Synthesis,Bioactivity And3D-QSAR Of The Novel Strobilurins Containing Hydrocarbylidenehydrazinecarboximidamide

Strobilurin fungicides possess several advantages such as low toxicity, high efficiency,broad-spectr-um, systemic, but its single-action site and prominent resistance problems after frequently used in field-s limit its widespread application. Thus, it is essential to explore novel strobilurin fungicides with multi-sites of action and new structure.On the basis of the preliminary work, we found hydrocarbylidene hydrazinecarboximidamide was a highly active unit extracted from neonicotinoids and hydrocarbylidene hydrazinecarboxamides belong to two different typical insecticides,. We combined it with key intermediates (E)-2-(2-bromomethyl) phenyl-2-methoxyimino acetate and (E)-2-(2-bromomethyl) phenyl-3-methoxypropenoate of stro-bilurin fungicides, and synthesized seventy novel strobilurins containing hydrocarbylidene hydrazinec-arboximidamide (see figure below), isolated three kinds of byproducts at the same time and discussed its formation mechanism. We initially explored the cyclization reaction conditions of target compound under acetic acid and obtained one3-nitroimine-1,2,4-triazoline derivatives. All compounds were char-acterized by1H NMR, IR and HRMS.The activities of the target compounds against Myzus persicae Sulzer, Hyalopterus amygdali Blanchard and Aphis glycines Matsmura were screened by the method of immersion, spraying and dry film. As shown by the insecticidal activity data against Myzus persicae Sulzer, the LC50value of most compounds were less than30ug/mL, especially compound ZNQ-1420,ZNQ-1426and ZNQ-1448,the LC50value were0.53,0.32and0.19μg/mL, respectively; the activity against Hyalopterus amygdali Blanchard showed that the LC50value of most compounds were less than50ug/mL; in particular ZNQ-1404, ZNQ-1407and ZNQ-1443with a LC50value3.00,1.40and2.02μg/mL, respectively; the initial insecticidal activity against Aphis glycines Matsmura indicated that the lethal rate of ZNQ-1455, ZNQ-1456, ZNQ-1462, ZNQ-1463, ZNQ-1464and ZNQ-1466were exceeded70%at the concentration of200ug/mL, compound ZNQ-1463even reached92%.Preliminary bioassay of part compouds was completed against Rhizoctonia solani, Phytophthora infestans, phytophthora capsici, Physalospora piricoia, Colletotrichum lagenarium, Pythium aphanide-rmatum and Botrytis cinerea. Overall these compounds displayed good fungicidal activity against Bot-rytis cinerea, better than Physalospora piricola, Rhizoctonia solani and Pythium aphanidermatum, but bad effective to phytophthora capsici and Colletotrichum lagenarium. Among them, compound ZNQ-14 59has good fungicidal activity against Botrytis cinerea with an inhibition rate of77.4%. The inhibition rate of ZNQ-1401and ZNQ-1405against Physalospora piricola were74.3%and70.7%, respectively, The inhibition rate of ZNQ-1411and ZNQ-1426was60.1%against Phytophthora infestan-s.ZNQ-1454have good fungicidal activity against Rhizoctonia solani with an inhibition rate of41.7%. They all showed better or comprable activity than Azoxystrobin. It is also worth to mention that the activity of the by-product ZNQ-1432-B1was higher than or close to azoxystrobin against seven fungi. Moreover, it also exhibited good insecticidal activity. At the concentration of200ug/mL, its lethal rate reached62%against Aphis glycines Matsmura.The results of some target compounds against pathogens in vivo and spore germination in vitro indicated that compounds ZNQ-1422, ZNQ-1427, ZNQ-1428and ZNQ-1443completely inhibit colletotrichum lagenarium at the concentration of100ug/mL, and the inhibition rate of ZNQ-1427reached100%against Pyricularia oryzae and Botrytis cinerea on in vitro spore germination at the concentration of6.25ug/mL, so further researchs on these compounds are necessary.Eight possible configurations and conformations of target compounds were optimized by using the Gaussian09and confirmed the most stable conformation. The structure-activity relationship was studied by further molecular alignment and establishing CoMFA and CoMSIA model, including3D-QSAR studies on the insecticidal activity against Myzus persicae Sulzer and Hyalopterus amygdali Blanchard and the fungicidal activities against Physalospora piricola. The effect of steric field, electrostatic field, hydrophobic field, donor field and acceptor field on the activity of these compounds explained the structure-activity relationships and laid a foundation for the design of more active compounds.