3-芳基-7-甲基-7-羟基-2-辛烯-6-内酯类化合物的合成及杀菌活性

Synthesis and Antifungal Activity of 3-Aryl-7-methyl-7-hydroxy-2-octen-6-olide

为了优化3-苯基-7-甲基-7-羟基-2-辛烯-6-内酯的化学结构,通过环氧化-内酯化和Sharpless不对称双羟基化反应作为关键步骤,分别以61%~91%的收率实现了消旋及光活性3-芳基-7-甲基-7-羟基-2-辛烯-6-内酯类化合物的合成,其结构经过IR,^(1)H NMR,^(13)C NMR和HR-ESI-MS的表征.对它们的杀菌活性进行了评价,结果表明(R)-3-苯基-7-甲基-7-羟基-2-辛烯-6-内酯(5a)活性最好的化合物,对6种植物病原菌的EC_(50)值在0.2~13.5μg/mL范围,优于其(S)-异构体及消旋体混合物.它可以作为先导结构进行进一步结构优化.扫描电镜和透射电镜观测的结果显示,化合物(S)-5a,5d和5j对油菜菌核菌菌丝细胞的结构和功能有显著影响.

In order to optimize the structure of 3-phenyl-7-methyl-7-hydroxy-2-octen-6-olide, the synthesis of racemic and optical 3-aryl-7-methyl-7-hydroxy-2-octen-6-olides has been achieved via epoxidation-lactonization procedure and Sharpless asymmetric dihydroxylation as the key steps in 61%~91% yields, respectively. Their structures were fully characterized by IR, 1H NMR, 13C NMR, and HRMS data. Their antifungal activities were evaluated, and it showed that(R)-3-phenyl-7-methyl-7-hydroxy-2-octen-6-olide(5 a) was the most active compound with the EC_(50) values in the range of 0.2~13.5 μg/mL against the tested six phytopathogens, better than its(S)-isomer and racemic mixture. It would be the potential lead structure to be optimized. The scanning electron microscopy(SEM) and transmission electron microscopy(TEM) observation indicated that compounds(S)-5 a, 5 d and 5 j had a significant impact on the structure and function of the hyphal cell wall of S. sclerotiorum mycelium.