Synthesis and insecticidal activity of 6,8-dichloro-quinazoline derivatives containing a sulfide substructure

A series of 6,8-dichloro-quinazoline derivatives bearing a sulfide group was synthesized and characterized via ¹H NMR, ¹³C NMR, IR and elemental analyses. All the compounds were tested for their insecticidal activity against Plutella xylostella in vitro. The results indicate that the synthesized compounds possess good insecticidal activity. Among these compounds, Vc, Vi, Vj, Vk and Vm displayed 75 %, 85 %, 80 %, 70 % and 63 % activities, respectively. These may prove useful as insecticidal agents.     

Synthesis, crystal structure and biological activity of a novel anthranilic diamide insecticide containing allyl ether

In search of environmentally benign insecticides with high activity, low toxicity and low residue, a series of novel anthranilic diamides containing allyl ether were designed and synthesized. All the compounds were characterized by ¹H NMR spectroscopy, HRMS or elemental analysis. The single crystal structure of 18e was determined by X-ray diffraction. The insecticidal activities of the new compounds were evaluated. The results showed that some compounds exhibited excellent insecticidal activities against Lepidoptera pests. Among this series compounds, 18l showed 100 % larvicidal activity against Mythimna separate Walker and Plutella xylostella Linnaeus at the test concentration.     

Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery

Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL₁₀-b-PDMS₆₅-b-PVCL₁₀ vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg⁻¹ single dose) of PVCL₁₀-PDMS₆₅-PVCL₁₀ vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research.     

Stoffwechselprodukte von Mikroorganismen. 231. Mitteilung. Bafilomycin-A1-21-O-(α-L-rhamnopyranosid): Strukturaufklärung durch chemische Verknüpfung mit Bafilomycin A1 und Leucanicidin

Isolation of Bafilomycin-A₁-21-O-(α-L-rhamnopyranoside). Structural Determination by Chemical Correlation with Bafilomycin A₁ and Leucanicidin From cultures of an actinomycete strain, the known antifungal and insecticidal antibiotic leucanicidin ( 1 ) and a hitherto unknown antifungal antibiotic, bafilomycin-A₁-21-O-(α-L-rhamnopyranoside) ( 2 ), were isolated. The latter is spectroscopically closely related to 1 and bafilomycin A₁ ( 3 ) and gave degradation products identical with compounds obtained by analogous degradation of 1 and 3 .     

Determination of antifouling pesticides and their degradation products in marine sediments by means of ultrasonic extraction and HPLC–APCI–MS

A method has been developed for the simultaneous determination of antifouling pesticides and some of their degradation products, e.g. dichlofluanid, diuron, demethyldiuron, 1-(3,4-dichlorophenyl)urea, sea-nine, Irgarol 1051 and one of its metabolites (2-methylthio-4-tert-butylamino-s-triazine) in marine sediments. The determination of these compounds in sediment samples was performed by means of methanolic ultrasonic extraction then clean-up on an Isolute ENV+ solid phase extraction (SPE) cartridge. The resulting extract was then analyzed by reversed-phase high-performance liquid chromatography coupled with atmospheric-pressure chemical-ionization mass spectrometry in negative and positive ion modes (HPLC–APCI–MS). Recovery ranged from 54–109% for the antifouling agents and their degradation products. The determination limits for the different compounds varied between 0.2 and 1.6 μg kg^–1 dry sediment. The analytical procedure was successfully applied to the determination of these pesticides and their degradation products in marine sediment samples from different marinas of the Catalan coast. The compounds detected were: diuron, dichlofluanid, demethyldiuron, sea-nine, and Irgarol 1051. The highest concentrations were those of diuron and Irgarol 1051 – 136 and 88 μg kg^–1, respectively.     

Determination of the configuration in six-membered saturated heterocycles (N,P, S,Se) and their oxidation products using experimental and calculated NMR chemical shifts

The six-membered saturated heterocycles—4-tert-butyl-1-methylpiperidine, 4-tert-butyl-1-methylphosphine, 4-tert-butyl-tetrahydro-2H-thiopyran, and 4-tert-butyl-tetrahydro-2H-selenopyran—were prepared as suitable model compounds with well-defined geometry for an NMR study of their oxidation products. The corresponding epimeric N-oxides, phosphinoxides, sulfoxides, and selenoxides were obtained by standard chemical preparation and also by in situ oxidation with meta-chloroperbenzoic acid directly in the NMR tube. The experimental ¹H and ¹³C chemical shifts were compared with corresponding calculated data obtained by GIAO approach with DFT, MP2, and HF methods and various basis sets. The correlation of experimental versus calculated data showed the possibility to determine the stereochemistry of the epimeric oxidation products using fast DFT B3LYP/6-31G* method for both geometry optimization and NMR chemical shifts calculation.     

Structure-Based Bioisosterism Design,Synthesis, Biological Activity and Toxicity of 1,2,4-Oxadiazole Substituted Benzamides Analogues Containing Pyrazole Rings

In order to discover pesticidal lead compounds with high activity and low toxicity, a series of novel benzamides substituted with pyrazole-linked 1,2,4-oxadiazole were designed via bioisosterism. The chemical structures of the target compounds were confirmed via ¹H NMR, ¹³C NMR and HRMS analysis. The preliminary bioassay showed that most compounds exhibited good lethal activities against Mythimna separate, Helicoverpa armigera, Ostrinia nubilalis and Spodoptera frugiperda at 500 mg/L. Particularly in the case of Mythimna separate, compound 14q (70%) exhibited obvious insecticidal activity. In addition, compound 14h demonstrated good fungicidal activity against Pyricularia oryae with an inhibition rate of 77.8%, and compounds 14e, 14k, 14n and 14r also showed certain antifungal activities (55.6–66.7%). The zebrafish toxicity test showed that the LC₅₀ of compound 14h was 14.01 mg/L, which indicated that it may be used as a potential leading compound for further structural optimization.     

Synthesis and chromatographic study of methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d-ribofuranoside

The synthesis of two riboside-containing arsenic compounds, methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d- ribofuranoside is presented in this paper. Intermediates and final products of the synthesis were examined by gas chromatography and thin layer chromatography. The purity of the products was assessed by NMR spectroscopy. Trimethylsilylation was used to volatilise sugar compounds and thus use of the costly HPLC–MS technique was avoided. The results affirmed the presence of tautomers in case of arsenosugars.     

Chemical Hemisynthesis of Sulfated Cyanidin-3-O-Glucoside and Cyanidin Metabolites

The metabolism of anthocyanins in humans is still not fully understood, which is partly due to the lack of reference compounds. It is known that sulfation is one way of the complex phase II biotransformation mechanism. Therefore, cyanidin-3-O-glucoside and the cyanidin aglycone were chemically converted to their sulfates by reaction with sulfur trioxide-N-triethylamine complex in dimethylformamide. The reaction products were characterized by UHPLC coupled to linear ion trap and IMS-QTOF mass spectrometry. Based on MS data, retention times, and UV-Vis spectra, the compounds could tentatively be assigned to A-, C-, or B-ring sulfates. Analysis of urine samples from two volunteers after ingestion of commercial blackberry nectar demonstrated the presence of two sulfated derivatives of the cyanidin aglycone and one sulfated derivative of the cyanidin-3-O-glucoside. It was found that both the A ring and the B ring are sulfated by human enzymes. This study marks an important step toward a better understanding of anthocyanin metabolism.     

Gas chromatographic-mass spectrometric determination of phenols and heterocyclic nitrogen compounds in the thermal degradation products of epoxy powder paint

The thermal decomposition of an amine-cured epoxy powder paint with a sample size permitting secondary reactions was studied. The decomposition was carriedout at 350°C in synthetic air. Components of interest were extracted from the complex matrix of degradation products and concentrated, after which identification was performed by gas chromatography-mass spectrometry.The study showed that the pyrolysis matrix can be fractionated on the basis of the chemical nature of its components. Sixteen nitrogen-containing heterocyclic compounds and ten different phenols were identified.     

Gas chromatographic-mass spectrometric characterisation of amiton and the recovery of amiton from concrete,paint, rubber and soil matrices

Amiton [O,O-diethyl S-[2-(diethylamino)ethyl] phosphorothiolate], is an organophosphorus chemical included in Schedule 2 of the Chemical Weapons Convention (CWC). Verification provisions under the CWC rely on the existence of a database of analytical information for scheduled chemicals and related compounds. Little analytical information is available for amiton. In this study, gas chromatography-mass spectrometry (GC-MS) characterisation of amiton and its typical impurities (including by-products and degradation products), supported by selective GC detection and 31P NMR data, was undertaken. Twenty-one compounds, including a by-product unique to amiton from an industrial source, were identified. Involatile degradation products of amiton were derivatised to enable their identification by GC-MS. The recovery of amiton from matrices that may be expected in an inspection scenario (i.e. concrete, paint, rubber and soil) was also examined. Paint and concrete matrices were the most useful matrices for the detection of amiton, and its by-products and degradation products. Amiton was readily detected in these matrices after 28 days.     

QSAR for Acetylcholinesterase Inhibition and Toxicity of Two Classes of Phosphoramidothioates

Abstract

Methamidophos (Met) is a weak inhibitor of housefly head AChE but at the same time it is highly toxic to the common housefly. The lethality of Met is believed to be due to AChE inhibition. An extensive QSAR study may help in determining the mode of action of Met in vivo and in vitro and provide a rational for its high insecticidal toxicity. Acephate (Ace), like Met, is a poor inhibitor of AChE in vitro and has a comparable to Met insect toxicity in vivo. Contrary to Met, though, Ace has much lower mammalian toxicity. Understanding the structural properties which make insecticides toxic to insects but not to mammals is of great importance, since mammals (including humans) are inadvertently exposed to these compounds.

Our results were consistent with the model in which both the in vitro and in vivo toxicity of Met depends on the inhibition of the active center of AChE by the unchanged Met. An optimal susceptibility to hydrolysis is needed for Met and its analogs to have high insecticidal activity since in order to phosphorylate AChE they need to be hydrolyzed and at the same time their stability is of great importance in vivo for accumulating at the site of action. The insecticidal activity of Ace analogs may be due to direct interaction with the active center of the AChE. The mammalian toxicity of Ace analogs may be due to interaction with an 'allosteric' reaction center in the AChE.     

Synthesis,Characterization, and Biological Evaluation of Some Novel Pyrazolo[5,1-b]thiazole Derivatives as Potential Antimicrobial and Anticancer Agents

The pharmacological activities of thiazole and pyrazole moieties as antimicrobial and anticancer agents have been thoroughly described in many literature reviews. In this study, a convenient synthesis of novel pyrazolo[5,1-b]thiazole-based heterocycles was carried out. The synthesized compounds were characterized by IR, ¹H and ¹³C NMR spectroscopy and mass spectrometry. Some selected examples were screened and evaluated for their antimicrobial and anticancer activities and showed promising results. These products could serve as leading compounds in the future design of new drug molecules.     

α-aminoazoles in synthesis of heterocycles: III. 4-trifluoromethylpyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridines: Synthesis and structure

Cyclocondensation of N-substituted 5-aminopyrazoles with fluorinated 1,3-diketones yielded 4-trifluoromethyl-substituted pyrazolo[3,4-b]pyridines as the only reaction products. The regiostructure of compounds obtained was proved by ¹H and ¹³C NMR homo- and heteronuclear correlation spectroscopy. Characteristic chemical shifts in the ¹³C NMR spectra of regioisomeric pyrazolo[3,4-b]pyridines were established.     

Synthesis,Crystal Structure,and Biological Activity of Novel Anthranilic Diamide Insecticide Containing Propargyl Ether Group

In search of environmentally benign insecticides with high activity, low toxicity, and low residue, a series of novel anthranilic diamide containing propargyl ether were designed and synthesized. All compounds were characterized by ¹H NMR spectroscopy, high‐resolution mass spectrometry, or elemental analysis. The single crystal structure of 18g was determined by X‐ray diffraction. The insecticidal activities against Lepidoptera pests of the new compounds were evaluated. Their insecticidal activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the tested concentration.     

Study of the forced degradation behavior of prasugrel hydrochloride by liquid chromatography with mass spectrometry and liquid chromatography with NMR detection and prediction of the toxicity of the characterized degradation products

Prasugrel was subjected to forced degradation studies under conditions of hydrolysis (acid, base, and neutral), photolysis, oxidation, and thermal stress. The drug showed liability in hydrolytic as well as oxidative conditions, resulting in a total of four degradation products. In order to characterize the latter, initially mass fragmentation pathway of the drug was established with the help of mass spectrometry/time‐of‐flight, multiple stage mass spectrometry and hydrogen/deuterium exchange data. The degradation products were then separated on a C₁₈ column using a stability‐indicating volatile buffer method, which was later extended to liquid chromatography‐mass spectrometry studies. The latter highlighted that three degradation products had the same molecular mass, while one was different. To characterize all, their mass fragmentation pathways were established in the same manner as the drug. Subsequently, liquid chromatography‐nuclear magnetic resonance (NMR) spectroscopy data were collected. Proton and correlation liquid chromatography with NMR spectroscopy studies highlighted existence of diastereomeric behavior in one pair of degradation products. Lastly, toxicity prediction by computer‐assisted technology (TOPKAT) and deductive estimation of risk from existing knowledge (DEREK) software were employed to assess in silico toxicity of the characterized degradation products.     

Combination of preparative HPLC and HSCCC methods to separate phosphodiesterase inhibitors from Eucommia ulmoides bark guided by ultrafiltration-based ligand screening

Phosphodiesterase (PDE) inhibitors are widely used because of their various pharmacological properties, and natural products are considered the most productive source of PDE inhibitors. In this work, a new ultrafiltration–high-performance liquid chromatography (HPLC)–diode-array detection–mass spectrometry based ligand screening was developed for the first screening of PDE inhibitors from Eucommia ulmoides bark, and then the target bioactive compounds were prepared by combination of stepwise preparative HPLC and high-speed countercurrent chromatography (HSCCC) methods. Experiments were conducted to optimize the parameters in ultrafiltration, stepwise preparative HPLC, and HSCCC to allow rapid and effective screening and isolation of active compounds from complex mixtures. Seven lignans with purity over 97 % were isolated and identified by their UV, electrospray ionization mass spectrometry, and NMR data as (+)-pinoresinol-4,4′-di-O-β-D-glucopyranoside (1), (+)-pinoresinol-4-O-β-D-glucopyranosyl(1?→?6)-β-D-glucopyranoside (2), (+)-medioresinol-4,4′-di-O-β-D-glucopyranoside (3), (+)-syringaresinol-4,4′-di-O- β-D-glucopyranoside (4), (?)-olivil-4′-O-β-D-glucopyranoside (5), (?)-olivil-4-O-β-D- glucopyranoside (6), and (+)-pinoresinol-4-O-β-D-glucopyranoside (7). Compound 2 was first isolated from the genus Eucommia. Lignan diglucopyranosides (compounds 1–4) shower a greater inhibitory effect than lignan monoglucopyranosides (compounds 5–7). The method developed could be widely applied for high-throughput screening and preparative isolation of PDE inhibitors from natural products.     

Syntheses of 4-methoxymethylbenzyl permethrinates containing fluorine and their insecticidal activity

In order to investigate the relationship between the position of fluorine atom and insecticidal activity about 4-methoxymethylbenzyl permethrinates containing fluorine, 2 and 3-fluoro-4-methoxymethylbenzyl (±)-cis-permethrinate were synthesized. Their insecticidal activities were tested and the fluorine effect of title compounds was discussed.     

Synthesis,insecticidal activities,and SAR studies of novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives

Diamide compounds such as chlorantraniliprole, a famous anthranilic diamide insecticide targeting the insect ryanodine receptor (RyR), have received continuous attention in pesticide research during the past 15 years owing to their excellent insecticidal potentials. With the aim of discovering new heterocyclic pesticides used for crop protection, based on the structural information of compound M from the reported pharmacophore-based virtual screening for RyR insecticides and diamide compound, a series of new heterocyclic mono-, di-, and tri-amide derivatives containing piperazine moiety have been synthesized in this paper. The new compounds were identified and confirmed by melting point, ¹H NMR, ¹³C NMR and HRMS. Compound M was firstly validated for insecticidal activities, and the new synthesized compounds were all made comprehensive insecticidal evaluations against diamondback moth and oriental armyworm. The bioassay results showed that some of the compounds exhibit favorable insecticidal potentials, particularly some novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives such as 8g, 14a, 15a, 15g, 15i, 15j, 15k, 15l, and 15m could be used as new insecticidal leading structures for further study (e.g., towards diamondback moth, 15i-15m LC₅₀: 0.0022−0.0081 mg/L). The structure-activity relationships of the compounds discussed in detail provide useful guidance for further design and development of new insecticides.     

含噻唑和1,2,3-三唑环的硫代磷酸肟酯的合成与生物活性

为了寻找高效、低毒的新型农用化学品,以2-氯-5-(氯甲基)噻唑为起始原料,设计合成了一系列新型含1,2,3-三唑和噻唑杂环的肟醚硫代磷酸酯衍生物,采用IR, 1H NMR, 31P NMR, MS和元素分析对其进行了结构表征。初步生物活性测试结果表明：该系列化合物具有中等程度的杀虫和杀菌活性。