Yunyun Zhou

Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position

In an attempt to search for potent insecticides targeting the ryanodine receptor (RyR), a series of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position were designed and synthesized. Their insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compound 6l and 6o showed 86% larvicidal activities against Plutella xylostella at the concentration of 0.1mg/L, while the activity of compound 6h against Mythimna separate was 80% at 1mg/L. The calcium imaging technique was applied to investigate the effects of some title compounds on the intracellular calcium ion concentration ([Ca(2+)](i)), experimental results demonstrated that compound 6h stimulates a transient elevation in [Ca(2+)](i) in the absence of external calcium after the central neurons dye loading with fluo-3 AM. However, when the central neurons were dyed with fluo-5N and incubated with 2-APB, [Ca(2+)]i decreased transiently by treated of compound 6h. All of the calcium imaging technique experiments demonstrated that these novel compounds deliver calcium from endoplasmic reticulum to cytoplasm, which proved that the title compounds were the possible activators of insect RyR.

Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing an amino acid methyl ester and their analogues.

On the basis of the commercial insecticide chlorantraniliprole, a series of novel N-pyridylpyrazolecarboxamides containing an amino acid methyl ester and their analogues were designed and synthesized. Their chemical structures were established on the basis of corresponding (1) H NMR spectroscopy, (13)C NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against oriental armyworm ( Mythimna separata ) and diamondback moth ( Plutella xylostella ) were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, of which the compounds 6 containing a methyl acrylate substructure had excellent larvicidal activity; for example, 6a displayed 100% larvicidal activity against P. xylostella at the concentration of 0.005 mg/L, whereas the activities of both compounds 6g and 6h against M. separata were 100% at 2.5 mg/L. The calcium imaging technique experiment results showed that novel compound 6 could elevate the calcium concentration in the cytoplasm. Furthermore, this study also provided evidence that compound 6h activates inositol 1,4,5-trisphosphate (IP3) sensitive intracellular calcium release channels in the endoplasmic reticulum of Spodoptera exigua third-instar larva neurons.

Synthesis and biological activities of 2,3-dihydro-1,3,4-oxadiazole compounds and its derivatives as potential activator of ryanodine receptors.

A series of novel 2,3-dihydro-1,3,4-oxadiazoles containing N-pyridylpyrazole carboxamides moieties were obtained by applying a new synthetic route. Their insecticidal tests against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to excellent activities at the testing concentrations. In particular, compound 6a showed 40% larvicidal activities against oriental armyworm at 1mg/L, while 7a against diamondback was 100% at 0.01mg/L. Calcium imaging results demonstrated that 6a, 6d and 7a stimulated a transient elevation in [Ca(2+)]i in the absence of external calcium after the central neurons dye loading with fluo-3 AM, implying that these novel compounds were potential activators of the ligand-gated calcium channel on the endoplasmic reticulum.

Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives targeting calcium channel.

A series of compounds containing dihydroquinazolinone moiety was designed and synthesized. Amine bridge part was changed in comparison with known anthranilic diamides insecticides. Their insecticidal activities against oriental armyworm (Mythimna separata) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compounds 5a and 5k showed 80% larvicidal activities against oriental armyworm at the concentration of 5mg/L. The present study also explored the possible effects of target compounds on the high voltage-gated calcium channel and the calcium channels in the endoplasmic reticulum in the central neurons isolated from the third instar larvae of Spodoptera exigua using whole-cell patch clamp and calcium imaging technique. The results showed that compound 5a activated the high voltage-gated calcium channel in the central neurons of S. exigua weakly. The peak currents only increased by 6% of the initial value at the end of the 10-min recording after treated with 0.22μM 5a, while chlorantraniliprole has an opposite effect. The effects of 5a on the intracellular calcium ion concentration ([Ca(2+)]i) in neurons were well investigated. The experimental results indicated that these novel compounds have different mechanism compared with chlorantraniliprole.

Synthesis and biological activity of novel 1-substituted phenyl-4-[N-[(2'-morpholinothoxy)phenyl]aminomethyl]-1H-1,2,3-triazoles.

In an attempt to search for potent antifungal agents, a series of novel 1‐substituted phenyl‐4‐[N‐[(2′‐morpholinothoxy)phenyl]aminomethyl]‐1H‐1,2,3‐triazoles 5a–m was designed and synthesized via Huisgen cycloaddition reaction between various (2‐morpholinoethoxy)‐N‐(prop‐2‐ynyl)aniline and different azidobenzene. Their chemical structures were characterized by 1H NMR and elemental analysis. A cleaner reaction with milder conditions and satisfactory yields was observed in the micorwave‐assisted synthesis of 4a–c. The fungicidal activity of some target compounds were evaluated in vitro against Fusarium omysporum, Physalospora piricola, Alternaria solani, Cercospora arachidicola and Gibberella zeae at 50 μg/mL. The bioassay results indicated that some compounds exhibited moderate fungicidal activities. Furthermore, compound 5h displayed equal activity to the positive control compounds against Alternaria solani.

Synthesis and biological activity of novel 1-substituted phenyl(glycosyl)-4-{4-[4,6-dimethoxy)pyrimidin-2-yl] piperazin-1-yl}methyl-1 H -1,2,3-triazoles

A series of novel 1-substituted phenyl or glycosyl 1,2,3-triazoles was designed and synthesized by azide-alkyne 1,3-dipolar cycloaddition between 4,6-dimethoxy-2-[4-prop-2-ynyl)piperazin-1-yl] pyrimidine and each of different azides catalysed by in situ generated Cu(I). The O-acyl protecting groups on glycosyl 1,2,3-triazoles were removed by triethylamine in wet methanol. Their chemical structures were established on the basis of corresponding 1H NMR, 13C NMR, MS and elemental analysis. The fungicidal activities of target compounds were evaluated in vitro against Fusarium omysporum, Physalospora piricola, Alternaria solani, Phytophthora capsici, Cercospora arachidicola and Gibberella zeae at 50 μg/mL. The bioassay results indicate that some of the compounds exhibited moderate but promising fungicidal activities. In particular, acetylated glucopyranosyl triazole displayed a good fungicidal activity against Physalospora piricola, which is equal to that of the positive control compound chlorothalonil.

Design, Synthesis and Insecticidal Activity of Novel Anthranilic Diamides Containing Oxime Ester and Diacylhydrazine Moieties

Two series of novel anthranilic diamides containing oxime ester and diacylhydrazine moieties were designed and synthesized. Their structures were characterized by melting points, 1H NMR, 13C NMR and high resolution mass spectrometry(HRMS). The single crystal structure of compound 7e was determined by X-ray diffraction and their evaluated insecticidal activity against oriental armyworm(Mythimna separata) indicates that some of the compounds exhibited moderate insecticidal activities. Among the 20 compounds, 6a and 6b show 100% larvicidal activity against Mythimna separate Walker at the test concentration of 100 mg/L.

Design, Synthesis and Structure-activity of N -Glycosyl-1-pyridyl-1 H -pyrazole-5-carboxamide as Inhibitors of Calcium Channels

Carbohydrates, with broad-spectrum structures and biological functions, are key organic compounds in nature, along with nucleic acids and proteins. As part of our ongoing efforts to develop a new class of pesticides with novel mechanism of action, a series of novel N-glycosyl-1-pyridyl-1H-pyrazole-5-carboxamide was designed and synthesized via the reactions of glycosyl methanamides and pyridyl-pyrazole acid. The compounds were characterized by 1H NMR and 13C NMR. The bioassay results indicate that some of these compounds exhibit moderate insecticidal activities and assessed as potential inhibitors of calcium channels. The modulation of voltage-gated calcium channels by compounds 4a and 5a in the central neurons isolated from the third instar larvae of Spodoptera exigua was studied by whole-cell patch-clamp technique. In addition, compound 5a inhibits the recorded calcium currents reversible on washout. Experimental results also indicate that compound 5a did not release stored calcium from the Endoplasmic Reticulum. The present work demonstrates that N-glycosyl-1-pyridyl-1H-pyrazole-5-carboxamides cannot be used as possible inhibitors of calcium channels for developing novel pesticides.

Regioselective Synthesis of Novel 3‐Thiazolidine Acetic Acid Derivatives from Glycosido Ureides

A series of 3‐thiazolidine acetic acid‐2‐(per‐O‐acetylglycosyl)‐1′‐imino‐α‐(substituted)‐4‐oxo ethyl ester derivatives (3a–t) were prepared via the reaction of substituted amino acid‐N‐[(per‐O‐acetylglycosylamino)thioxomethyl]‐ethyl ester with ethyl bromoacetate. The crystal structure of 3‐thiazolidine acetic acid‐2‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐d‐galactoyranosyl)‐1′‐imino‐α‐methyl‐4‐oxo ethyl ester 3g and 1H‐13C HMBC (2D NMR experiments) measurements of 3‐thiazolidine acetic acid‐2‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐d‐galactopyranosyl)‐1′‐imino‐α‐(1‐methylthio)ethyl‐4‐oxo ethyl ester 3j revealed the exclusive regioselectivity during the closure of these rings toward the N‐2 position of the thiourea moiety. Furthermore, the crystal structure of compound 3g showed that the attack of N‐1 was blocked by sugar ring owing to the steric effect. The bioactivity data suggested that compound 2e has mild anticancer activity.

Rational Design of a Green-Light-Mediated Unimolecular Platform for Fast Switchable Acidic Sensing

A controllable sensing ability strongly connects to complex and precise events in diagnosis and treatment. However, imposing visible light into the molecular-scale mediation of sensing processes is restricted by the lack of structural relevance. To address this critical challenge, we present the rational design, synthesis, and in vitro studies of a novel cyanostyryl-modified azulene system for green-light-mediated fast switchable acidic sensing. The advantageous features of the design include a highly efficient green-light-driven Z/E-isomerization (a quantum yield up to 61.3%) for fast erasing chromatic and luminescent expressions and a superior compatibility with control of ratiometric protonation. Significantly, these merits of the design enable the development of a microfluidic system to perform a green-light-mediated reusable sensing function toward a gastric acid analyte in a miniaturized platform. The results may provide new insights for building future integrated green materials.