Lixia Xiong

Synthesis and Insecticidal Activities of Novel Anthranilic Diamides Containing Modified N-Pyridylpyrazoles

In order to look for novel insecticides targeting the ryanodine receptor, four new series of anthranilic diamides containing modified N-pyridylpyrazoles were designed and synthesized. All of the compounds were characterized and confirmed by (1)H NMR, (13)C NMR, and HRMS. The single crystal structure of 10c was determined by X-ray diffraction. 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, while compound 19 showed comparable higher activity at the concentration of 0.125 mg/L. The preliminary structure-activity relationship (SAR) was discussed.

Design, synthesis and insecticidal activity of novel phenylpyrazoles containing a 2,2,2-trichloro-1-alkoxyethyl moiety.

A series of novel phenylpyrazoles containing a 2,2,2-trichloro-1-alkoxyethyl moiety were designed and synthesized via the key intermediate 5-trichloroethylideneimino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-alkylsulfenylpyrazole (5). The addition reaction of the imine 5 was closely related with the nature of the alcohol. The target compounds were confirmed by (1)H NMR and elemental analysis. The results of bioassays indicated that the target compounds possessed excellent activities against a broad spectrum of insects such as bean aphid (Aphis craccivora), mosquito (Culex pipiens pallens) and diamondback moth (Plutella xylostella). Especially, the foliar contact activity against bean aphid of compound 7h at 2.5 mg kg(-1) was 89%, the larvacidal activity against mosquito of compound 6c at 2.5 microg kg(-1) was 100%, the activity against diamondback moth of compound 7a at 5 mg kg(-1) was 87%, and all of these activities were much higher than the contrast ethiprole. The results of insecticidal activities showed that the two pairs of enantiomers 7d-1 and 7d-2 gave activities without distinctive difference, and it was the similar situation for 7e-1 and 7e-2. Interestingly, the target compounds exhibited high selectivity between diamondback moth and oriental armyworm, both of which are of the order Lepidoptera. The 2,2,2-trichloro-1-alkoxyethyl moiety was essential for high insecticidal activities.

Synthesis and Insecticidal Activities of Novel Anthranilic Diamides Containing Acylthiourea and Acylurea

Two series of anthranilic diamides containing acylthiourea and acylurea linkers were designed and synthesized, with changed length and flexibility of the linkers to compare to known anthranilic diamide insecticides. In total, 26 novel compounds were synthesized, and all compounds were characterized by (1)H nuclear magnetic resonance and high-resolution mass spectrometry. Their insecticidal activities against oriental armyworm (Mythimna separata), mosquito larvae (Culex pipiens pallens), and diamondback moth (Plutella xylostella) were evaluated. The larvicidal activities against oriental armyworm indicated that the introduction of acylthiourea into some structures could retain their insecticidal activity; 8 of the 15 compounds (13a-13e, 14a-14e, and 15a-15e) exhibited 100% larvicidal activity at 10 mg/L. However, the introduction of acylurea decreased the insecticidal activity; only 3 of the 11 compounds (17a-17k) exhibited 100% larvicidal activity at 200 mg/L. The whole-cell patch-clamp technique indicated that compound 13b and chlorantraniliprole exhibited similar effects on the voltage-gated calcium channel. The calcium-imaging technique was also applied to investigate the effects of compounds 13b and 15a on the intracellular calcium ion concentration ([Ca(2+)](i)), which indicated that they released stored calcium ions from endoplasmic reticulum. Experimental results denoted that several new compounds are potential activators of the insect ryanodine receptor (RyR).

Design, synthesis, and insecticidal activity of novel pyrazole derivatives containing α-hydroxymethyl-N-benzyl carboxamide, α-chloromethyl-N-benzyl carboxamide, and 4,5-dihydrooxazole moieties.

On the basis of commercial insecticides tebufenpyrad and tolfenpyrad, two series of novel pyrazole-5-carboxamides containing α-hydroxymethyl-N-benzyl or α-chloromethyl-N-benzyl and pyrazoles containing 4,5-dihydrooxazole moieties were designed and synthesized via the key intermediate 2-amino-1-(4-substituted) phenyl ethanol. The structures of target compounds were confirmed by (1)H NMR and elemental analysis or high-resolution mass spectrum (HRMS), and their activities against cotton bollworm (Helicoverpa armigera), diamondback moth (Plutella xylostella), bean aphid (Aphis craccivora), mosquito (Culex pipiens pallens), and spider mite (Tetranychus cinnabarinus) were tested. The results of bioassays indicated that compounds containing α-chloromethyl-N-benzyl and compounds containing 4,5-dihydrooxazole showed high insecticidal activity against cotton bollworm. Especially, stomach activities of compounds Ij, Il, and IIe were 60% at 5 mg kg(-1). Moreover, the target compounds exhibited high selectivity between cotton bollworm and diamondback moth, although both of them belong to the order Lepidoptera. Although the activities against diamondback moth were at a low level, some of the target compounds exhibited antifeedant activity. The compounds also had good activities against bean aphid, mosquito, and spider mite. The foliar contact activity of compounds Ic, Id, Ie, and IIf against bean aphid were 95, 95, 100, and 95%, respectively, at 200 mg kg(-1). The miticidal and ovicidal activities of compound IIi against spider mite were both 95% at 200 mg kg(-1). Furthermore, a trivial change at 4-position of pyrazole ring would lead to great changes in properties and activities, which can easily be deduced by comparing the activities of compounds in series I (4-chloro-pyrazole compounds) with corresponding compounds in series II (4-hydro-pyrazole compounds), especially from the miticidal and ovicidal activities of Ii and IIi against spider mite.

Synthesis, insecticidal activities, and SAR studies of novel pyridylpyrazole acid derivatives based on amide bridge modification of anthranilic diamide insecticides.

Anthranilic diamides are one of the most important classes of modern agricultural insecticides. To discover new structure-modified compounds with high activity, series of novel carbonyl thioureas, carbonyl ureas, oxadiazoles, carbonyl thiophosphorylureas, oxadiazole-containing amides, and thiazoline-containing amides were designed through the modification of the amide bridge based on the structure of chlorantraniliprole and were synthesized, and bioassays were carried out. The compounds were characterized and confirmed by melting point, IR, (1)H NMR, and elemental analyses or HRMS. Preliminary bioassays indicated that some compounds exhibited significant insecticidal activities against oriental armyworm, diamondback moth, beet armyworm, corn borer, and mosquito. Among them, trifluoroethoxyl-containing carbonyl thiourea 20a showed best larvicidal activity against oriental armyworm, with LC50 and LC95 values of 0.1812 and 0.7767 mg/L, respectively. Meanwhile, 20c and 20e showed 86 and 57% death rates against diamondback moth at 0.005 mg/L, and the LC50 values of the two compounds were 0.0017 and 0.0023 mg/L, respectively, which were lower than that of the control chlorantraniliprole. The relationship between structure and insecticidal activity was discussed, and the HF calculation results indicated that the carbonyl thiourea moiety plays an important role in the insecticidal activity. The present work demonstrated that the trifluoroethoxyl-containing carbonyl thioureas can be used as lead compounds for further development of novel insecticides.

Design, Synthesis, and Insecticidal Evaluation of New Benzoylureas Containing Isoxazoline and Isoxazole Group

Twenty-two new benzoylphenylureas containing isoxazoline and the isoxazole group were designed and synthesized, and their structures were characterized by (1)H NMR and elemental analysis (or HRMS). The larvicidal activities against Oriental armyworm, mosquito, and diamondback moth of the new compounds were evaluated. Compounds I-1 and III-1 showed nearly the same level of insecticidal activity against Oriental armyworm as commercial insecticide Flucycloxuron and surprisingly exhibited much higher larvicidal activities against diamondback moth than Flucycloxuron.

Synthesis, larvicidal activity, and SAR studies of new benzoylphenylureas containing oxime ether and oxime ester group

A series of new structural benzoylphenylureas (BPUs) containing oxime ether and oxime ester group were designed and synthesized. The larvicidal activities against Oriental armyworm and mosquito of these benzoylphenylureas were evaluated and the result of bioassay displayed specific structure-activity relationship (SAR). Most of the compounds exhibited excellent larvicidal activities against Oriental armyworm and mosquito. Interestingly, some compounds showed different structure-activity relationship towards diamondback moth, beet armyworm, and corn borer although three tested insects all belong to the same insect order.

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.

Design, synthesis, and insecticidal evaluation of new pyrazole derivatives containing imine, oxime ether, oxime ester, and dihydroisoxazoline groups based on the inhibitor binding pocket of respiratory complex I.

On the basis of complex I receptor protein binding site and commercial tebufenpyrad and tolfenpyrad, four series of novel pyrazole-5-carboxamides containing imine, oxime ether, oxime ester, and dihydroisoxazoline were designed and synthesized via the key intermediate 4-chloro-3-ethyl-N-(4-formylbenzyl)-1-methyl-1H-pyrazole-5-carboxamide. The structures of target compounds were confirmed by ¹H NMR and high-resolution mass spectrum (HRMS). The results of bioassays indicated that the target compounds possessed good-to-excellent activities against a broad spectrum of insects such as cotton bollworm (Helicoverpa armigera), spider mite (Tetranychus cinnabarinus), bean aphid (Aphis craccivora), and mosquito (Culex pipiens pallens), but gave different structure-activity relationships for each species. Compounds containing imine showed high insecticidal activity against cotton bollworm. Especially, stomach activity of compounds 5-1c was 60% at 11 mg kg⁻¹. The compounds also had good activities against bean aphid and mosquito. The foliar contact activity of compounds 5-1a, 5-1b, 5-1e, 5-3c, and 5-3d against bean aphid were 90, 100, 90, 90, and 90%, respectively, at 200 mg kg⁻¹. The activity of compound containing dihydroisoxazoline moiety (5-4) against mosquito was 60% at 1 mg kg⁻¹, which was near that of tebufenpyrad. The introduction of dihydroisoxazoline structure (5-4) was advantageous to improve the activity of the compound against adult mites compared with other structures; the miticidal activity of 5-4- against adult mites was 60% at 50 mg kg⁻¹.

Modulations of high-voltage activated Ca2+ channels in the central neurones of Spodoptera exigua by chlorantraniliprole

The modulation of voltage‐gated calcium channels by chlorantraniliprole in the central neurones isolated from third‐instar larvae of Spodoptera exigua is studied by the whole‐cell patch‐clamp technique. The current of calcium in the third‐instar larvae of S. exigua is identified as a high‐voltage activated Ca2+ current. During the 10‐min recording, the current–voltage relationship curves of whole‐cell calcium channels are shifted in a negative direction by 10 mV compared with the control group. The fact that the gravity rundown of calcium current in the treated group is more apparent than in the control group demonstrates that the open channels are constantly inactivated. In addition, chlorantraniliprole inhibits the recorded calcium currents in a concentration‐dependent manner, which is irreversible on washout.