Studies On The Systemic Acquired Resistance Based Fungicidal Lead Optimization And Their Biological Activity

Plant elicitors as a novel green pesticide are always applied with insecticides or fungicides as mixture in agricultural practice.To find novel fungicide with systemic acquired resistance activity,by principles of pro-pesticide,four series containing total99 novel heterocyclic compounds were designed and synthesized by combination of potential systemic acquired resistance substructure 3,4-dichloroisothiazole and1,2,3-thiadiazole with strobilurins,acrylamido morpholine,triazole and imidazole fungicide leads.The chemical structures of all the target compounds were characterized by NMR,HRMS or elemental analysis.Crystals of the representative compounds of each series were cultured and confirmed by X-ray diffraction analysis.Meanwhile,the fungicidal activity and anti-TMV activity of all the target compounds and some intermediates compounds were systematically screened and evaluated.The results are as follows:A total of 47 new compounds of series ? derivatives were designed and synthesized by combining strobilurins fungicide lead with 3,4-dichloroisothiazole,1,2,3-thiadiazole and thiazolylpiperidine.Bioassay results showed that compounds I-1,I-4,I-6,I-7,I-10,I-12,I-27,and I-29 are broad spectrum antifungal activities,especially I-12 exhibited excellent activities with EC₅₀ at 0.07?g/mL against Sclerotinia sclerotiorum and EC₅₀ at 0.49?g/mL against Phytophthora infestans?Mont?de Bary,similar to the positive control azoxystrobin.Compound I-27 showed antifungal activities against Gibberella zeae,S.sclerotiorum and Rhizoctonia cerealis with EC₅₀ of 2.68,0.44 and 0.01?g/mL,respectively,their activities were more better than those of azoxystrobin.Field experiments showed that Compound I-12 and I-27 showed significantly better efficacy against Sphaerotheca fuliginea than that of azoxystrobin and trifloxystrobin;I-12 and I-27 also showed significantly better ativity against Pseudoperponspora cubensis than that of trifloxystrobin and similar efficacy to pyraclostrobin.I-12 also showed 79%systemic acquired resistance for tobacco against tobacco mosaic virus?TMV?at 100?g/mL,similar to the positive controls ningnanmycin and TDL.A total of 14 new compounds of series ? derivatives were designed and synthesized by combining fungicide lead acrylamido morpholine with3,4-dichloroisothiazole,1,2,3-thiadiazole and thiazolylpiperidine.Bioassay results showed that series of ? compounds did not exhibit good fungicidal activity.Only compound II-1 provided a completed protection against P.cubensis in vivo at 100?g/mL,which were same activity as dimethomorph and pyrimorph.Meanwhile,II-1also showed 60%anti-TMV activity with induction model as plant elicitor at 100?g/mL,which was similar to that of the positive control TDL.A total of 9 new compounds of series ? derivatives were designed and synthesized by combining triazole fungicide lead with 3,4-dichloroisothiazole and1,2,3-thiadiazole.Bioassay results showed that most of series ? compounds performed well in vitro fungicidal activity;in particular,compound III-2 showed excellent activity against B.cinerea,R.cerealis and P.piricola with EC₅₀ of 6.98,2.73 and 3.07?g/mL,which were significantly better than those of the positive control flufenol.Additionally,compound III-2 showed 81%of inactivation anti-TMV activity at 100?g/mL,similar to the positive control virazol.Compound III-2 also showed 61%of systemic acquired resistance anti-TMV activity,that was similar to those of tiadinil and isotianil.A total of 15 new compounds of series ? derivatives were obtained by combining imidazole with 3,4-dichloroisothiazole.Another design model was adopt to the development of series ?.Firstly,the target compound skeleton was designed basing on imazalil,and optimized by homology modeling and molecular docking.The potential active molecules were then synthesized,and their antifungical activities and mode of action were evaluated.Bioassay results showed that ?-R-7,?-R-11,?-R-12 and ?-S-11 are broad spectrum with commendable antifungal activities compared to the positive controls tioconazole and imazalil.Among them,?-R-7showed excellent inhibition against R.cerealis with an EC₅₀ of 0.02?g/mL.Additionally,?-S-11 provided a completed protection against B.cinerea in vivo at100?g/mL as did with Imazalil and Tioconazole.?-R-1 at 1.56?g/mL showed 90%inhibition activity against P.cubensis,that was better than the positive controls imazalil?10%?and tioconazole?10%?.Based on Q-PCR testing and microscopy observations,?-R-12 could inhibit the cell wall formation through the inhibition upon BcCYP51?feedback regulation gene?gene expression system,similar mode of action as tioconazole and imazalil.All the bioassay results indicated the efficiency of series ? molecular design;and established a new model for further development of novel pesticides.The results of this thesis provided theoretical basis for development of novel fungicide with both fungicidal and systemic acquired resistance,this had important meaning for lower the pesticide application amount in the agricultural environment.