Further evidence for the participation of primary carbon-centered free radicals in the antimalarial action of the qinghaosu (artemisinin) series of compounds
Further evidence for the participation of primary carbon-centered free radicals in the antimalarial action of the qinghaosu (artemisinin) series of compounds
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DOI：
10.1039/b008145k
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Dongyue Wang;Yu‐lin Wu;Yikang Wu;Jie Liang;Ying Li
中科院分区：
文献类型：
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作者：
Dongyue Wang;Yu‐lin Wu;Yikang Wu;Jie Liang;Ying Li
1，3-二甲氧基苯与O-乙酰基二氢青蒿素经Friedel-Crafts烷基化反应，得到12-（2，4-二甲氧基苯基）脱氧青蒿素2和2′的一对11位差向异构体。11β-差向异构体2的抗疟活性与蒿甲醚相当。化合物2与亚铁离子或L-半胱氨酸以及催化量的亚铁离子反应，得到一系列衍生自先前假定的C-中心自由基，特别是初级C-中心自由基的产物。然而，11α-差向异构体2′对亚铁离子几乎是惰性的，并且也显示出低的抗疟活性。自由基介导产物的鉴定以及化学反应性与生物活性之间的相关性再次为碳中心初级自由基在青蒿素系列化合物抗疟活性中的关键作用提供了证据。
Friedel–Crafts alkylation of 1,3-dimethoxybenzene with O-acetyldihydroqinghaosu gave a pair of 11-epimers of 12-(2,4-dimethoxyphenyl)deoxoqinghaosu 2 and 2′. The antimalarial activity of 11β-epimer 2 was comparable with that of artemether. Compound 2 reacted smoothly with ferrous ions or L-cysteine and catalytic amounts of ferrous ions to give a series of products derived from the previously postulated C-centered free radical, in particular the primary C-centered free radical. However, 11α-epimer 2′ was almost inert to ferrous ions and also showed low antimalarial activity. The identification of free radical mediated products and the correlation between chemical reactivity and bio-activity once again provided evidence for the key role of primary carbon-centered free radicals in the antimalarial activity of the qinghaosu series of compounds.