Synthesis And Biological Activities Of Novel Strobilurins Containing Phenylpyridine Moieties

Successful development of Strobilurin fungicides is a milestone in the fungicide history.It is another sort of highly efficient and broad-spectrum fungicide besides the previous benzimidazole and triazole fungicides,which features in high activity,environmental security,unique mode of action.Unfortunately,resistance had occurred and become prominent after years of field application.Compounding is a way to solution,however,to develop new fungicides with different mode of action is essential to solve the problem.In order to discover new Strobilurin analogues with higher biological activity,totally 114 novel compounds containing substituted benzene ring and N-containing heterocycles(94 compounds containing phenylpyridine moieties,12 compounds containing 1,4-dihydropyridine moieties,4 compounds containing phenylquinoline moieties and 4 compounds containing phenylpyrazine moieties)were designed and synthesized based on a detailed summary of the literatures.All these Strobilurin compounds synthesized are new.Their structures were characterized by 1H NMR,ESI-MS and IR analysis,and their biological activity test were conducted as well.In this paper,two series of compounds containing oximinoacetate moieties and N-phenylcarbamate moieties were designed and synthesized,which were detailed described in chapter 2 and chapter 3 respectively.The content of two chapter is narrated in a parallel manner:the second,third,fourth,fifth section refered to corresponding compounds,which are Strobilurin compounds containing phenylpyridine moieties,1,4-dihydropyridine moieties,phenylquinoline moieties and phenylpyrazine moieties in sequence.In the first section of chapter 2,synthesis of the intermediate methyl(E)-(2-chloromethyl)-?-oximinobenzeneacetate(?)was discussed;In the first section of chapter 3,synthesis of the intermediate methyl(2-(bromomethyl)phenyl)(methoxy)carbamate(?)was discussed.Strobilurins containing Hantzsch pyridine derivatives moieties were studied.Hantzsch 1,4-dihydropyridines and Hantzsch 1,4-dihydropyridines with cyclohexanone moieties were synthesized and oxidized to give corresponding compounds containing phenylpyridine moieties.These intermediates were coupled with the intermediate ? or? to yield the new strobilurins.Preliminary bioassays indicated that Strobilurins containing Hantzsch pyridine derivatives moieties have a certain fungicidal,insecticidal and herbicidal activity.Strobilurins containing substituted 2-pyridylbenzene moieties were studied.Intermediates 2-(pyridine-2-)phenol and 2-(pyridin-2-yl)benzene-1,3-diol were synthesized by the palladium catalyzed C-H activation acetoxylation and subsequently hydrolysis.Both of them were coupled with the intermediate ? or ? to yield new Strobilurins.Preliminary bioassays indicated that Strobilurins containing substituted 2-pyridylbenzene moieties were not so bioactive.Strobilurins containing substituted 3-pyridylbenzene moieties were studied.Suzuki coupling reaction was conducted with halopyridine and 3-Hydroxyphenylboronic acid to give the intermediate that containing substituted 3-pyridylbenzene moieties.Then they were reacted with the intermediate ? or ? to yield new Strobilurins.Preliminary bioassays indicated that this class of compounds were especially active against Pseudoperonospora cubensis:compounds ? 4ag exhibit 80%inhibitory rate at the concentration of 5 mg/L,that is close to azoxystrobin's inhibition of 82%.Compound I4an exhibited higher than 90%inhibitory rate against 5 tested target weeds;Compounds ? 4aa?? 4bd?? 4ad?? 4aj?? 4ak showed 100%of inhibitory activity against Myxosoma under the concentration of 500 mg/L.Strobilurins containing substituted 4-pyridylbenzene moieties were studied.Suzuki coupling reaction was conducted with halopyridine and 4-Hydroxyphenylboronic acid to give the intermediate that containing substituted 4-pyridylbenzene moieties.Then they were coupled with the intermediate ? or ? to yield new Strobilurins.Preliminary bioassays indicated that compound I 5ac was especially herbicidal active,which showed 100%inhibitory activity against 5 tested target weeds.This paper discussed the structure-activity relationship on the synthesized compounds containing phenylpyridine moieties.The results showed that the compounds whose third binding site of the substituted bezene ring that connected to substituted pyridine ring exhibit good fungicidal activity,electron-withdrawing substituents promoted the activity,and generally the activity enhenced with the electron-withdrawing ability increased.Some compounds whose second binding site of the substituted pyridine ring that connected to bezene ring exhibit good herbicidal activity or insecticidal activity,substituents chlorine atom or methyl group promoted the activity.The trifluoromethyl played a special role in promoting activity.