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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

Collection Editor
Prof. Dr. Richard A. Bunce

Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078-3071, USA
Website | E-Mail
Interests: heterocycles; antibacterial agents; anticancer agents; enzyme inhibitors; medicinal chemistry; drug discovery; drug development; synthetic methodology
Collection Editor
Prof. Dr. Philippe Belmont

School of Pharmacy, University Paris Descartes, UMR CNRS 8638, case 24. 4, avenue de l’Observatoire, 75006 Paris, France
E-Mail
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
Collection Editor
Prof. Dr. Wim Dehaen

Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium
Website | E-Mail
Phone: +32 16 32 74 39
Fax: +32 16 32 79 90
Interests: organic synthesis; heterocycles; supramolecular chemistry; porphyrin analogues; natural products; helicenes
Collection Editor
Prof. Dr. Eugene Babaev

Chemistry Department, Moscow State University, GSP-3, Moscow 119991, Russia
Website | E-Mail
Interests: heterocyclic chemistry; periodic table

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 1800 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 (86 papers)

2018

Jump to: 2017, 2016, 2015

Open AccessArticle Synthesis, Spectroscopic Characterization, and In Vitro Antibacterial Evaluation of Novel Functionalized Sulfamidocarbonyloxyphosphonates
Molecules 2018, 23(7), 1682; https://doi.org/10.3390/molecules23071682
Received: 18 June 2018 / Revised: 4 July 2018 / Accepted: 5 July 2018 / Published: 10 July 2018
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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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Open AccessCorrection 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://doi.org/10.3390/molecules23071592
Received: 26 June 2018 / Accepted: 28 June 2018 / Published: 29 June 2018
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Abstract
The authors wish to make the following changes to their paper [1].[...] Full article
Open AccessArticle Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines
Molecules 2018, 23(6), 1280; https://doi.org/10.3390/molecules23061280
Received: 28 April 2018 / Revised: 17 May 2018 / Accepted: 22 May 2018 / Published: 26 May 2018
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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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Open AccessArticle 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://doi.org/10.3390/molecules23051024
Received: 22 March 2018 / Revised: 23 April 2018 / Accepted: 23 April 2018 / Published: 27 April 2018
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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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Open AccessArticle 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://doi.org/10.3390/molecules23030693
Received: 25 February 2018 / Revised: 13 March 2018 / Accepted: 16 March 2018 / Published: 19 March 2018
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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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Open AccessFeature PaperArticle 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://doi.org/10.3390/molecules23030674
Received: 23 February 2018 / Revised: 13 March 2018 / Accepted: 14 March 2018 / Published: 16 March 2018
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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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Open AccessArticle 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://doi.org/10.3390/molecules23030592
Received: 14 February 2018 / Revised: 26 February 2018 / Accepted: 4 March 2018 / Published: 6 March 2018
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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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Open AccessArticle Synthesis and Optical Properties of Near-Infrared meso-Phenyl-Substituted Symmetric Heptamethine Cyanine Dyes
Molecules 2018, 23(2), 226; https://doi.org/10.3390/molecules23020226
Received: 27 November 2017 / Revised: 18 January 2018 / Accepted: 20 January 2018 / Published: 24 January 2018
Cited by 1 | PDF Full-text (1200 KB) | HTML Full-text | XML Full-text | Supplementary Files
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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Open AccessArticle Regioselectivity in Reactions between Bis(2-benzothiazolyl)ketone and Vinyl Grignard Reagents: C- versus O-alkylation—Part III
Molecules 2018, 23(1), 171; https://doi.org/10.3390/molecules23010171
Received: 20 December 2017 / Revised: 10 January 2018 / Accepted: 12 January 2018 / Published: 15 January 2018
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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

Jump to: 2018, 2016, 2015

Open AccessArticle Energetic Di- and Trinitromethylpyridines: Synthesis and Characterization
Received: 6 November 2017 / Revised: 9 December 2017 / Accepted: 18 December 2017 / Published: 21 December 2017
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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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Open AccessArticle Nucleobase–Guanidiniocarbonyl-Pyrrole Conjugates as Novel Fluorimetric Sensors for Single Stranded RNA
Molecules 2017, 22(12), 2213; https://doi.org/10.3390/molecules22122213
Received: 1 November 2017 / Revised: 4 December 2017 / Accepted: 9 December 2017 / Published: 13 December 2017
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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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Open AccessCommunication From α-Bromomethylbutenolide to Fused Tri(Tetra) Cyclic Dihydrofurandiones through Barbier Reaction–Heck Arylation Sequence
Molecules 2017, 22(12), 2171; https://doi.org/10.3390/molecules22122171
Received: 30 October 2017 / Revised: 5 December 2017 / Accepted: 7 December 2017 / Published: 8 December 2017
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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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Open AccessArticle 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://doi.org/10.3390/molecules22122114
Received: 16 October 2017 / Revised: 27 November 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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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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Open AccessArticle 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://doi.org/10.3390/molecules22112035
Received: 4 November 2017 / Revised: 16 November 2017 / Accepted: 20 November 2017 / Published: 22 November 2017
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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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Open AccessArticle Synthesis of Novel Glycerol-Derived 1,2,3-Triazoles and Evaluation of Their Fungicide, Phytotoxic and Cytotoxic Activities
Molecules 2017, 22(10), 1666; https://doi.org/10.3390/molecules22101666
Received: 1 September 2017 / Revised: 29 September 2017 / Accepted: 3 October 2017 / Published: 7 October 2017
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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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Open AccessArticle Hydrogen-Bonding Interactions in Luminescent Quinoline-Triazoles with Dominant 1D Crystals
Molecules 2017, 22(10), 1600; https://doi.org/10.3390/molecules22101600
Received: 24 August 2017 / Revised: 14 September 2017 / Accepted: 15 September 2017 / Published: 22 September 2017
Cited by 1 | PDF Full-text (3524 KB) | HTML Full-text | XML Full-text | Supplementary Files
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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Open AccessArticle A Facile Oxidative Opening of the C-Ring in Luotonin A and Derivatives
Molecules 2017, 22(9), 1540; https://doi.org/10.3390/molecules22091540
Received: 7 August 2017 / Revised: 11 September 2017 / Accepted: 11 September 2017 / Published: 12 September 2017
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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.
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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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Open AccessArticle 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://doi.org/10.3390/molecules22091476
Received: 8 August 2017 / Revised: 31 August 2017 / Accepted: 31 August 2017 / Published: 5 September 2017
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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
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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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Open AccessArticle 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://doi.org/10.3390/molecules22091442
Received: 9 August 2017 / Revised: 28 August 2017 / Accepted: 29 August 2017 / Published: 31 August 2017
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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
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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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Open AccessArticle Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe3+ Ions Sensing Properties
Molecules 2017, 22(9), 1417; https://doi.org/10.3390/molecules22091417
Received: 19 July 2017 / Revised: 17 August 2017 / Accepted: 21 August 2017 / Published: 29 August 2017
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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
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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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Open AccessArticle Covalent Porphyrin Hybrids Linked with Dipyrrin, Bidipyrrin or Thiacorrole
Molecules 2017, 22(9), 1400; https://doi.org/10.3390/molecules22091400
Received: 3 August 2017 / Revised: 19 August 2017 / Accepted: 20 August 2017 / Published: 23 August 2017
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Abstract
Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin
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Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin nickel complex 3 was successfully obtained in a high yield by the oxidation of porphyrinyl dipyrromethane 2 and subsequent coordination. Further oxidative coupling reactions of 3 afforded por-bidipyrrin-por hybrid 4. Interestingly, an unexpected methoxy por-bidipyrrin-por hybrid 6 was generated by treating 4 with FeCl3 in CH2Cl2/MeOH and subsequent coordination. In addition to open chain hybrids, an aromatic scaffold hybrid por-thiacorrole-por 8 was synthesized by treating porphyrinyl dibromo-dipyrrin nickel complex 7 with Na2S·9H2O. A series of porphyrin hybrids offers a new approach for π-conjugated molecules. Full article
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Open AccessArticle Tetrabutylammonium Iodide–Promoted Thiolation of Oxindoles Using Sulfonyl Chlorides as Sulfenylation Reagents
Molecules 2017, 22(8), 1208; https://doi.org/10.3390/molecules22081208
Received: 11 July 2017 / Revised: 26 July 2017 / Accepted: 28 July 2017 / Published: 1 August 2017
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Abstract
3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition-metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation reagents. The above reaction was promoted by iodide anions, which was ascribed to the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl iodides. Moreover, the thiolation
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3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition-metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation reagents. The above reaction was promoted by iodide anions, which was ascribed to the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl iodides. Moreover, the thiolation of 3-aryloxindoles was facilitated by bases. The use of a transition-metal-free protocol, readily available reagents, and mild reaction conditions make this protocol more practical for preparing 3-sulfanyloxindoles than traditional methods. Full article
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Open AccessArticle Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles
Molecules 2017, 22(7), 1211; https://doi.org/10.3390/molecules22071211
Received: 7 June 2017 / Revised: 8 July 2017 / Accepted: 17 July 2017 / Published: 20 July 2017
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Abstract
A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d
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A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC50 values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC50 = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results. Full article
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Open AccessArticle Study on the Alkylation Reactions of N(7)-Unsubstituted 1,3-Diazaoxindoles
Molecules 2017, 22(5), 846; https://doi.org/10.3390/molecules22050846
Received: 9 April 2017 / Revised: 13 May 2017 / Accepted: 16 May 2017 / Published: 19 May 2017
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Abstract
The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were
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The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized. Full article
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Open AccessArticle One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and Mechanistic Study
Molecules 2017, 22(5), 820; https://doi.org/10.3390/molecules22050820
Received: 18 March 2017 / Revised: 11 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
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Abstract
A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions
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A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions thus involved Vilsmeier amidination, imination reactions, and the sequential intermolecular heterocyclization. To study the reaction mechanism, a series of 4-formyl-1,3-diphenyl-1H-pyrazol-5-yl-N,N-disubstituted formamidines, which were conceived as the chemical equivalent of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl-formamidine, were prepared and successfully converted into pyrazolo[3,4-d]pyrimidines. The experiments demonstrated that the reaction intermediates were the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl)formamidines. The rate of the reaction could be described as being proportional to the reactivity of amine reactants during intermolecular heterocyclization, especially when hexamethyldisilazane was used. Full article
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Open AccessArticle Ortho-Nitro Effect on the Diastereoselective Control in Sulfa-Staudinger and Staudinger Cycloadditions
Molecules 2017, 22(5), 784; https://doi.org/10.3390/molecules22050784
Received: 6 February 2017 / Revised: 8 May 2017 / Accepted: 9 May 2017 / Published: 12 May 2017
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Abstract
The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver cis-β-sultams in considerable amounts, together with the predominant trans
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The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver cis-β-sultams in considerable amounts, together with the predominant trans-β-sultams. In other cases, the above sulfa-Staudinger cycloadditions give rise to trans-β-sultams exclusively. Further mechanistic rationalization discloses that the ortho-nitro effect is attributed to its strong electron-withdrawing inductive effect. Similarly, the ortho-nitro effect also exists in Staudinger cycloadditions of ethoxycarbonyl ketene with the imines. The current research provides further insights into the diastereoselective control in sulfa-Staudinger and Staudinger cycloadditions. Full article
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Open AccessArticle Rhodium(I)-Complexes Catalyzed 1,4-Conjugate Addition of Arylzinc Chlorides to N-Boc-4-pyridone
Molecules 2017, 22(5), 723; https://doi.org/10.3390/molecules22050723
Received: 15 March 2017 / Revised: 27 April 2017 / Accepted: 27 April 2017 / Published: 1 May 2017
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Abstract
Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C2H4)2]2 and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition
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Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C2H4)2]2 and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition reactions of arylzinc chlorides to N-Boc-4-pyridone. A broad scope of arylzinc reagents with both electron-withdrawing and electron-donating substituents on the aromatic ring successfully underwent 1,4-conjugate addition to N-Boc-4-pyridone to afford versatile 1,4-adducts 2-substituted-2,3-dihydropyridones in good to excellent yields (up to 91%) and excellent ee (up to 96%) when (S)-BINAP was used as chiral ligand. Full article
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Open AccessArticle Reactions of 5-Indolizyl Lithium Compounds with Some Bielectrophiles
Molecules 2017, 22(4), 661; https://doi.org/10.3390/molecules22040661
Received: 3 March 2017 / Revised: 9 April 2017 / Accepted: 17 April 2017 / Published: 20 April 2017
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Abstract
Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl pyruvate giving 1,2-hydroxyacid. However, with α-halocarbonyl compounds, they react in different ways, forming the products of selective bromination at C-5 (with α-bromo
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Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl pyruvate giving 1,2-hydroxyacid. However, with α-halocarbonyl compounds, they react in different ways, forming the products of selective bromination at C-5 (with α-bromo ketones and esters of α-bromo acids) and 5-chloroacetyl indolizines. Full article
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Open AccessArticle Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone Motif-Fused 3,3′-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition Reaction
Molecules 2017, 22(4), 645; https://doi.org/10.3390/molecules22040645
Received: 23 March 2017 / Revised: 11 April 2017 / Accepted: 13 April 2017 / Published: 17 April 2017
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Abstract
Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products
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Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products bearing four or three consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable application of this method was for the design of new hybrid architectures for biological screening through the adequate fusion of these sub-units of turmerone and 3,3′-pyrrolidinyl-dispirooxindole, generating drug-like molecules. Full article
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Open AccessArticle Consecutive One-Pot versus Domino Multicomponent Approaches to 3-(Diarylmethylene)oxindoles
Molecules 2017, 22(3), 503; https://doi.org/10.3390/molecules22030503
Received: 27 February 2017 / Revised: 9 March 2017 / Accepted: 17 March 2017 / Published: 22 March 2017
Cited by 2 | PDF Full-text (4684 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Based on consecutive one-pot conditions combining three palladium-catalyzed reactions (Sonogashira, Heck and Suzuki-Miyaura reactions), a more efficient domino multicomponent method has been successfully developed to access a wide variety of 3-(diarylmethylene)oxindoles. Microwave irradiation and use of a silver salt were the most important
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Based on consecutive one-pot conditions combining three palladium-catalyzed reactions (Sonogashira, Heck and Suzuki-Miyaura reactions), a more efficient domino multicomponent method has been successfully developed to access a wide variety of 3-(diarylmethylene)oxindoles. Microwave irradiation and use of a silver salt were the most important factors to achieve high yields and stereoselectivity. Full article
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Open AccessArticle Design of New Benzo[h]chromene Derivatives: Antitumor Activities and Structure-Activity Relationships of the 2,3-Positions and Fused Rings at the 2,3-Positions
Molecules 2017, 22(3), 479; https://doi.org/10.3390/molecules22030479
Received: 27 January 2017 / Revised: 11 March 2017 / Accepted: 13 March 2017 / Published: 18 March 2017
Cited by 4 | PDF Full-text (2384 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel 4H-benzo[h]chromenes 4, 611, 13, 14; 7H-benzo[h]chromeno[2,3-d]pyrimidines 1518, 20, and 14H-benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives
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A series of novel 4H-benzo[h]chromenes 4, 611, 13, 14; 7H-benzo[h]chromeno[2,3-d]pyrimidines 1518, 20, and 14H-benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 19ae, 24 was prepared. The structures of the synthesized compounds were characterized on the basis of their spectral data. Some of the target compounds were examined for their antiproliferative activity against three cell lines; breast carcinoma (MCF-7), human colon carcinoma (HCT-116) and hepatocellular carcinoma (HepG-2). The cytotoxic behavior has been tested using MTT assay and the inhibitory activity was referenced to three standard anticancer drugs: vinblastine, colchicine and doxorubicin. The bioassays demonstrated that some of the new compounds exerted remarkable inhibitory effects as compared to the standard drugs on the growth of the three tested human tumor cell lines. The structure–activity relationships (SAR) study highlights that the antitumor activity of the target compounds was significantly affected by the lipophilicity of the substituent at 2- or 3- and fused rings at the 2,3-positions. Full article
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Open AccessArticle Facial Regioselective Synthesis of Novel Bioactive Spiropyrrolidine/Pyrrolizine-Oxindole Derivatives via a Three Components Reaction as Potential Antimicrobial Agents
Molecules 2017, 22(3), 357; https://doi.org/10.3390/molecules22030357
Received: 9 January 2017 / Revised: 19 February 2017 / Accepted: 24 February 2017 / Published: 26 February 2017
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Abstract
This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6aj and spirooxindole-spiropiperidinone-pyrrolizines 8aj, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4aj. All
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This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6aj and spirooxindole-spiropiperidinone-pyrrolizines 8aj, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4aj. All of the newly synthesized compounds were evaluated for their antimicrobial activities and their minimum inhibitory concentration (MIC) against most of the test organisms. The tested compounds displayed excellent activity against all of the tested microorganisms. Full article
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Open AccessArticle Diastereoselective Synthesis of Spirocyclopropanes under Mild Conditions via Formal [2 + 1] Cycloadditions Using 2,3-Dioxo-4-benzylidene-pyrrolidines
Molecules 2017, 22(2), 328; https://doi.org/10.3390/molecules22020328
Received: 16 January 2017 / Revised: 14 February 2017 / Accepted: 16 February 2017 / Published: 22 February 2017
Cited by 1 | PDF Full-text (2243 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A highly diastereoselective cyclopropanation of cyclic enones with sulfur ylides was developed under catalyst-free conditions, producing multifunctional spirocyclopropanes in generally excellent yields (up to 99% yield and >99:1 d.r.). The asymmetric version of this method was realized by using an easily available chiral
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A highly diastereoselective cyclopropanation of cyclic enones with sulfur ylides was developed under catalyst-free conditions, producing multifunctional spirocyclopropanes in generally excellent yields (up to 99% yield and >99:1 d.r.). The asymmetric version of this method was realized by using an easily available chiral sulfur ylide, affording products with moderate to good stereoselectivity. Full article
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Open AccessArticle Cytotoxicity and Antioxidant Potential of Novel 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole Derivatives
Molecules 2017, 22(2), 260; https://doi.org/10.3390/molecules22020260
Received: 4 January 2017 / Revised: 1 February 2017 / Accepted: 7 February 2017 / Published: 9 February 2017
Cited by 6 | PDF Full-text (5184 KB) | HTML Full-text | XML Full-text
Abstract
Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC50
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Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC50: 11.6 μM (1), and 12.4 μM (3)] and HeLa [IC50: 22.4 μM (1) and 19.4μM (3)] cell lines is reported. Their antioxidant potential was evaluated by spectrophotometric method, using DPPH radical or Fe (TPTZ)3+ complex, and EPR spectroscopy, therefore the compounds 1 and 3 showed remarkable antioxidant activity simultaneously with a cytotoxic effect on A2780 and HeLa cell lines. Furthermore, based on theoretical quantum chemical calculation, the present study analyzed the chemoselectivity of the hydrogen extraction from the indolyl-hydrazinil-thiazoles in reaction with free radicals. Full article
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Open AccessArticle Novel 2,3-Dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones: Synthesis and Biological Evaluation
Received: 8 December 2016 / Revised: 21 December 2016 / Accepted: 28 December 2016 / Published: 30 December 2016
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Abstract
Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum.
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Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The title compounds were prepared via PdCl2-mediated endo-dig cyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1H)-ones. The latter were prepared, in turn, via initial Sonogashira cross-coupling of 2-amino-5-bromo-3-iodobenzamide with aryl acetylenes followed by boric acid-mediated cyclocondensation of the intermediate 2-amino-3-(arylethynyl)-5-bromobenzamides with benzaldehyde derivatives. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4ak were evaluated for potential in vitro cytotoxicity against the breast (MCF-7), melanoma (B16) and endothelioma (sEnd.2) cell lines. All of the compounds except 4h and 4i were found to be inactive against the three cancer cell lines. Compound 4h substituted with a 4-methoxyphenyl and 4-fluorophenyl groups at the 3- and 5-positions was found to exhibit significant cytotoxicity against the three cancer cell lines. The presence of phenyl and 3-chlorophenyl groups at the 3- and 5-posiitons of the pyrroloquinazolinone 4i, on the other hand, resulted in significant cytotoxicity against vascular tumour endothelial cells (sEnd.2), but reduced activity against the melanoma (B16) and breast cancer (MCF-7) cells except at higher concentrations. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4al were found to be inactive against the chloroquine sensitive 3D7 strain of Plasmodium falciparum. Full article
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Open AccessArticle Facile Synthesis for Benzo-1,4-Oxazepine Derivatives by Tandem Transformation of C-N Coupling/C-H Carbonylation
Received: 21 November 2016 / Revised: 22 December 2016 / Accepted: 28 December 2016 / Published: 30 December 2016
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Abstract
A tandem transformation of C-N coupling/C-H carbonylation has been developed for the synthesis of benzo-1,4-oxazepine pharmaceutically derivatives. Notably, this reaction was accomplished by various phenylamine with ally halides under carbon dioxide atmosphere employing 2-(2-dimethylamino-vinyl)-1H-inden-1-olcatalyzed. Furthermore, under the optimized conditions, various benzo-1,4-oxazepine
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A tandem transformation of C-N coupling/C-H carbonylation has been developed for the synthesis of benzo-1,4-oxazepine pharmaceutically derivatives. Notably, this reaction was accomplished by various phenylamine with ally halides under carbon dioxide atmosphere employing 2-(2-dimethylamino-vinyl)-1H-inden-1-olcatalyzed. Furthermore, under the optimized conditions, various benzo-1,4-oxazepine derivatives were obtained in good yields. Finally, a plausible CuI/CuIII mechanism of C-N coupling/C-H carbonylation transformation was proposed. Full article
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Open AccessArticle A Metal-Free Regioselective Multicomponent Approach for the Synthesis of Free Radical Scavenging Pyrimido-Fused Indazoles and Their Fluorescence Studies
Molecules 2016, 21(11), 1571; https://doi.org/10.3390/molecules21111571
Received: 23 September 2016 / Revised: 8 November 2016 / Accepted: 11 November 2016 / Published: 18 November 2016
Cited by 3 | PDF Full-text (2326 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study deals with a new and efficient metal-free regioselective synthesis of pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b
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This study deals with a new and efficient metal-free regioselective synthesis of pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b]indazole analogues. Response Surface Methodology (RSM) coupled with a Box-Behnken design (BBD) were utilized for exploring the effect of base used (A), temperature of reaction (B) and (C), reaction time. This approach can allow access to a variety of pyrimidoindazole fluorophores and related compounds. The compound N,N-dimethyl-4-(2-phenylpyrimido[1,2-b]indazol-4-yl)aniline (4e) displays the maximum fluorescence intensity at 518 nm and shows a fluorescence quantum yield of 0.068. The synthesized pyramido-fused indazoles have been evaluated for their free radical scavenging activity and compound 4f showed good antioxidant activity. Full article
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Open AccessArticle Practical and Metal-Free Synthesis of Novel Enantiopure Amides Containing the Potentially Bioactive 5-Nitroimidazole Moiety
Molecules 2016, 21(11), 1472; https://doi.org/10.3390/molecules21111472
Received: 30 September 2016 / Revised: 26 October 2016 / Accepted: 28 October 2016 / Published: 4 November 2016
Cited by 1 | PDF Full-text (1077 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine
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We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles. Full article
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Open AccessArticle Structural Characterization and Antimicrobial Activities of 7H-Benzo[h]chromeno[2,3-d]pyrimidine and 14H-Benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c] pyrimidine Derivatives
Molecules 2016, 21(11), 1450; https://doi.org/10.3390/molecules21111450
Received: 30 September 2016 / Revised: 22 October 2016 / Accepted: 28 October 2016 / Published: 1 November 2016
Cited by 3 | PDF Full-text (2567 KB) | HTML Full-text | XML Full-text
Abstract
Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7ao, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8ab
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Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7ao, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8ab and 3-ethoxycarbonyl-14-(4-halophenyl)-12-methoxy-14H-benzo-[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-one derivatives 12ab. The structure of these novel compounds were confirmed using IR, 1H- and 13C-NMR as well as MS spectroscopy. The new compounds were evaluated in vitro for their antimicrobial activity and it was demonstrated that 7H-benzochromenopyrimidine and derivatives of 14H-benzochromenotriazolopyrimidine exhibited the most promising antibacterial activities compared to the reference antimicrobial agents. The structure activity relationship (SAR) studies of the target compounds agreed with the in vitro essays and confirmed higher potent antimicrobial activity against some of the tested microorganisms. Full article
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Open AccessArticle Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines
Molecules 2016, 21(10), 1366; https://doi.org/10.3390/molecules21101366
Received: 30 August 2016 / Revised: 30 September 2016 / Accepted: 6 October 2016 / Published: 14 October 2016
Cited by 3 | PDF Full-text (2636 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps.
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Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps. The 4-anilinoquinazolines were evaluated for potential cytotoxicity against three cancer cell lines, namely, human breast adenocarcinoma (MCF-7) cells, human cervical cancer (HeLa) and human lung cancer (A549) cells. The most active compounds, 2b, 2c, 3c, 4a, 4c and 5a, were found to be more selective against the MCF-7 and HeLa cell lines than the human lung carcinoma (A549) cells. We selected compounds 2c, 3c and 7a as representatives for further evaluation for potential to induce apoptosis and/or necrotic properties in the three cancer cell lines. Compound 2c induced apoptosis of MCF-7 cells through cell membrane alteration. Treatment of Hela and A549 cell lines with compounds 3c and 7a, respectively, led to caspase-3 activation in both cell lines. Compound 3c, on the other hand, caused more necrosis than apoptosis induction in the membrane alteration assay. Full article
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Open AccessCommunication Nucleophilic Substitution on 2-Monosubstituted Quinoxalines Giving 2,3-Disubstituted Quinoxalines: Investigating the Effect of the 2-Substituent
Molecules 2016, 21(10), 1304; https://doi.org/10.3390/molecules21101304
Received: 30 August 2016 / Revised: 15 September 2016 / Accepted: 23 September 2016 / Published: 30 September 2016
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Abstract
An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields.
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An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields. 2-Monosubstituted quinoxalines bearing a phenyl and butyl substituent reacted readily with alkyl-, aryl-, heteroaryl- and alkynyl- nucluephiles, giving di-substituted quinoxalines. 2-Monosubstituted quinoxalines bearing an amine and alkynyl substituent only reacted with alkyl nucleophiles. Oxidative rearomatization to give 2,3-disubstituted quinoxaline products occurred in atmospheric O2. Full article
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Open AccessArticle Optimized Conditions for Passerini-Smiles Reactions and Applications to Benzoxazinone Syntheses
Molecules 2016, 21(9), 1257; https://doi.org/10.3390/molecules21091257
Received: 27 July 2016 / Revised: 13 September 2016 / Accepted: 13 September 2016 / Published: 21 September 2016
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Abstract
Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between
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Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between electron-poor phenols, isocyanides, and carbonyl derivatives. These new conditions have been applied to several synthetic strategies towards benzoxazinones. Full article
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Open AccessArticle Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines
Molecules 2016, 21(8), 1072; https://doi.org/10.3390/molecules21081072
Received: 25 June 2016 / Revised: 9 August 2016 / Accepted: 10 August 2016 / Published: 17 August 2016
Cited by 3 | PDF Full-text (1615 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly
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A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their antimicrobial activity against various microorganisms. Full article
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Open AccessReview Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives
Molecules 2016, 21(8), 1032; https://doi.org/10.3390/molecules21081032
Received: 17 June 2016 / Revised: 29 July 2016 / Accepted: 29 July 2016 / Published: 9 August 2016
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Abstract
This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc.
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This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc. Green syntheses and solvent-free procedures have been introduced whenever possible. The syntheses discussed herein have been selected to illustrate the huge potential of microwave in the synthesis of highly functionalized molecules with potential therapeutic applications, in high yields, enhanced reaction rates and increased chemoselectivity, compared to conventional methods. More than 100 references from the recent literature are listed in this review. Full article
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Open AccessReview Recent Advances in Metal-Free Quinoline Synthesis
Molecules 2016, 21(8), 986; https://doi.org/10.3390/molecules21080986
Received: 27 June 2016 / Revised: 21 July 2016 / Accepted: 22 July 2016 / Published: 29 July 2016
Cited by 27 | PDF Full-text (12785 KB) | HTML Full-text | XML Full-text
Abstract
The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes.
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The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. Quinolines were first synthesized in 1879, and since then a multitude of synthetic routes have been developed. Many of these methods, such as the Skraup, Doebner–Von Miller, and Friedlander quinoline syntheses, are well-known but suffer from inefficiency, harsh reaction conditions, and toxic reagents. This review focuses on recent transition metal-free processes toward these important heterocycles, including both novel routes and modifications to established methods. For example, variations on the Skraup method include microwave irradiation, ionic liquid media, and novel annulation partners, all of which have shown increased reaction efficiency and improved yield of the heteroring-unsubstituted quinoline products. Similarly, modifications to other synthetic routes have been implemented, with the quinoline products displaying a wide variety of substitution patterns. Full article
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Open AccessArticle Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives
Molecules 2016, 21(8), 967; https://doi.org/10.3390/molecules21080967
Received: 28 June 2016 / Revised: 19 July 2016 / Accepted: 20 July 2016 / Published: 23 July 2016
Cited by 1 | PDF Full-text (753 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The 1H- and 13C-NMR spectra
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A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The 1H- and 13C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra. Full article
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Open AccessArticle Synthesis of New 3-Heteroarylindoles as Potential Anticancer Agents
Molecules 2016, 21(7), 929; https://doi.org/10.3390/molecules21070929
Received: 25 May 2016 / Revised: 8 July 2016 / Accepted: 12 July 2016 / Published: 16 July 2016
Cited by 7 | PDF Full-text (1552 KB) | HTML Full-text | XML Full-text
Abstract
2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1
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2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones, respectively. Also, hydrazonoyl halides were reacted with N’-(1-(1H-indol-3-yl)ethylidene)-2-cyanoacetohydrazide to afford 1,3,4-thiadiazole derivatives. Structures of the new synthesis were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Fifteen of the new compounds have been evaluated for their antitumor activity against the MCF-7 human breast carcinoma cell line. The results indicated that many of the tested compounds showed moderate to high anticancer activity when compared with doxorubicin as a reference drug. Full article
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Open AccessArticle Dyeing of Polyester with Disperse Dyes: Part 2. Synthesis and Dyeing Characteristics of Some Azo Disperse Dyes for Polyester Fabrics
Molecules 2016, 21(7), 855; https://doi.org/10.3390/molecules21070855
Received: 22 May 2016 / Revised: 13 June 2016 / Accepted: 24 June 2016 / Published: 29 June 2016
Cited by 4 | PDF Full-text (713 KB) | HTML Full-text | XML Full-text
Abstract
The goal of this study was to utilize carrier for accelerating the rate of dyeing not only to enhance dyeing of polyester fabrics dyed with disperse dyes 3a,b, but also to save energy. Both the color strength expressed as dye
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The goal of this study was to utilize carrier for accelerating the rate of dyeing not only to enhance dyeing of polyester fabrics dyed with disperse dyes 3a,b, but also to save energy. Both the color strength expressed as dye uptake and the fastness properties of the dyed fabrics were evaluated. Full article
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Open AccessArticle Dual Behavior of Iodine Species in Condensation of Anilines and Vinyl Ethers Affording 2-Methylquinolines
Molecules 2016, 21(7), 827; https://doi.org/10.3390/molecules21070827
Received: 10 May 2016 / Revised: 15 June 2016 / Accepted: 21 June 2016 / Published: 25 June 2016
Cited by 1 | PDF Full-text (6782 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A metal-free, mild and efficient method for the synthesis of 2-methylquinolines was successfully developed by condensation of anilines with vinyl ethers in the presence of catalytic amount of iodine. Modification of both pyridine and benzene moieties was easily achieved by changing only the
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A metal-free, mild and efficient method for the synthesis of 2-methylquinolines was successfully developed by condensation of anilines with vinyl ethers in the presence of catalytic amount of iodine. Modification of both pyridine and benzene moieties was easily achieved by changing only the vinyl ether and aniline. In this reaction, the iodine species was revealed to show dual behavior; molecular iodine serves as an oxidant, while its reduced form, hydrogen iodide, activates the vinyl ether. The redox reaction between these iodine species enables the use of a catalytic amount of iodine in this synthetic method. Full article
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Open AccessArticle Synthesis of Bioactive 2-(Arylamino)thiazolo[5,4-f]-quinazolin-9-ones via the Hügershoff Reaction or Cu- Catalyzed Intramolecular C-S Bond Formation
Molecules 2016, 21(6), 794; https://doi.org/10.3390/molecules21060794
Received: 22 April 2016 / Revised: 12 June 2016 / Accepted: 13 June 2016 / Published: 18 June 2016
Cited by 4 | PDF Full-text (7280 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives (series 8, 10, 14 and 17) was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient
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A library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives (series 8, 10, 14 and 17) was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient multistep synthesis of the key 6-amino-3-cyclopropylquinazolin-4(3H)-one (3) has been reinvestigated and performed on a multigram scale from the starting 5-nitroanthranilic acid. The inhibitory potency of the final products was evaluated against five kinases involved in Alzheimer’s disease and showed that some molecules of the 17 series described in this paper are particularly promising for the development of novel multi-target inhibitors of kinases. Full article
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Open AccessReview Synthesis of Linearly Fused Benzodipyrrole Based Organic Materials
Molecules 2016, 21(6), 785; https://doi.org/10.3390/molecules21060785
Received: 20 May 2016 / Revised: 10 June 2016 / Accepted: 13 June 2016 / Published: 17 June 2016
Cited by 8 | PDF Full-text (11078 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this review is to give an overview of the synthetic methods to prepare different indolo[3,2-b]carbazoles and similar systems with a potential use in electro-optical devices such as OLEDs (organic light emitting diode), OPVs (organic photovoltaic) and OFETs (organic
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The objective of this review is to give an overview of the synthetic methods to prepare different indolo[3,2-b]carbazoles and similar systems with a potential use in electro-optical devices such as OLEDs (organic light emitting diode), OPVs (organic photovoltaic) and OFETs (organic field effect transistor). Some further modifications to the core units and their implications for specific applications are also discussed. Full article
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Open AccessArticle Design, Synthesis and Antifungal Activity of Novel Benzofuran-Triazole Hybrids
Molecules 2016, 21(6), 732; https://doi.org/10.3390/molecules21060732
Received: 20 April 2016 / Revised: 27 May 2016 / Accepted: 1 June 2016 / Published: 7 June 2016
Cited by 2 | PDF Full-text (1315 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic
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A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic fungi. The result indicated that the target compounds exhibited moderate to satisfactory activity. Furthermore, molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation. Full article
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Open AccessArticle Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines
Molecules 2016, 21(6), 724; https://doi.org/10.3390/molecules21060724
Received: 16 April 2016 / Revised: 22 May 2016 / Accepted: 27 May 2016 / Published: 3 June 2016
Cited by 1 | PDF Full-text (4851 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[
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A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3-dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5-amine using the B3LYP/6–31 G(d, p) method were found to agree well with their X-ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications. Full article
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Open AccessArticle Synthesis of Novel UV Absorbers Bisindolylmethanes and Investigation of Their Applications on Cotton-Based Textile Materials
Molecules 2016, 21(6), 718; https://doi.org/10.3390/molecules21060718
Received: 14 April 2016 / Revised: 25 May 2016 / Accepted: 27 May 2016 / Published: 3 June 2016
Cited by 2 | PDF Full-text (1590 KB) | HTML Full-text | XML Full-text
Abstract
Nowadays modified textiles, especially UV-protective, antibacterial and antimicrobial ones, have become the focus of great interest. In this study, several new UV absorbers, bis(indolyl)methane derivatives, were synthesized and grafted onto polyvinyl alcohol polymer (PVA). Their application properties on cotton-based textile materials were determined;
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Nowadays modified textiles, especially UV-protective, antibacterial and antimicrobial ones, have become the focus of great interest. In this study, several new UV absorbers, bis(indolyl)methane derivatives, were synthesized and grafted onto polyvinyl alcohol polymer (PVA). Their application properties on cotton-based textile materials were determined; the UV protection factor values of the modified fabrics were measured (UPF); and the antibacterial features of the fabrics were tested. Full article
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Open AccessArticle Hydrazino-methoxy-1,3,5-triazine Derivatives’ Excellent Corrosion Organic Inhibitors of Steel in Acidic Chloride Solution
Molecules 2016, 21(6), 714; https://doi.org/10.3390/molecules21060714
Received: 29 April 2016 / Revised: 27 May 2016 / Accepted: 27 May 2016 / Published: 1 June 2016
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Abstract
The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at
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The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at a low concentration of 25 ppm (95%). The number of hydrazino groups play an important role in the corrosion inhibition, where the two hydrazine groups increased the electrostatic interactions between the protonated tested compounds, the negatively charged steel surface resulted from the adsorption of the chloride anions, and the presence of the methoxy group made the compound more reliable for formation of film protection on the surface of steel through the lone pair of oxygen atoms. Electrochemical Impedance Spectroscopy (EIS) measurements suggested that the corrosion process of steel in presence of the hydrazino-s-triazine derivatives (TH3, DMeHT and DHMeT) were being controlled by the charge transfer reaction. Polarization curves indicated that the examined TH3, DMeHT and DHMeT behaved as mixed type inhibitors. Full article
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Open AccessArticle Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts
Molecules 2016, 21(6), 707; https://doi.org/10.3390/molecules21060707
Received: 12 April 2016 / Revised: 16 May 2016 / Accepted: 23 May 2016 / Published: 1 June 2016
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Abstract
Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by
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Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13C-CP/MAS and 15N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated. Full article
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Open AccessArticle A Convenient Synthesis of 3,7′-Bisindole Derivatives
Molecules 2016, 21(5), 638; https://doi.org/10.3390/molecules21050638
Received: 15 March 2016 / Revised: 5 May 2016 / Accepted: 6 May 2016 / Published: 17 May 2016
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Abstract
An efficient and convenient method to synthesize highly functionalized 3,7′-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient,
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An efficient and convenient method to synthesize highly functionalized 3,7′-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient, environmentally friendly approach for easy access to various novel 3,7′-bisindole derivatives in moderate to good yields. Full article
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Open AccessArticle Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines
Molecules 2016, 21(4), 514; https://doi.org/10.3390/molecules21040514
Received: 17 December 2015 / Revised: 8 April 2016 / Accepted: 13 April 2016 / Published: 21 April 2016
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Abstract
Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a.
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Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH+ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH+ subpopulation. Full article
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Open AccessArticle A Green Ultrasound Synthesis, Characterization and Antibacterial Evaluation of 1,4-Disubstituted 1,2,3-Triazoles Tethering Bioactive Benzothiazole Nucleus
Molecules 2016, 21(4), 505; https://doi.org/10.3390/molecules21040505
Received: 11 March 2016 / Revised: 8 April 2016 / Accepted: 12 April 2016 / Published: 18 April 2016
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Abstract
The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a–r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a–c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t
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The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a–r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a–c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t-BuOH/H2O (1:1, v/v) as reaction solvents and CuSO4·5H2O/sodium ascorbate as the catalyst. The copper catalyst was implemented to provide the regioselective 1,4-disubstituted 1,2,3-triazoles 5a–r. Significant reductions in reaction times with comparably higher yields were observed when the reactions were carried out under ultrasound irradiation. The structures of the newly synthesized 1,2,3-triazoles were elucidated by IR, NMR, MS, and elemental analyses. They were also screened for their antimicrobial activity against three gram-positive (Streptococcus pneumonia, Bacillus subtilis, and Staphylococcus aureus), three gram-negative (Pseudomonas aeuroginosa, Escherichia coli, and Klebsiella pneumonia), and two fungal strains (Aspergillus fumigates and Candida albicans). Most of the tested compounds displayed promising antimicrobial activities at a Minimum Inhibition Concentration (MIC) of 4–16 μg/mL. Full article
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Open AccessReview Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues
Molecules 2016, 21(4), 492; https://doi.org/10.3390/molecules21040492
Received: 22 February 2016 / Revised: 31 March 2016 / Accepted: 5 April 2016 / Published: 14 April 2016
Cited by 9 | PDF Full-text (16808 KB) | HTML Full-text | XML Full-text
Abstract
This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity,
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This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed. Full article
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