Zhan Yulian, Wu Yunshan, Xu Fangfang, Bai Yunpeng, Guan Yezhi, Williamson John S, Liu Bo
Guangxi Colleges and Universities Key Laboratory of Biomedical Sensing and Intelligent Instrument, School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541004, People's Republic of China; State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, People's Republic of China; Department of Medicinal Chemistry, University of Mississippi, University, MS 38677-1848, United States.
Fitoterapia. 2017 Jul;120:93-97. doi: 10.1016/j.fitote.2017.05.015. Epub 2017 May 30.
Microbial transformation of artemisinin (1) by Cunninghamella elegans was investigated. Four isolated products were identified as 6β-hydroxyartemisinin (2), 7α-hydroxyartemisinin (3), 7β-hydroxyartemisinin (4), and 6β,7α-dihydroxyartemisinin (5). The structures were elucidated by spectroscopic and X-ray crystallographic analysis. Product 5 is a novel compound and being reported here for the first time. It features two hydroxyl groups in its structure, and this is the first report on dihydroxylation of the artemisinin skeleton. Quantitative structure-activity relationship and molecular modeling studies indicate the modification of artemisinin skeleton will increase antimalarial activity and water solubility. The chemical syntheses of artemisinin derivatives at C6 or C7 position are impossible due to the lack of functional groups. 6β,7α-Dihydroxyartemisinin is hydroxylated at both 6β- and 7α-positions of artemisinin skeleton at the same time. Therefore, this new compound would be a good scaffold for further structural modification in the search for more potent antimalarial drugs.
研究了雅致小克银汉霉对青蒿素（1）的微生物转化。鉴定出四种分离产物为6β-羟基青蒿素（2）、7α-羟基青蒿素（3）、7β-羟基青蒿素（4）和6β,7α-二羟基青蒿素（5）。通过光谱和X射线晶体学分析阐明了其结构。产物5是一种新型化合物，首次在此报道。其结构中有两个羟基，这是青蒿素骨架双羟基化的首次报道。定量构效关系和分子模拟研究表明，青蒿素骨架的修饰将增加抗疟活性和水溶性。由于缺乏官能团，在C6或C7位进行青蒿素衍生物的化学合成是不可能的。6β,7α-二羟基青蒿素同时在青蒿素骨架的6β-和7α-位羟基化。因此，这种新化合物将是进一步结构修饰以寻找更有效的抗疟药物的良好骨架。
