Ether Derivatives Research Articles

Sea buckthorn leaf L-quebrachitol extract for improved glucose and lipid metabolism in insulin resistant hepG2 cells

L-quebrachitol is a natural monomethyl ether derivative of inositol, and it is abundant in sea buckthorn leaves. In this study, the potential efficacy on hepatic glucose, lipid metabolism disorder, and damaged pathway in vitro of sea buckthorn leaf L-quebrachitol extract (SQE) and L-quebrachitol standard (QS) was evaluated. The SQE and QS exhibited good inhibitory activity on α-amylase, and the kinetic study revealed that their type of enzyme inhibition was competitive inhibition in each case. Both QS and SQE increased the glucose consumption and decreased the contents of total triglyceride (TG) and non-esterified fatty acid (NEFA) in HepG2 cells displaying insulin resistance (IR). In addition, QS and SQE attenuated the expression levels of G6Pase and enhanced the expression of PPARα. These findings suggested that QS and SQE contributed to the modulation of glucose and lipid metabolism, and they might be a promising functional food additives and pharmaceuticals against Type 2 diabetes mellitus (T2DM).

Copper-Catalyzed Direct Allenylation of Inactive Cyclic Ethers.

We report here a direct allenylation reaction of inactive cyclic ethers. The reaction proceeds through a copper-catalyzed 1,4-difunctionalization of 1,3-enynes, with cyano group installed at the allenes simultaneously. This methodology shows a broad functional group compatibility to 1,3-enynes. Diversified allene-modified cyclic ether derivatives were synthesized with high regioselectivity under mild conditions.

Dipyridylmethane Ethers as Ligands for Luminescent Ir Complexes.

This work reports two new cationic heteroleptic cyclometalated iridium complexes, containing ether derivatives of di(pyridin-2-yl)methanol. The new ligands are based on dipyridin-2-ylmethane and are designed to obtain ether-based intermediates with extended electronic conjugation by insertion of π system such as phenyl, allyl and ethynyl. Different synthetic strategies were employed to introduce these units, as molecular wires, between the dipyridin-2-ylmethane chelating portion and the terminal N-containing functional group, such as amine and carbamide. The corresponding complexes show luminescence in the blue region of the spectrum, lifetimes between 0.6 and 2.1 μs, high quantum yield and good electrochemical behavior. The computational description (DFT) of the electronic structure highlights the key role of the conjugated π systems on optical and electrochemical properties of the final products.

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME NEW BENZTHIAZOLE OXIME ETHER DERIVATIVES

Some new oxime ether derivatives containing benzthiazole heterocyclic nuclei are synthesized. The reaction of 2-mercapto benzthiazole with α-halo ketones followed by reaction with hydroxylamine gave oxime derivatives which on reaction with alkyl halides viz. ethyl chloride, n-propyl chloride, and n-butyl chloride in absolute ethanol afforded the target compounds 4a-l. The structure of all the synthesized compounds was confirmed by spectroscopic methods like mass and NMR. All compounds after structural confirmation were tested for biological activities.

SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME NEW BENZTHIAZOLE OXIME ETHER DERIVATIVES

Some new oxime ether derivatives containing benzthiazole heterocyclic nuclei are synthesized. The reaction of 2-mercapto benzthiazole with α-halo ketones followed by reaction with hydroxylamine gave oxime derivatives which on reaction with alkyl halides viz. ethyl chloride, n-propyl chloride, and n-butyl chloride in absolute ethanol afforded the target compounds 4a-l. The structure of all the synthesized compounds was confirmed by spectroscopic methods like mass and NMR. All compounds after structural confirmation were tested for biological activities.

Synthesis of New 1-Aryl-2-(3,5-dimethylpyrazol-1-yl)ethanone Oxime Ether Derivatives and Investigation of Their Cytotoxic Effects

In this study, 12 new 1-aryl-2-(3,5-dimethylpyrazol-1-yl)ethanone oxime ether derivatives were designed and synthesized to investigate their cytotoxic effects. The in vitro cytotoxic activities of the compounds were evaluated against cervix, colon, breast, glioma, neuroblastoma, and lung cancer cell lines, as well as a healthy cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide (MTT) assays with 5-fluorouracil (5-FU) as the reference compound. Compound 5f (IC50 = 5.13 µM) was found to be more effective than 5-FU (IC50 = 8.34 µM) in the C6 cancer cell line, and it had no cytotoxic effect on the L929 healthy cell line. Flow cytometry was used to investigate the mechanism of action of compound 5f on the cell cycle of the C6 cell line. The analysis showed that cell death was significantly due to apoptosis. These results indicate that compound 5f induces cell cycle arrest, and may be effective in treating glioma.

Synthesis of Dithiacrown Ethers and Evaluation of Their Cytotoxic Activity

AbstractNew derivatives of thiacrown ethers were synthesized based on the domino reaction of 1,5‐bis(2‐formylphenthio)‐3‐oxapentane with ketones containing active methylene group and ammonium acetate. After 24 hours at moderate temperature, the reaction afforded new substances containing both polyether chain S(CH2)2−O−(CH2)2−S and heterocyclic piperidone. Particularly when benzyl acetoacetate was used, the three ‐ component reaction provided a final tetrahydropyridine derivative product containing enamine fragment instead of piperidone as expected. Physico‐chemical methods of analyses including IR, 1H &13C‐NMR and HRMS were used to clarify these structures. Subsequently, the cytotoxicity of five novel derivatives were evaluated on four cancer cells including HeLa (HeLa cervical cancer), Hep‐G2 (human hepatocellular carcinoma), MCF7 (human breast adenocarcinoma), Lu‐1 (human lung adenocarcinoma) and Vero cell. The result showed the potential application of these compounds in terms of biological activity.

Gold‐Catalyzed Intramolecular Tandem Cyclization of Alkynol‐Tethered Alkylidenecyclopropanes to Construct Naphthalene‐Fused Eight‐ to Eleven‐Membered Cyclic Ethers

AbstractA gold‐catalyzed intramolecular tandem cyclization of alkynol‐tethered alkylidenecyclopropanes was reported in this paper, providing a synthetic route to access naphthalene‐fused eight‐ to eleven‐membered cyclic ether derivatives in moderate to good yields. On the basis of control experiments and DFT calculations, a reasonable reaction mechanism involving a gold carbene intermediate was proposed, which was formed via the 6‐endo‐dig enyne cyclization process.magnified image

Juvenile hormone mimics with phenyl ether and amide functionality to be insect growth regulators (IGRs): synthesis, characterization, computational and biological study

A series of substituted phenyl ethers derivatives as juvenile hormone (JH) mimics (V1-V8) have been synthesized. Substituted phenoxyacetic acid and amino acid ethyl ester hydrochloride were prepared using NaOH, SOCl2. DCC method has been used for amide linkage. The structure of prepared compounds has been confirmed by Fourier Transform Infra-Red (FT-IR), Electrospray ionization-Mass spectrometry (ESI-MS), Proton and Carbon-13 nuclear magnetic resonance (1H-NMR, 13C-NMR) spectroscopic techniques. Biological efficacy of synthesized analogs has been carried out under laboratory conditions. Galleria mellonella (honey bee pest) has been chosen as testing insect. Juvenile hormone (JH) activity of synthesized compounds has been tested at different concentrations and compared with the standard juvenile hormone analogs (JHAs) pyriproxyfen (M1) and fenoxycarb (M2) against the fifth larval instar of G. mellonella. Compound ethyl 2-[2-(4-methylphenoxy)aminoacetyl]-3-phenyl-propanoate (V6) exhibited better activity among all the synthesized compounds (V1-V8) with LC50 and LC90 values of 0.11 mg/mL and 0.56 mg/mL respectively. Compounds showed insect growth regulating (IGR) activity at lower concentrations. In silico screening of all synthesized compounds with the W-cavity of juvenile hormone-binding protein (JHBP) of insect G. mellonella has been carried out. Chemical reactivity of synthesized series has been studied using DFT/B3LYP/6-311 + G(d,2p) method. Non-toxic behavior of molecules has also been observed from ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) study using discovery studio client 3.0. Communicated by Ramaswamy H. Sarma

Synergistic activation of photoswitchable supramolecular assembly based on sulfonated crown ether and dithienylethene derivative

Conformational regulation among two or more distant sites is not only one of the main pathways to accomplish multiple tasks in complex biological systems but also represents a powerful strategy to obtain stimuli-responsive supramolecular nanoconstructs with tailored physicochemical performance. We herein report the fabrication of a photochromic supramolecular assembly, which can be synergistically activated by the conformational regulation with bis(4,8-disulfonato-1,5-naphtho)-32-crown-8 and then reversibly switched by the through-space communication between restricted stilbazolium salt and photochromic dithienylethene. This work demonstrates that the synergistic conformational modulation via intra- and intermolecular interactions can be developed as a generalizable approach to construct more advanced biomimetic nanomaterials.

Synthesis of Oxidized 3β,3'β-Disteryl Ethers and Search after High-Temperature Treatment of Sterol-Rich Samples.

It was proven that sterols subjected to high-temperature treatment can be concatenated, which results in polymeric structures, e.g., 3β,3′β-disteryl ethers. However, it was also proven that due to increased temperature in oxygen-containing conditions, sterols can undergo various oxidation reactions. This study aimed to prove the existence and perform quantitative analysis of oxidized 3β,3′β-disteryl ethers, which could form during high-temperature treatment of sterol-rich samples. Samples were heated at 180, 200 and 220 °C for 0.5 to 4 h. Quantitative analyses of the oxidized 3β,3′β-disteryl ethers were performed with liquid extraction, solid-phase extraction and liquid chromatography coupled with mass spectrometry. Additionally, to perform this analysis, the appropriate standards of all oxidized 3β,3′β-disteryl ethers were prepared. Eighteen various oxidized 3β,3′β-disteryl ethers (derivatives of 3β,3′β-dicholesteryl ether, 3β,3′β-disitosteryl ether and 3β,3′β-distigmasteryl ether) were prepared. Additionally, the influence of metal compounds on the mechanism of ether formation at high temperatures was investigated.

Flavonoid Derivatives Targeting BCR-ABL Kinase: Semisynthesis, Molecular Dynamic Simulations and Enzymatic Inhibition.

Natural products have been universally approached in the research of novel trends useful to detail the essential paths of the life sciences and as a strategy for pharmacotherapeutics. This work focuses on further modification to the 6-hydroxy-flavanone building block aiming to obtain improved BCR-ABL kinase inhibitors. Ether derivatives were obtained from Williamson synthesis and triazole from Microwave- assisted click reaction. Chemical structures were finely characterized through IR, 1H and 13C NMR and HRMS. They were tested for their inhibitory activity against BCR-ABL kinase. Two inhibitors bearing a triazole ring as a pharmacophoric bridge demonstrated the strongest kinase inhibition at IC50 value of 364 nM (compound 3j) and 275 nM (compound 3k). 6-hydroxy-flavanone skeleton can be considered as a promising core for BCR-ABL kinase inhibitors.

A New Diphenyl Ether Derivative from a Mangrove Endophytic Fungus Phoma sp. L28

A New Diphenyl Ether Derivative from a Mangrove Endophytic Fungus Phoma sp. L28

Synthesis and antibacterial evaluation of (E)-1-(1H-indol-3-yl) ethanone O-benzyl oxime derivatives against MRSA and VRSA strains

Infections caused due to multidrug resistant organisms have emerged as a constant menace to human health. Even though numerous antibiotics are currently available for treating infectious diseases, a great number of bacterial strains have acquired resistance to many of them. Among these, infections caused due to Staphylococcus aureus are predominant in adult and paediatric population. Indole is a prominent chemical scaffold found in many pharmacologically active natural products and synthetic drugs. A number of oxime ether containing compounds have attracted attention of researchers owing to their interesting biological properties. Current work details the synthesis of indole containing oxime ether derivatives and their evaluation for antimicrobial activity against a panel of bacterial and mycobacterial strains. Synthesized compounds demonstrated good to moderate activity against drug-resistant S. aureus including resistant to vancomycin. Among all, compound 5h was found to possess potent activity against susceptible as well as MRSA and VRSA strains of S. aureus with MIC of 1 µg/mL and 2–4 µg/mL respectively. In addition, compound 5h was found to be non-toxic to Vero cells and exhibited good selectivity index of >40. Further, 5h, E-9a and E-9b possessed good biofilm inhibition against S. aureus. With these assuring biological properties, synthesized compounds could be potential prospective antimicrobial agents.

Catalytic Reductive Alcohol Etherifications with Carbonyl-Based Compounds or CO2 and Related Transformations for the Synthesis of Ether Derivatives.

Ether derivatives have myriad applications in several areas of chemical industry and academia. Hence, the development of more effective and sustainable protocols for their production is highly desired. Among the different methodologies reported for ether synthesis, catalytic reductive alcohol etherifications with carbonyl‐based moieties (aldehydes/ketones and carboxylic acid derivatives) have emerged in the last years as a potential tool. These processes constitute appealing routes for the selective production of both symmetrical and asymmetrical ethers (including O‐heterocycles) with an increased molecular complexity. Likewise, ester‐to‐ether catalytic reductions and hydrogenative alcohol etherifications with CO2 to dialkoxymethanes and other acetals, albeit in less extent, have undergone important advances, too. In this Review, an update of the recent progresses in the area of catalytic reductive alcohol etherifications using carbonyl‐based compounds and CO2 have been described with a special focus on organic synthetic applications and catalyst design. Complementarily, recent progress made in catalytic acetal/ketal‐to‐ether or ester‐to‐ether reductions and other related transformations have been also summarized.

Guanidinium-Responsive Crown Ether-Based Macrocyclic Amphiphile in Aqueous Medium.

Supramolecular assemblies based on oligo(ethylene glycol) (OEG) building blocks are well-known for their neutral chemical property and thermal-responsive behavior. Here, the cyclic "CLOSED" and linear "OPEN" typologies of OEGs led to dramatic difference in the sensitivity to guanidinium-containing species. From thermodynamic studies, the association constant (Ka) between the "CLOSED" form amphiphile and guanidinium salt was determined to be 28.7 M-1, whereas there was no detectable binding affinity for the "OPEN" form. Therefore, considering ion specificity, the present results establish that crown ether derivatives with "CLOSED" and "OPEN" topologies provide an easy-to-access model pair with designed ion-recognition sites and special functional moieties and geometries (like the binding pockets of enzymes or ion channels in cellular members) that allow the manipulation of the intercrossed relationship between supramolecular solutes, waters, and guanidinium salts. These supramolecular forces in aqueous solution offered an alternative strategy to fabricate thermal-responsive systems in ionic medium.

Dipodal Tetraamide Derivatives of 1,10-Diaza-18-Crown-6 and Alkylmalonic Acids-Synthesis and Use as Ionophores in Ion Selective Membrane Electrodes.

Novel dipodal derivatives of an 18-membered diaza-crown ether with two diamide chains featuring methylmalonic or butylmalonic acid residues were obtained and tested as ionophores in ion-selective plasticized membrane electrodes. The objective of the study was to identify measurement conditions which ensure the most favorable performance for magnesium ion-selective electrodes. The relationship between the molar lipophilic anion salt-to-ionophore ratio and selectivity of electrodes was examined. The best result was obtained for the conventional electrode containing Mg2 ionophore. Calculated selectivity coefficients were as follows: logKMg/Ca = −2.77, logKMg/Na = −3.46 and logKMg.K = −2.24 (SSM, 1M).

Construction of Cholesterol Oxime Ether Derivatives Containing Isoxazoline/Isoxazole Fragments and Their Agricultural Bioactive Properties/Control Efficiency.

To explore natural-product-based pesticidal candidates and high value-added application of cholesterol in agriculture, oximinoether derivatives of cholesterol-containing isoxazoline/isoxazole fragments (I-1∼I-16 and II-1∼II-18) were semiprepared by structural optimization of cholesterol. Their structures were characterized by optical rotation, high-resolution mass spectrometry (HRMS), IR, and 1H NMR spectroscopy. Particularly, the Z configurations of oxime fragments at the C-7 position of target compounds were undoubtedly determined by X-ray crystallography. Against Mythimna separata Walker, compounds 3e, I-8, I-14, and II-3 showed 2.4-2.7-fold growth inhibitory activity of the precursor cholesterol. Against Plutella xylostella Linnaeus, compounds I-6, I-7, and I-9 showed 2.4-2.7-fold oral toxicity of cholesterol. Against Aphis citricola Van der Goot, compounds 2e and II-15 exhibited 4.9 and 5.8-fold aphicidal activity of cholesterol, respectively. Notably, they showed good control effects (3.0-5.0-fold promising control efficiency of 1) against A. citricola in the greenhouse. Structure-activity relationships (SARs) suggested that the C-3 hydroxyl group and the C-7 position of cholesterol are two important modification sites. It will pave the way for future structural optimization and application of cholesterol derivatives as potential pesticidal agents in agriculture.

Synthesis, Characterization, Theoretical Analyses, and Investigation of Their Biological Activities of Acetovanillone-Derived Novel Benzyl Ethers

In this study, acetovanillone-derived novel benzyl ethers were synthesized as target compounds. For the synthesis of these target compounds, ketone derivatives (3a–b) were synthesized as the starting compounds. Compounds 4a–b, which are alcohol derivatives, were then synthesized from the reduction of these ketone derivatives. In the last stage of the synthesis study, benzyl ether derivatives (6a–h, 7a–h), the target compounds containing acetovanillone, were synthesized from the reaction of the alcohol derivatives (4a–b) with various benzyl halides (5a–h). The structures of the synthesized compounds were characterized by various spectroscopic methods (FT-IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis). In vitro antileishmanial and antibacterial activity tests were then performed for all synthesized compounds. Biological activity tests showed that while only a few of the compounds had antileishmanial activity, most had antibacterial activity. In addition, the ADME parameters, pharmacokinetic properties, and drug-like nature of all compounds were theoretically investigated using the SwissADME webserver. Finally, molecular docking simulations were carried out to support in vitro investigations and evaluate the inhibition effect of the synthesized compounds on the 3IW2 (Mycobacterium tuberculosis (Mtb) Cyp125; Pdb ID: 3IW2) receptor structure. Also, possible binding sites of some compounds with high affinity to Mtb Cyp125 according to docking results were identified.

Functionalized Cyclopentenones and an Oxime Ether as Antimicrobial Agents.

Several naturally occurring cyclopentenones, such as palmenones and nigrosporiones, exhibit antimicrobial activity. Herein we describe the antimicrobial activity of cyclopentenones and derivatives that can be easily accessed from biomass derivatives furfural and 5‐hydroxymethylfurfural. Upon screening a range of functionalized trans‐diamino‐cyclopentenones (DCPs) and δ‐lactone‐fused cyclopentenones (LCPs), an oxime ether derivative of DCP was identified that exhibited remarkable antimicrobial activity against Gram‐positive bacteria, including resistant strains such as methicillin‐resistant S. aureus (MRSA) and vancomycin‐resistant E. faecalis (VRE) strains.