Design,Synthesis And Bioactivity Of Novel Strobilurin Derivatives

The strobilurins are an outstanding new class of agricultural fungicides,and this class of fungicides is based on a group of natural lead derivatives of(E)-methylβ-methoxyacrylate,such as strobilurin A,oudemansin A and myxothiazol A.With their broad spectrum of activity,high activity at low rates of application and outstanding environmental tolerability,the strobilurins have been one of the most important classes of agricultural fungicides and might in the near future assume the number one position in the market.However,as we all know that the resistance appeared after the long term use of fungicides,new frame construction are needed to be found to keep or improve the biological activity.In order to search for novel strobilurin derivatives with high activities,according to the bioisosterism and the connecting principle of actively biological groups,nineteen series and seven kinds of two hundred and twenty-nine strobilurin derivatives were designed and synthesized in good to excellent yields.Their bioactivities,structure-activity relationship and spectral properties were studied,and many of them were found to show excellent fungicidal activities.This dissertation may be summarized as follows:The strobilurin derivatives are summarized in the paper,and the review describes in detail their main categorizationp,synthesis methods,biochemical mode of action and resistance risk.Two hundred and twenty-nine strobilurin derivatives were designed and synthesized by a multiple step synthetic procedures.Their structures were characterized by ^ⅠH NMR,MS spectroscopies, element quantitative analysis and X-Ray analysis.The results of bioactivity assay indicated that many compounds displayed excellent fungicidal activity against tested fungi at the concentration of 200 mg.L^-1,such asⅠ1a,Ⅰ1c,Ⅰ1m,Ⅰ1w,Ⅰ1x,Ⅰ3j,Ⅰ3l,Ⅳ1b,Ⅱ1a,Ⅱ1g,Ⅱ1i,Ⅱ1j,Ⅱ1k,Ⅱ1l,Ⅱ1p,Ⅱ1q,Ⅱ1r,Ⅱ3b,Ⅱ3c,Ⅱ3d,Ⅲ1a,Ⅲ1d,Ⅲ2d,Ⅲ2f,Ⅲ3a,Ⅲ3b,Ⅲ3c,Ⅲ3d,Ⅲ3e,Ⅲ3h,Ⅲ3j,Ⅲ3k,Ⅳ1f,Ⅳ1g,Ⅳ1k,Ⅳ1l,Ⅳ2g they showed 100%fungicidal activity against Pseudoperonospora cubensis,and the compoundsⅠ1a,Ⅰ1c,Ⅰ1e,Ⅰ1l,Ⅰ1m,Ⅰ3q,Ⅱ1b,Ⅱ1d,Ⅱ1h,Ⅲ1e,Ⅲ1f,Ⅲ2e,Ⅲ3f,Ⅲ3i,Ⅲ31,Ⅳ1a,Ⅳ1d,Ⅳ1e,Ⅳ1h,Ⅳ1i,Ⅳ1j,Ⅳ1m,Ⅳ2b also showed more than 80%fungicidal activity.Meanwhile,the compoundsⅢ1a,Ⅲ2f,Ⅳ1e,Ⅳ1k,Ⅳ1l showed 100%fungicidal activity against Sphaerotheca fuliginea at the concentration of 200 mg.L^-1, and the compoundsⅡ1b,Ⅱ1h,Ⅳ2b,Ⅳg,Ⅳ1a,Ⅳ1b,Ⅳ1c,Ⅳ1d,Ⅳ1h,Ⅳ1j,Ⅳ1m also showed more than 80%fungicidal activity.Especially the compoundsⅣ1k were more excellent against Pseudoperonospora cubensis and Sphaerotheca fuliginea than the commercial Kresoxim-methyl.The results of test indicated that all the target compounds did not displayed good herbicidal activity,however,some of them exhibited excellent in vivo insecticidal activity against Tetranychus cinnabarnus,Mythima separate,Aphis medicagini at the concentration of 250 mg.L^-1and 500 mg.L^-1, such asⅡ1d,Ⅱ1e,Ⅱ1h,Ⅱ1k,Ⅱ1l,they showed 100%insecticidal activity against Mythima separate at the concentration of 500 mg.L^-1,Especially the compoundsⅡ1h was more excellent with the 55%inhibition activity against Mythima separate at the concentration of 20 mg.L^-1,which indicated that the strobilurins scaffold could be identified as a novel insecticidal lead structure.Preliminary bioassay showed some strobilurin derivatives containing pyrazolines and benzothiazole showed excellent insecticidal or fungicidal activity,and the relationship of the biological activity and their structures were studied also.