Synthesis And Antifungal Activity Of Pyridine Derivatives Bearing Oximes/Benzoyl Urea Moiety

Pyridine is an important Nitrogen-containing heterocyclic compound,and its derivatives usually posses broad biological activities such as antibacterial,insecticidal,herbicidal,anticancer activities,and become a hot research topic in the development of new drugs because of its high activity,high selectivity,low toxicity,low residue.The introduction of the pyridine ring in pesticide molecular design may improve biological activities.On the other hand,oxime ether,oxime ester and benzoyl urea are important groups with excellent biological activities.Currently,the way that combines the active groups with heterocyclic structure is one of the main directions in the new pesticide discovery and synthesis.Triadimefon and pyrifenox are two excellent ergosterol biosynthesis inhibitors,but they have inevitably made pathogenic fungi resistant due to the use of a longer time.Therefore,the continuous development of the compounds is more meaningful.In order to find high active fungicide,we have designed and synthesized four series of pyridine derivatives with oxime ether/oxime ester/benzoyl urea,and the target compounds were evaluated for their antifungal activity against two plant pathogens（B.Cinerea and S.sclerotiorum）by the mycelium growth rate method.The main research results are summarized as follows:1.The target compounds 3-phenyl propan-1-one oxime ethers bearing pyridine moiety（I）were prepared using 3-acetypyridine,benzaldehyde,substituted anilines and alkoxyamine hydrochlorides as starting materials via condensation,addition and oximation reactions.2.The target compounds Ⅱ Ⅲ were prepared according to fungicide pyrifenox and Triadimefon.Firstly,the intermediate 3,3-dimethyl-1-（pyridin-3-yl）-butan-2-one was designed and prepared using LDA,3-picoline and ethyl 2,2-dimethylpropionate as starting materials,and then ten kinds of 3,3-dimethyl-1-（pyridin-3-yl）-butan-2-oxime ethers（Ⅱ）were synthesized starting from the intermediate and various substituted O-benzylhydroxylamine hydrochloride.Additionally,thirteen kinds of 3,3-dimethyl-1-（pyridin-3-yl）-butan-2-oxime esters（Ⅲ）were synthesized starting from the intermediate,hydroxylamine hydrochlorideand and substituted benzoic acid via oximation and etherification reaction.3.The target compounds Ⅳwere synthesized by multi-step reactions from the starting materials of the intermediate,substituted benzamide,the compound 3,3-dimethyl-1-（pyridin-3-yl）-butan-2-ol was prepared via reductive reaction of the intermediate.4.The intermediates and target compounds were confirmed by IR,¹H NMR,¹³ C NMR,elemental analysis.The physicochemical properties and spectral data of the target compounds were analyzed and discussed in detail..5.All the novel target compounds were evaluated against Botrytis cinerea and Sclerotinia sclerotiorum by using mycelium growth rate method.The results showed that the target compounds Ⅰ have excellent antifungal activity,the EC₅₀ values of some compounds against Botrytis cinerea range from 3.09 to 4.23 μg/m L,the EC₅₀ values of these compounds between range from 1.81 to 2.93 μg/m L,were lower than those of the control agent of chlorothalonil（6.12 μg/m L and 3.27 μg/m L）,which showed higher activities than chlorothalonil.The target compounds Ⅱ showed moderate antifungal activity against the two kinds of fungi,the EC₅₀ valus of compounds against Botrytis cinerea range from 25.84 to59.26 μg/m L,and the EC₅₀ values of compounds against Sclerotinia sclerotiorum range from11.71 to 31.98 μg/m L,but the activity is lower than that of chlorothalonil.The target compounds III have higher biological activity than the target compounds Ⅱ,Such as Ⅲ_h andⅢ j showed the highest biological activity even better than the control fungicides chlorothalonil.The target compounds IV exhibited high antifungal activity,the EC₅₀ values of compounds against Botrytis cinerea range from 6.50 to 21.52 μg/m L,and the EC₅₀ values of compounds against Sclerotinia sclerotiorum range from 9.84 to 16.19 μg/m L,but at a concentration of 50 μg/m L,inhibition rate of the compounds except for IV_d and IV_j against Sclerotinia sclerotiorum has reached more than 90 %,higher than chlorothalonil significantly（79.26 %）.