摘要
以胡椒酮为原料,将羰基肟化后再与取代吡唑发生O-酰化反应,合成了 42 个新型(Z)-/(E)-胡椒酮基吡唑-肟酯化合物(6a～6u,包括21 对Z/E异构体),采用核磁共振氢谱(1 H NMR)、核磁共振碳谱(13 C NMR)、傅里叶变换红外光谱(FT-IR)和高分辨质谱(HRMS)对目标产物的结构进行了表征,并通过单晶X射线衍射(SC-XRD)分析了其Z/E构型.离体生物活性测试结果表明:当质量浓度为50 mg/L时,(Z)-/(E)-胡椒酮基吡唑-肟酯化合物对黄瓜枯萎病菌、花生褐斑病菌、苹果轮纹病菌、番茄早疫病菌、小麦赤霉病菌、水稻纹枯病菌、玉米小斑病菌和西瓜炭疽病菌这8 种植物病原菌,均表现出一定的抑菌活性且受其Z/E 构型影响显著,尤其对番茄早疫病菌的抑制活性最好,其中化合物(Z)-胡椒酮基(3′,5′-二三氟甲基)苯基吡唑-肟酯((Z)-6o)、(Z)-胡椒酮基(p-三氟甲基)苯基吡唑-肟酯((Z)-6u)、(Z)-胡椒酮基(p-硝基)苯基吡唑-肟酯((Z)-6p)、(E)-胡椒酮基(p-硝基)苯基吡唑-肟酯((E)-6p)、(Z)-胡椒酮基(p-三氟甲氧基)苯基吡唑-肟酯((Z)-6g)和(E)-胡椒酮基(o-氟)苯基吡唑-肟酯((E)-6i)对番茄早疫病菌的抑制率分别为83.8%、78.7%、76.3%、76.3%、74.8%和74.3%,而化合物(Z)-6u对苹果轮纹病菌的抑制率达82.5%,均优于阳性对照百菌清.采用比较分子场分析(CoMFA)方法对目标化合物Z构型对番茄早疫病菌抑制活性的三维定量构效关系(3D-QSAR)进行了初步探讨,建立了合理有效的 3D-QSAR模型(r2 = 0.928,q2 =0.732).
Abstract
Using piperitone as the raw material,42 novel(Z)-/(E)-piperitone-based pyrazole-oxime ester(compounds 6a-6u,including 21 pairs of Z/E isomers)were synthesized through O-acylation reactions with substituted pyrazoles after carbonyl oximation.The structures of the target products were characterized using proton-1 nuclear magnetic resonance spectrum(1 H NMR),carbon-13 nuclear magnetic resonance spectrum(13 C NMR),Fourier-transform infrared spectroscopy(FT-IR),and high-resolution mass spectrometry(HRMS).The Z/E configurations of the compounds were determined by single-crystal X-ray diffraction analysis(SC-XRD).In vitro bioactivity tests showed that the(Z)-/(E)-piperitone-based pyrazole-oxime ester compounds exhibited certain antifungal activities against eight plant pathogenic bacteria,including Fusarium oxysporum,Cercospora arachidicola,Physalospora piricola,Alternaria solani,Gibberella zeae,Rhizoctonia solani,Bipolaris maydis,and Colleterichum orbiculare,at a mass concentration of 50 mg/L.The antibacterial activity was significantly influenced by the Z/E configurations of the compounds,and their activities against A.solani were found to be the most efficient.Wherein,(Z)-piperitone-based(3′,5′-difluoromethyl)phenyl pyrazole-oxime ester((Z)-6o),(Z)-piperitone-based(p-trifluoromethyl)phenyl pyrazole-oxime ester((Z)-6u),(Z)-piperitone-based(p-nitro)phenyl pyrazole-oxime ester((Z)-6p),(E)-piperitone-based(p-nitro)phenyl pyrazole-oxime ester((E)-6p),(Z)-piperitone-based(p-trifluoromethoxy)phenyl pyrazole-oxime ester((Z)-6g),and(E)-piperitone-based(o-fluoro)phenyl pyrazole-oxime ester((E)-6i)exhibited the inhibition rates of 83.8%,78.7%,76.3%,76.3%,74.8%,and 74.3%,respectively,against A.solani.And compound(Z)-6u showed the inhibition rate of 82.5%against P.piricola,which was better than that of the positive control chlorothalonil.The three-dimensional quantitative structure-activity relationship(3D-QSAR)model(r2 = 0.928,q2 = 0.732)for the inhibitory activity of(Z)-piperitone-based pyrazole-oxime ester compounds against A.solani was established using comparative molecular field analysis(CoMFA)method.
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