新型异喹啉衍生物的设计合成及抑菌活性

Design,Synthesis and Antifungal Activity of Novel Isoquinoline Derivatives

利用仿生合成的策略,通过合理的药效团拼接,将二苯醚结构单元引入3,4-二氢异喹啉母核中,设计合成了15个新型的异喹啉衍生物;经核磁共振波谱和高分辨质谱确定了其结构.离体抑菌活性测试结果显示,在50 mg/L的测试浓度下,化合物Ic,Ie和Il对苹果轮纹病菌和小麦纹枯病菌的抑制率均超过93.0%,优于血根碱并与百菌清相当.化合物Il对小麦赤霉病菌的抑菌率为83.3%,远优于血根碱(64.2%)和百菌清(57.7%).另外,化合物Il对5种病菌的抑制率高于血根碱.

Based on biomimetic synthetic strategy and reasonable pharmacophore splicing,fifteen novel isoquinoline derivatives were designed and synthesized by introducing the active fragment of diphenyl ether into the 3,4-dihydroisoquinoline skeleton.Their chemical structures were confirmed by nuclear magnetic resonance(NMR)and high resolution mass spectrometry(HRMS).In vitro antifungal activity results showed that at 50 mg/L,the inhibition rates of compounds Ic,Ie and Il against Physalospora piricola and Rhizotonia cerealis were as high as 93.0%,which were better than Sanguinarine and equivalent to Chlorothalonil.The inhibition rate of compound Il against Fusarium graminearum was 83.3%,which was much better than Sanguinarine(64.2%)and Chlorothalonil(57.7%).In addition,the inhibition rate of compound Il against five plant pathogens was higher than that of Sanguinarine.