molecules 2018, 23(3), 693; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23030693 - 19 Mar 2018
Cited by 8 | Viewed by 1984
Abstract
Our current goal is the synthesis of polyheterocyclic compounds starting from 3-amino-[1,2,4]triazino[5,6-b]indole 1 and studying their anticancer activity to determine whether increasing of the size of the molecules increases the anticancer activity or not. 1-Amino[1,2,4]triazino[3′,4′:3,4]-[1,2,4]triazino[5,6-b]indole-2-carbonitrile (4) was [...] Read more.
Our current goal is the synthesis of polyheterocyclic compounds starting from 3-amino-[1,2,4]triazino[5,6-b]indole 1 and studying their anticancer activity to determine whether increasing of the size of the molecules increases the anticancer activity or not. 1-Amino[1,2,4]triazino[3′,4′:3,4]-[1,2,4]triazino[5,6-b]indole-2-carbonitrile (4) was prepared by the diazotization of 3-amino[1,2,4]-triazino[5,6-b]indole 1 followed by coupling with malononitrile in basic medium then cyclization under reflux to get 4. Also, new fused pyrimido[4″,5″:5′,6′][1,2,4]triazino-[3′,4′:3,4][1,2,4]triazino[5,6-b]indole derivative 6 was prepared and used to obtain polycyclic heterocyclic systems. Confirmation of the synthesized compounds’ structures was carried out using elemental analyses and spectral data (IR, 1H-NMR and 13C-NMR and mass spectra). The anticancer activity of some of the synthesized compounds was tested against HepG2, HCT-116 and MCF-7 cell lines. The anticancer screening results showed that some derivatives display good activity which was more potent than that of the reference drug used. Molecular docking was used to predict the binding between some of the synthesized compounds and the prostate cancer 2q7k hormone and breast ‎cancer 3hb5 receptors. Full article
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Article
Syntheses of 1-Aryl-5-nitro-1H-indazoles and a General One-Pot Route to 1-Aryl-1H-indazoles
Molecules 2018, 23(3), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23030674 - 16 Mar 2018
Cited by 2 | Viewed by 2410
Abstract
An efficient route to substituted 1-aryl-1H-indazoles has been developed and optimized. The method involved the preparation of arylhydrazones from acetophenone or benzaldehyde substituted by fluorine at C2 and nitro at C5, followed by deprotonation and nucleophilic aromatic substitution (SNAr) [...] Read more.
An efficient route to substituted 1-aryl-1H-indazoles has been developed and optimized. The method involved the preparation of arylhydrazones from acetophenone or benzaldehyde substituted by fluorine at C2 and nitro at C5, followed by deprotonation and nucleophilic aromatic substitution (SNAr) ring closure in 45–90%. Modification of this procedure to a one-pot domino process was successful in the acetophenone series (73–96%), while the benzaldehyde series (63–73%) required a step-wise addition of reagents. A general one-pot protocol for 1-aryl-1H-indazole formation without the limiting substitution patterns required for the SNAr cyclization has also been achieved in 62–78% yields. A selection of 1-aryl-1H-indazoles was prepared in high yield by a procedure that requires only a single laboratory operation. Full article
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Article
Synthesis of Dihydrooxepino[3,2-c]Pyrazoles via Claisen Rearrangement and Ring-Closing Metathesis from 4-Allyloxy-1H-pyrazoles
Molecules 2018, 23(3), 592; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23030592 - 06 Mar 2018
Cited by 6 | Viewed by 1654
Abstract
Synthesis of novel pyrazole-fused heterocycles, i.e., dihydro-1H- or 2H-oxepino[3,2-c]pyrazoles (6 or 7) from 4-allyloxy-1H-pyrazoles (1) via combination of Claisen rearrangement and ring-closing metathesis (RCM) has been achieved. A suitable catalyst for [...] Read more.
Synthesis of novel pyrazole-fused heterocycles, i.e., dihydro-1H- or 2H-oxepino[3,2-c]pyrazoles (6 or 7) from 4-allyloxy-1H-pyrazoles (1) via combination of Claisen rearrangement and ring-closing metathesis (RCM) has been achieved. A suitable catalyst for the RCM of 5-allyl-4-allyloxy-1H-pyrazoles (4) was proved to be the Grubbs second generation catalyst (Grubbs2nd) to give the predicted RCM product at room temperature in three hours. The same reactions of the regioisomer, 3-allyl-4-allyloxy-1H-pyrazoles (5), also proceeded to give the corresponding RCM products. On the other hand, microwave aided RCM at 140 °C on both of 4 and 5 afforded mixtures of isomeric products with double bond rearrangement from normal RCM products in spite of remarkable reduction of the reaction time to 10 min. Full article
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Article
Synthesis and Optical Properties of Near-Infrared meso-Phenyl-Substituted Symmetric Heptamethine Cyanine Dyes
Molecules 2018, 23(2), 226; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23020226 - 24 Jan 2018
Cited by 14 | Viewed by 3037
Abstract
Heptamethine cyanine dyes are a class of near infrared fluorescence (NIRF) probes of great interest in bioanalytical and imaging applications due to their modifiability, allowing them to be tailored for particular applications. Generally, modifications at the meso-position of these dyes are achieved [...] Read more.
Heptamethine cyanine dyes are a class of near infrared fluorescence (NIRF) probes of great interest in bioanalytical and imaging applications due to their modifiability, allowing them to be tailored for particular applications. Generally, modifications at the meso-position of these dyes are achieved through Suzuki-Miyaura C-C coupling and SRN1 nucleophilic substitution of the chlorine atom at the meso-position of the dye. Herein, a series of 15 meso phenyl-substituted heptamethine cyanines was synthesized utilizing a modified dianil linker. Their optical properties, including molar absorptivity, fluorescence, Stokes shift, and quantum yield were measured. The HSA binding affinities of two representative compounds were measured and compared to that of a series of trimethine cyanines previously synthesized by our lab. The results indicate that the binding of these compounds to HSA is not only dependent on hydrophobicity, but may also be dependent on steric interferences in the binding site and structural dynamics of the NIRF compounds. Full article
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Article
Regioselectivity in Reactions between Bis(2-benzothiazolyl)ketone and Vinyl Grignard Reagents: C- versus O-alkylation—Part III
Molecules 2018, 23(1), 171; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23010171 - 15 Jan 2018
Cited by 2 | Viewed by 2051
Abstract
The reaction between bis(2-benzothiazolyl)ketone and vinyl Grignard reagents bearing different substituents on the vinyl moiety gave the product derived from attack on the carbonylic carbon- and/or oxygen-atom. The regioselectivity of the attack depends on the kind of substituents bound to the vinylic carbon [...] Read more.
The reaction between bis(2-benzothiazolyl)ketone and vinyl Grignard reagents bearing different substituents on the vinyl moiety gave the product derived from attack on the carbonylic carbon- and/or oxygen-atom. The regioselectivity of the attack depends on the kind of substituents bound to the vinylic carbon atoms and on their relative position. The reaction between vinylmagnesium bromide and 2-methyl-1-propenylmagnesium bromide was carried out under different experimental conditions and in the presence of radical scavengers. The results indicate a plausible mechanistic pathway involving radical intermediates in the case of O-alkylation, but a polar ones in the case of classic C-alkylation. This agrees with our previous reports indicating a key role played by the delocalization ability of the substituents bound to the carbonyl group in driving the regioselectivity of the vinylmagnesium bromide attack towards O-alkylation. Further support of this was obtained by diffractometric analysis of four distinct bis(heteroaryl)ketones. Full article
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2017

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Article
Energetic Di- and Trinitromethylpyridines: Synthesis and Characterization
Molecules 2018, 23(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23010002 - 21 Dec 2017
Cited by 3 | Viewed by 2409
Abstract
Pyridine derivatives based on the addition of trinitromethyl functional groups were synthesized by the reaction of N2O4 with the corresponding pyridinecarboxaldoximes, then they were converted into dinitromethylide hydrazinium salts. These energetic compounds were fully characterized by IR and NMR spectroscopy, [...] Read more.
Pyridine derivatives based on the addition of trinitromethyl functional groups were synthesized by the reaction of N2O4 with the corresponding pyridinecarboxaldoximes, then they were converted into dinitromethylide hydrazinium salts. These energetic compounds were fully characterized by IR and NMR spectroscopy, elemental analysis, differential scanning calorimetry (DSC), and X-ray crystallography. These pyridine derivatives have good densities, positive enthalpies of formation, and acceptable sensitivity values. Theoretical calculations carried out using Gaussian 03 and EXPLO5 programs demonstrated good to excellent detonation velocities and pressures. Each of these compounds is superior in performance to TNT, while 2,6-bis(trinitromethyl)pyridine (D = 8700 m·s−1, P = 33.2 GPa) shows comparable detonation performance to that of RDX, but its thermal stability is too low, making it inferior to RDX. Full article
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Article
Nucleobase–Guanidiniocarbonyl-Pyrrole Conjugates as Novel Fluorimetric Sensors for Single Stranded RNA
Molecules 2017, 22(12), 2213; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22122213 - 13 Dec 2017
Cited by 6 | Viewed by 2517
Abstract
We demonstrate here for the first time that a guanidiniocarbonyl-pyrrole (GCP) unit can be applied for the fine recognition of single stranded RNA sequences—an intuitively unexpected result since so far binding of the GCP unit to ds-DNA or ds-RNA relied strongly on minor [...] Read more.
We demonstrate here for the first time that a guanidiniocarbonyl-pyrrole (GCP) unit can be applied for the fine recognition of single stranded RNA sequences—an intuitively unexpected result since so far binding of the GCP unit to ds-DNA or ds-RNA relied strongly on minor or major groove interactions, as shown in previous work. Two novel nucleobase–GCP isosteric conjugates differing in the flexibility of GCP unit revealed a fluorimetric recognition of various single stranded RNA, which could be additionally regulated by pH. The more rigid conjugate showed a specific fluorescence increase for poly A only at pH 7, whereby this response could be reversibly switched-off at pH 5. The more flexible derivative revealed selective fluorescence quenching by poly G at pH 7 but no change for poly A, whereas its recognition of poly AH+ can be switched-on at pH 5. The computational analysis confirmed the important role of the GCP fragment and its protonation states in the sensing of polynucleotides and revealed that it is affected by the intrinsic dynamical features of conjugates themselves. Both conjugates showed a negligible response to uracil and cytosine ss-RNA as well as ds-RNA at pH 7, and only weak interactions with ds-DNA. Thus, nucleobase–GCP conjugates can be considered as novel lead compounds for the design of ss-RNA or ss-DNA selective fluorimetric probes. Full article
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Communication
From α-Bromomethylbutenolide to Fused Tri(Tetra) Cyclic Dihydrofurandiones through Barbier Reaction–Heck Arylation Sequence
Molecules 2017, 22(12), 2171; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22122171 - 08 Dec 2017
Cited by 1 | Viewed by 1893
Abstract
A Barbier reaction–Heck arylation sequence from α-bromomethylbutenolide to fused tri and tetracyclic lactones has been developed. The first step involving a Barbier reaction enabled installing ortho-bromoaromatics in α-ylidene γ-lactones. The latter substrates were subjected to intramolecular Heck reaction conditions which selectively afforded [...] Read more.
A Barbier reaction–Heck arylation sequence from α-bromomethylbutenolide to fused tri and tetracyclic lactones has been developed. The first step involving a Barbier reaction enabled installing ortho-bromoaromatics in α-ylidene γ-lactones. The latter substrates were subjected to intramolecular Heck reaction conditions which selectively afforded 6,5,5 or 6,6,5 fused ring systems depending on the nature of the base employed. Full article
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Article
Multi Component Reactions under Increased Pressure: On the Mechanism of Formation of Pyridazino[5,4,3-de][1,6]naphthyridine Derivatives by the Reaction of Malononitrile, Aldehydes and 2-Oxoglyoxalarylhydrazones in Q-Tubes
Molecules 2017, 22(12), 2114; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22122114 - 01 Dec 2017
Cited by 4 | Viewed by 2355
Abstract
Efficient synthesis of phenanthridin-6(5H)-one derivatives 12an in a four-component reaction of aldehyde hydrazone, aromatic aldehydes and malononitrile in Q-Tubes is reported. The results showed that the methodology has the advantage of being a one-pot synthesis of tricyclic systems in [...] Read more.
Efficient synthesis of phenanthridin-6(5H)-one derivatives 12an in a four-component reaction of aldehyde hydrazone, aromatic aldehydes and malononitrile in Q-Tubes is reported. The results showed that the methodology has the advantage of being a one-pot synthesis of tricyclic systems in good yields. Potential routes leading to formation of compounds 12 are discussed. The structures of the synthesized compounds could be unequivocally established via X-ray crystal structure determination and spectroscopic methods. Full article
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Article
A New Synthetic Route to Polyhydrogenated Pyrrolo[3,4-b]pyrroles by the Domino Reaction of 3-Bromopyrrole-2,5-Diones with Aminocrotonic Acid Esters
Molecules 2017, 22(11), 2035; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22112035 - 22 Nov 2017
Viewed by 2109
Abstract
A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-b]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular [...] Read more.
A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-b]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular nucleophilic addition without recyclyzation of imide cycle. Full article
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Article
Synthesis of Novel Glycerol-Derived 1,2,3-Triazoles and Evaluation of Their Fungicide, Phytotoxic and Cytotoxic Activities
Molecules 2017, 22(10), 1666; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22101666 - 07 Oct 2017
Cited by 13 | Viewed by 2876
Abstract
The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal [...] Read more.
The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicidal activity was assessed in vitro against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)-cyclo-hexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency in controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a promising scaffold to be explored for the development of new agents to control C. gloeosporioides. Full article
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Article
Hydrogen-Bonding Interactions in Luminescent Quinoline-Triazoles with Dominant 1D Crystals
Molecules 2017, 22(10), 1600; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22101600 - 22 Sep 2017
Cited by 2 | Viewed by 2718
Abstract
Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal [...] Read more.
Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal direction of growth. Crystals of 13 are 1D tape and prism shapes that correlate with their intermolecular and solvent 1D lattice H-bonding interactions. All compounds were thermally stable up to about 200 C and blue-green emissive in solution. Full article
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Article
A Facile Oxidative Opening of the C-Ring in Luotonin A and Derivatives
Molecules 2017, 22(9), 1540; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22091540 - 12 Sep 2017
Cited by 5 | Viewed by 2160
Abstract
An oxidative ring opening reaction of the central ring C in the alkaloid Luotonin A and two of its derivatives was found to occur upon heating with an excess amine and potassium carbonate in dimethylsulfoxide (DMSO) solution in the presence of air oxygen. [...] Read more.
An oxidative ring opening reaction of the central ring C in the alkaloid Luotonin A and two of its derivatives was found to occur upon heating with an excess amine and potassium carbonate in dimethylsulfoxide (DMSO) solution in the presence of air oxygen. The structure of the novel amide-type products was elucidated and a possible mechanism for this reaction is proposed. Four of the new compounds show moderate in vitro anticancer activity towards human colon adenocarcinoma cells. Full article
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Article
Synthesis and DFT Calculations of Novel Vanillin-Chalcones and Their 3-Aryl-5-(4-(2-(dimethylamino)-ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde Derivatives as Antifungal Agents
Molecules 2017, 22(9), 1476; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22091476 - 05 Sep 2017
Cited by 11 | Viewed by 3298
Abstract
Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction [...] Read more.
Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction was carried out in formic acid. The antifungal activity of both series of compounds against eight fungal species was determined. In general, chalcone derivatives 4 showed better activities than pyrazolines 5 against all tested fungi. None of the compounds 4ag and 5ag showed activity against the three Aspergillus spp. In contrast, most of the compounds 4 showed moderate to high activities against three dermatophytes (MICs 31.25–62.5 µg/mL), being 4a followed by 4c the most active structures. Interestingly, 4a and 4c possess fungicidal rather than fungistatic activities, with MFC values between 31.25 and 62.5 μg/mL. The comparison of the percentages of inhibition of C. neoformans by the most active compounds 4, allowed us to know the role played by the different substituents of the chalcones’ A-ring. Also the most anti-cryptococcal compounds 4ac and 4g, were tested in a second panel of five clinical C. neoformans strains in order to have an overview of their inhibition capacity not only of standardized but also of clinical C. neoformans strains. DFT calculations showed that the electrophilicity is the main electronic property to explain the differences in antifungal activities for the synthesized chalcones and pyrazolines compounds. Furthermore, a quantitative reactivity analysis showed that electron-withdrawing substituted chalcones presented the higher electrophilic character and hence, the greater antifungal activities among compounds of series 4. Full article
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Article
Voltammetric Study of Some 3-Aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide Derivatives with Anti-Tumor Activities
Molecules 2017, 22(9), 1442; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22091442 - 31 Aug 2017
Cited by 5 | Viewed by 2339
Abstract
The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible [...] Read more.
The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible or quasireversible and is attributed to reduction of the N-oxide moiety to form a radical anion. The second reduction of the diazine ring was found to be irreversible. Compounds containing a nitro group on the 3-phenyl ring also exhibited a reduction process that may be attributed to that group. There was good correlation between molecular structure and reduction potential, with reduction being facilitated by an enhanced net positive charge at the electroactive site created by electron withdrawing substituents. Additionally, the reduction potential was calculated using two common basis sets, 6-31g and lanl2dz, for five of the test molecules. There was a strong correlation between the computational data and the experimental data, with the exception of the derivative containing the nitro functionality. No relationship between the experimentally measured reduction potentials and reported cytotoxic activities was evident upon comparison of the data. Full article
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Article
Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe3+ Ions Sensing Properties
Molecules 2017, 22(9), 1417; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules22091417 - 29 Aug 2017
Cited by 4 | Viewed by 3581
Abstract
A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light [...] Read more.
A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light scattering (DLS) characterization revealed that the aggregates of receptor 1 at 80% water fraction have an average size of ≈142 nm. Field emission scanning electron microscopy (FE-SEM) analysis confirmed the formation of spherical aggregates upon solvent evaporation. The sensing properties of receptor 1 were investigated by UV-vis, fluorescence emission spectroscopy, and other optical methods. Among the tested metal ions, receptor 1 is capable of recognizing the Fe3+ ion selectively. The changes in spectral measurements were explained on the basis of complex formation. The composition of receptor 1 and Fe3+ ions was determined by using Job’s plot and found to be 1:1. The receptor 1–Fe3+ complex showed a reversible UV-vis response in the presence of EDTA. Full article
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