Synthesis and Antifungal Activity of Novel 3-Caren-5-One Oxime Esters.
Synthesis and Antifungal Activity of Novel 3-Caren-5-One Oxime Esters.
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新型3-Caren-5-1肟酯的合成及其抗真菌活性
DOI：
10.3390/molecules22091538
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发表时间：
2017-09-12
期刊：
影响因子：
--
通讯作者：
Hu Q
中科院分区：
文献类型：
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作者：
Huang M;Duan WG;Lin GS;Li K;Hu Q
设计并通过多步反应合成了一系列新型3-癸烯-5-酮肟酯类化合物，旨在开发具有潜在抗真菌活性的化合物。首次用柱色谱法分离了中间体3-caren-5-酮肟的两个E-Z立体异构体。所有中间体和目标化合物的结构均经UV-Vis、FTIR、NMR、ESI-MS和元素分析确证。采用离体抑菌活性测定方法对目标化合物进行了初步活性评价。在50 μg/mL下，所述真菌包括黄瓜黑腐病菌、梨生轮纹孢菌、番茄早疫病菌、花生生尾孢菌、玉米赤霉、立枯丝核菌、玉米小斑病菌和圆形炭疽菌。目标化合物对苹果轮纹病菌的抑菌活性最好，其中化合物（Z）-4r（R = β-吡啶基），（Z）-4q（R = α-噻吩基），（E）-4f′（R = p-F Ph），（Z）-4i（R = m-Me Ph），（Z）-4 j（R = p-Me Ph），和（Z）-4p（R = α-呋喃基）的抑制率分别为97.1%、87.4%、87.4%、85.0%、81.9%和77.7%，显示出比商业杀真菌剂百菌清更好的抗真菌活性。化合物（Z）-4r（R = β-吡啶基）对所有供试真菌的抑菌率分别为76.7%、82.7%、97.1%、66.3%、74.7%、93.9%、76.7%和93.3%，与商品杀菌剂百菌清的抑菌活性相当。此外，目标肟酯的E-Z异构体的抑菌活性也存在明显差异。这些结果提供了一个令人鼓舞的框架，可能导致开发有效的新型抗真菌剂。
A series of novel 3-caren-5-one oxime esters were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Two E-Z stereoisomers of the intermediate 3-caren-5-one oxime were separated by column chromatography for the first time. The structures of all the intermediates and target compounds were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal activity of the target compounds was preliminarily evaluated by the in vitro method against Fusarium oxysporum f. sp. cucumerinum, Physalospora piricola, Alternaria solani, Cercospora arachidicola, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. The target compounds exhibited best antifungal activity against P. piricola, in which compounds (Z)-4r (R = β-pyridyl), (Z)-4q (R = α-thienyl), (E)-4f′ (R = p-F Ph), (Z)-4i (R = m-Me Ph), (Z)-4j (R = p-Me Ph), and (Z)-4p (R = α-furyl) had inhibition rates of 97.1%, 87.4%, 87.4%, 85.0%, 81.9%, and 77.7%, respectively, showing better antifungal activity than that of the commercial fungicide chlorothanil. Also, compound (Z)-4r (R = β-pyridyl) displayed remarkable antifungal activity against all the tested fungi, with inhibition rates of 76.7%, 82.7%, 97.1%, 66.3%, 74.7%, 93.9%, 76.7% and 93.3%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide chlorothanil. Besides, the E-Z isomers of the target oxime esters were found to show obvious differences in antifungal activity. These results provide an encouraging framework that could lead to the development of potent novel antifungal agents.