新型 3-蒈烯-5-酮肟酯的合成与抗真菌活性。

Synthesis and Antifungal Activity of Novel 3-Caren-5-One Oxime Esters.

机构信息

School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China.

出版信息

Molecules. 2017 Sep 12;22(9):1538. doi: 10.3390/molecules22091538.

DOI:10.3390/molecules22091538

PMID:28895932

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6151701/

Abstract

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 - 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 f. sp. , , , , , , and at 50 µg/mL. The target compounds exhibited best antifungal activity against , in which compounds ()- (R = -pyridyl), ()- (R = -thienyl), ()- (R = -F Ph), ()- (R = -Me Ph), ()- (R = -Me Ph), and ()- (R = -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 ()- (R = -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 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.

摘要

一系列新型 3-蒈烯-5-酮肟酯通过多步反应设计和合成，试图开发出有效的抗真菌剂。两种中间体 3-蒈烯-5-酮肟的非对映异构体首次通过柱色谱法分离。所有中间体和目标化合物的结构均通过 UV-Vis、FTIR、NMR、ESI-MS 和元素分析得到确认。采用体外法初步评价了目标化合物对 50μg/mL 下 f. sp.、、、、、、和的抗真菌活性。目标化合物对表现出最好的抗真菌活性，其中化合物 ()- (R = -吡啶基)、()-(R = -噻吩基)、()-(R = -F Ph)、()-(R = -Me Ph)、()-(R = -Me Ph)、()-(R = -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氯噻啉更好的抗真菌活性。此外，化合物 ()- (R = -吡啶基)对所有测试真菌均表现出显著的抗真菌活性，抑制率分别为 76.7%、82.7%、97.1%、66.3%、74.7%、93.9%、76.7%和 93.3%，显示出比商业杀真菌剂氯噻啉更好或相当的抗真菌活性。此外，还发现目标肟酯的对映异构体在抗真菌活性方面表现出明显差异。这些结果为开发有效的新型抗真菌剂提供了令人鼓舞的框架。