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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Synthesis and Antifungal Activity of Cedranone Derivatives Containing Oxime Esters
Xiao-Mei Pan1, Jun-You Jian1, Qiu-Ju Liu1
1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Natural Products Research Center of Guizhou Province, Guizhou Medical University, Guiyang, PR China.
Abstract:
In order to discover new natural product-based antifungal agents, cedrol was isolated from the essential oil of Cupressus funebris Endl. stems. Cedranone was synthesized from cedrol, and 26 oxime ester derivatives were designed and prepared. All derivatives were characterized by NMR and HRMS. Their antifungal activities against 12 phytopathogenic fungi were evaluated using the mycelial growth rate method. Compound 4J showed potent inhibitory activity against Phomopsis sp. (Phomopsis sp.), with an EC50 of 8.97 µM, which was significantly superior to pyrimethanil (EC50 = 150.36 µM). At 89.7 µM (10 × EC50), 4J displayed good preventive efficacy against kiwi fruit rot (71.57%). Notably, pyrimethanil at 1503.6 µM (10 × EC50) showed no obvious control effect and was even less effective than the untreated control. SEM and TEM observations revealed that 4J disrupted mycelial morphology and organelles. Preliminary mechanism studies indicated that 4J acts by targeting the fungal cell membrane, impairing its integrity and inducing intracellular content leakage. These results demonstrate that 4J is a promising antifungal candidate against Phomopsis sp.
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