Optimization, Structure-Activity Relationship, and Mode of Action of Nortopsentin Analogues Containing Thiazole and Oxazole Moieties.

Plant diseases seriously endanger plant health, and it is very difficult to control them. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities. Most of these compounds displayed higher antiviral activities than ribavirin. Compounds 1d, 1e, and 12a, with excellent antiviral activities, emerged as novel antiviral lead compounds, among which 1e was selected for further antiviral mechanism research. The mechanism research results indicated that these compounds may play an antiviral role by aggregating viral particles to prevent their movement in plants. Further fungicidal activity tests revealed that nortopsentin analogues displayed broad-spectrum fungicidal activities. Compounds 2p and 2f displayed higher antifungal activities against Alternaria solani than the commercial fungicides carbendazim and chlorothalonil. Current research has laid a foundation for the application of nortopsentin analogues in plant protection.

Synthesis, insecticidal activities and structure-activity relationship studies of novel anthranilic diamides containing pyridylpyrazole-4-carboxamide.

BACKGROUND: Anthranilic diamide insecticides containing pyridylpyrazole-5-carboxamide are extremely important in modern agriculture. New structurally modified compounds with high insecticidal activity were discovered by designing a series of novel pyridylpyrazole-4-carboxamides (9I to 9IV) and pyridylpyrazole-4-carboxamides (10I to 10IV), the latter designed by the cyclisation of two amides. The structure-activity relationship (SAR) between the two series is of interest. RESULTS: Two series of novel anthranilic diamides containing pyridylpyrazole-4-carboxamide were synthesised and characterised via melting point, (1)H NMR, (13)C NMR, MS and elemental analyses. The insecticidal activities of these compounds against Plutella xylostella were evaluated. At a concentration of 100 mg L(-1), the compounds with unmodified amide moieties (9I to 9IV) exhibited much better larvicidal activities than the other derivative compounds (10I to 10IV). Most of the compounds 9I to 9IV showed over 90% larvicidal activity at 100 mg L(-1). Furthermore, compounds 9IIIa, 9IIIc, 9IIId and 9IVd displayed significant insecticidal activity at 10 mg L(-1). Density functional theory (DFT) calculation was carried out to provide more information regarding SAR. CONCLUSION: Thirty-two new anthranlic diamides containing pyridylpyrazole-4-carboxamide were designed and obtained. SAR analysis and DFT calculation results revealed that the amide moiety had a very important effect on bioactivity. This work has provided information that could aid investigations of novel insecticides.

Synthesis, insecticidal activity, and structure-activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings.

A series of anthranilic diamides analogs (3­11, 16­24) containing 1,2,4- or 1,3,4-oxadiazole rings were synthesized and characterized by (1)H NMR, MS and elemental analyses. The structure of 3-bromo-N-(2-(3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (18, CCDC-) was determined by X-ray diffraction crystallography. The insecticidal activities against Plutella xylostella and Spodoptera exigua were evaluated. The results showed that most of title compounds displayed good larvicidal activities against P. xylostella, especially compound 3-bromo-N-(4-chloro-2-methyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (6), which displayed 71.43% activity against P. xylostella at 0.4 µg mL(-1) and 33.33% against S. exigua at 1 µg mL(-1). The structure-activity relationship showed that compounds decorated with a 1,3,4-oxadiazole were more potent than compounds decorated with a 1,2,4-oxadiazole, and different substituents attached to the oxadiazole ring also affected the insecticidal activity. This work provides some hints for further structure modification and the enhancement of insecticidal activity.

Design, synthesis, insecticidal activity and structure-activity relationship of 3,3-dichloro-2-propenyloxy-containing phthalic acid diamide structures.

BACKGROUND: Phthalic acid diamide derivatives are among the most important classes of synthetic insecticides. In this study, a 3,3-dichloro-2-propenyloxy group, the essential active group of pyridalyl derivatives, was incorporated into phthalic acid diamide derivatives with the aim of combining the active groups to generate more potent insecticides. RESULTS: Thirty-one new phthalic acid diamides were obtained, and these were characterised by (1) H and (13) C NMR. The structure of N(2) -[1,1-dimethyl-2-(methoxy)ethyl]-3-iodo-N(1) -[4-(3,3-dichloro-2-propenyloxy)-3-(trifluoromethyl)phenyl]-1,2-benzenedicarboxamide was determined by X-ray diffraction crystallography. The insecticidal activities of the compounds against Plutella xylostella were evaluated. The title compounds exhibited excellent larvicidal activities against P. xylostella. Structure-activity relationships revealed that varying the combination of aliphatic amide and aromatic amide moieties, or the nature and position of substituent Y on the aniline ring, could aid the design of structures with superior performance. CONCLUSION: A series of novel phthalic acid diamides containing a 3,3-dichloro-2-propenyloxy group at the 4-position of the aniline ring were designed and synthesised. Structure-activity relationships with the parent structure provided information that could direct further investigation on structure modification.

Soil microbial degradation of neonicotinoid insecticides imidacloprid, acetamiprid, thiacloprid and imidaclothiz and its effect on the persistence of bioefficacy against horsebean aphid Aphis craccivora Koch after soil application.

BACKGROUND: The neonicotinoids imidacloprid, imidaclothiz, acetamiprid and thiacloprid consist of similar structural substituents but differ considerably with respect to soil use. Therefore, the effects of soil microbial activity on the degradation and bioefficacy persistence of the four neonicotinoids were evaluated. RESULTS: In unsterilised soils, 94.0% of acetamiprid and 98.8% of thiacloprid were degraded within 15 days, while only 22.5% of imidacloprid and 25.1% of imidaclothiz were degraded over a longer period of 25 days. In contrast, in sterilised soils, the degradation rates of acetamiprid and thiacloprid were respectively only 21.4% and 27.6%, whereas the degradation rates of imidaclothiz and imidacloprid were respectively 9.0% and almost 0% within 25 days. The degradation products of imidacloprid and imidaclothiz were identified as olefin, nitroso or guanidine metabolites, the degradation product of thiacloprid was identified as an amide metabolite and no degradation product of acetamiprid was detected. A bioefficacy assay revealed that the bioefficacy and persistence of imidacloprid, imidaclothiz, acetamiprid and thiacloprid against horsebean aphid A. craccivora were related to their degradation rate and the bioefficacy of their degradation products in soil. CONCLUSION: Soil microbial activity played a key role in the bioefficacy persistence of neonicotinoid insecticides and therefore significantly affected their technical profile after soil application.

Synthesis, insecticidal activity, and structure-activity relationship of trifluoromethyl-containing phthalic acid diamide structures.

Phthalic acid diamides have received considerable interest in agricultural chemistry due to a novel action mode, extremely high activity against a broad spectrum of lepidopterous insects, low acute toxicity to mammals, and environmentally benign characteristics. A series of phthalic acid diamides (4I-4IV) with the CF3 group at meta position on the aniline ring were synthesized. Their structures were characterized by (1)H NMR and (13)C NMR (or elemental analysis). The structure of N(2)-[1,1-dimethyl-2-(methylthio)ethyl]-3-iodo-N(1)-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2-benzenedicarboxamide (4If) was determined by X-ray diffraction crystallography. Their insecticidal activities against Plutella xylostella were evaluated. The results show that some of the title compounds exhibit excellent larvicidal activities against P. xylostella, and improvement in larvicidal activity requires a reasonable combination of substituents in the parent structure, which provides some hints for further investigation on structure modification.

Biotransformation of thianicotinyl neonicotinoid insecticides: diverse molecular substituents response to metabolism by bacterium Stenotrophomonas maltophilia CGMCC 1.1788.

The carbon atom that neighbors the tertiary amine attached to the 6-chloro-3-pyridinylmethyl moiety is the key active site in the hydroxylation of the neonicotinoids imidacloprid and thiacloprid as well as in the demethylation of acetamiprid by Stenotrophomonas maltophilia CGMCC 1.1788. In this study, thianicotinyl neonicotinoid insecticides having diverse molecular substituents were biotransformed by S. maltophilia CGMCC 1.1788. The results indicated that the substitution of 6-chloropyridyl in imidacloprid with 2-chlorothiazol in imidaclothiz did not affect the hydroxylation of imidaclothiz and its hydroxylated site, while the oxadiazinane ring in thiamethoxam was not hydroxylated or opened. Moreover, the N-methyl group in clothianidin and thiamethoxam was not demethylated by S. maltophilia CGMCC 1.1788. The biotransformation of imidaclothiz was inhibited by piperonyl butoxide, implying that both hydroxylation and dehydrogenation are mediated by a P450 monooxygenase. The bioassay results suggested that the activity of 5-hydroxy and olefin imidaclothiz was similar but less than that of imidaclothiz against the horsebean aphid Aphis craccivora and mosquito larva Culex pipiens, while 5-hydroxy IMT showed weak activity against the brown planthopper Nilaparvata lugens.

Hydroxylation of thiacloprid by bacterium Stenotrophomonas maltophilia CGMCC1.1788.

Chloropyridinyl neonicotinoid insecticides play a major role in crop protection and flea control on cats and dogs. Imidacloprid, thiacloprid and acetamiprid have in common the 6-chloro-3-pyridinylmethyl group but differ in the nitroguanidine or cyanoamidine substituent on an acyclic or cyclic moiety. Our previous study found that Stenotrophomonas maltophilia CGMCC 1.1788 could hydroxylate imidacloprid to 5-hydroxy imidacloprid, and 5-hydroxy imidacloprid was easily converted to 10-19 times higher insecticidal olefin imidacloprid against aphid or whitefly. Acetamiprid could be transformed by S. maltophilia to form N-demethylation product(IM 2-1). In this paper, we examined S. maltophilia CGMCC 1.1788's ability of transformation of thiacloprid. S. maltophilia CGMCC 1.1788 can hydroxylate thiacloprid to 4-hydroxy thiacloprid characterized by HPLC-MS/MS and NMR analysis, however 4-hydroxy thiacloprid could not be converted to olefin thiacloprid under acid conditions like imidacloprid, whereas oxidized and decyonated simultaneously to form 4-ketone thiacloprid imine in alkaline solution. Bioassays indicated that 4-hydroxy thiacloprid had 156 times lower insecticidal activity than thiacloprid, and the ketone-imine derivative almost had no toxicity towards aphid. Though both imidacloprid and thiacloprid are hydroxylated by S. maltophilia CGMCC 1.1788 at the same carbon atom position, however the structural difference between in imidacloprid and thiacloprid, originate the entire discrepancy in bioefficacy of metabolite and its further degrading pathway. These results explain that why thiacloprid is classified as not relevant grade for soil and seed applications, whereas imidacloprid is recommended and acetamiprid is limited.

N-demethylation of neonicotinoid insecticide acetamiprid by bacterium Stenotrophomonas maltophilia CGMCC 1.1788.

Our previous study found that Stenotrophomonas maltophilia CGMCC 1.1788 could hydroxylate imidacloprid (IMI) to 5-hydroxy IMI. Here we first report that S. maltophilia CGMCC 1.1788 can demethylate acetamiprid (AAP) to form IM 2-1 that was characterized by HPLC-MS/MS and NMR. IM 2-1 retained only 10.5% contact activity and 13.1% oral activity of AAP against horsebean aphid. Time course of biotransformation under existing of sucrose revealed that 58.9% of AAP disappeared, but only 16.7% of reduced AAP was transformed to IM 2-1, after 8 days. Both demethylation and degradation of AAP contribute to the weak bioefficacy of AAP in soil application. The differences in metabolism and detoxification pathways between AAP and IMI are probably originated from the structural differences of these insecticides.

Microbial hydroxylation of imidacloprid for the synthesis of highly insecticidal olefin imidacloprid.

Microorganisms that bring about the aerobic transformation of imidacloprid (IMI) were isolated and screened, and the microbial regio- and stereoselective hydroxylation of IMI was studied. Some bacteria and fungi transformed IMI to 5-hydroxyl IMI. Bacterium Stenotrophomonas maltophilia CGMCC 1.1788 resting cells transformed IMI into R-5-hydroxyl IMI at the highest conversion rate. The enzyme catalyzed the stereoselective hydroxylation at position C12 of IMI in the imidazolidine ring. Under acidic conditions, 5-hydroxyl IMI was converted into olefin IMI in high molar conversion yield. The olefin IMI exhibited about 19 and 2.2 times more insecticidal efficacy than IMI against horsebean aphid imago and nymph, respectively, and about 1.4 times more active than IMI against brown planthopper imago. The transformation rate of IMI by resting cells of S. maltophilia CGMCC 1.1788 was promoted significantly by some carbohydrates and organic acids. The reaction medium with 5% sucrose resulted in 8.3 times greater biotransformation yield as compared with that without sucrose.