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

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%similar to 91% yields, respectively. Their structures were fully characterized by IR, H-1 NMR, C-13 NMR, and HRMS data. Their antifungal activities were evaluated, and it showed that (R)-3-phenyl-7-methyl-7-hydroxy-2-octen-6-olide (5a) was the most active compound with the EC50 values in the range of 0.2 similar to 13.5 mu g/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)-5a, 5d and 5j had a significant impact on the structure and function of the hyphal cell wall of S. sclerotiorum mycelium.

Automated summary

The synthesis of racemic and optical 3-aryl-7-methyl-7-hydroxy-2-octen-6-olides was successfully achieved, and the (R)-3-phenyl-7-methyl-7-hydroxy-2-octen-6-olide showed the best antifungal activity against six phytopathogens. It could serve as a potential lead structure to be optimized.