3α-hydroxydeoxyartemisinin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧吡喃
• 英文名称: 3α-hydroxydeoxyartemisinin
• 英文别名: (1S,2R,4S,5R,8S,9R,12S,13R)-2-hydroxy-1,5,9-trimethyl-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecan-10-one
• 化学式: C₁₅H₂₂O₅
• 分子量: 282.337
• InChiKey: NTBCVGIABGYJEM-ZPOPJUNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  青蒿素 在 Aspergillus niger AS 3.795 作用下， 反应 96.0h， 以15%的产率得到3α-hydroxydeoxyartemisinin
  参考文献：
  名称：

  棘孢坎尼汉菌和黑曲霉对青蒿素的微生物转化

  摘要：

  进行了Cunninghamella echinulata（AS 3.3400）和黑曲霉（AS 3.795）对青蒿素1的微生物转化。获得两种产物，10β-羟基青蒿素2和3α-羟基脱氧青蒿素3。根据化学和光谱数据确定了它们的结构。10β-羟基青蒿素是一种新化合物。

  DOI：

  10.1016/s0040-4039(02)00812-2

文献信息

• Unified Mechanistic Framework for the Fe(II)-Induced Cleavage of Qinghaosu and Derivatives/Analogues. The First Spin-Trapping Evidence for the Previously Postulated Secondary C-4 Radical
  作者：Wen-Min Wu、Yikang Wu、Yu-Lin Wu、Zhu-Jun Yao、Cheng-Ming Zhou、Ying Li、Feng Shan

  DOI：10.1021/ja973080o

  日期：1998.4.1

  Qinghaosu and derivatives were easily reduced by ferrous sulfate in aqueous acetonitrile to give results different from those reported for other reducing systems. The unstable epoxide 7, a compound that was postulated earlier as a species responsible for the antimalarial activity, now has been isolated and characterized. The earlier speculative secondary C-4 radical has also been trapped with 2-me

  青蒿素及其衍生物在乙腈水溶液中很容易被硫酸亚铁还原，结果与其他还原体系报道的结果不同。不稳定的环氧化物 7 是一种较早被假定为具有抗疟活性的物质的化合物，现在已被分离和表征。早期推测的二级 C-4 自由基也被 2-甲基-2-亚硝基丙烷捕获，因此为自由基参与 QHS 型化合物的体外裂解提供了第一个直接证据。对于亚铁离子诱导的 1,2,4-三恶烷（即 QHS 等）裂解，提出了具有可互换自由基阴离子和可逆分子内自由基反应的统一机制。在此框架的基础上，结合反离子和溶剂效应的考虑，
• Transition-Metal-Catalyzed Group Transfer Reactions for Selective C−H Bond Functionalization of Artemisinin
  作者：Yungen Liu、Wenbo Xiao、Man-Kin Wong、Chi-Ming Che

  DOI：10.1021/ol071269r

  日期：2007.10.1

  carbenoid and nitrenoid C-H bond insertion reactions. With rhodium complexes as catalysts, lactone 11 was synthesized via carbene insertion reaction at the C16 position in 90% yield; oxazolidinone 13 was synthesized via nitrene insertion reaction at the C10 position in 87% yield based on 77% conversion; and sulfamidate 14 was synthesized via nitrene insertion reaction at the C8 position in 87% yield.

  通过过渡金属催化的分子内类胡萝卜素和氮烯基CH键插入反应合成了三种类型的新型青蒿素衍生物。以铑配合物为催化剂，通过卡宾插入反应在C16位合成内酯11，收率为90％。恶唑烷酮13是通过在C10位的亚硝基插入反应以77％的转化率以87％的产率合成的；通过C8位的亚硝基插入反应合成了氨基磺酸酯14，产率为87％。
• Interaction of Qinghaosu (Artemisinin) with Cysteine Sulfhydryl Mediated by Traces of Non-Heme Iron
  作者：Yikang Wu、Zheng-Yu Yue、Yu-Lin Wu

  DOI：10.1002/(sici)1521-3773(19990903)38:17<2580::aid-anie2580>3.0.co;2-j

  日期：1999.9.3

  The antimalarial action of 1,2,4-trioxanes such as qinghaosu (QHS) may take place through the mechanism shown schematically: In the presence of cysteine traces of non-heme iron (FeSO(4)) may cleave the peroxy bond of QHS rapidly, and the transient carbon-centered radical can attack the sulfur ligand to form a covalent bond.

  1,2,4-三恶烷类化合物如青蒿素（QHS）的抗疟作用可能通过示意性机理进行：在半胱氨酸中存在非血红素铁（FeSO（4））可能会裂解QHS的过氧键很快，以碳为中心的瞬态自由基会攻击硫配体以形成共价键。
• Chemical and electro-chemical reduction of qinghaosu (artemisinin)
  作者：Wen-Min Wu、Yu-Lin Wu

  DOI：10.1039/b007056o

  日期：——

  1,2,4-Trioxane is the essential segment of the new antimalarial agent qinghaosu 1, and hence its reduction is an important plausible process related to the bio-activity mode. An overview of its reduction and a careful examination of some reducing systems are presented herewith. Electrochemical reduction is a two-electron reduction, which is confirmed by the isolation of product deoxyqinghaosu. However, in the presence of a catalytic amount of FeII/III electrochemical reduction yields mainly the single-electron-reduction products, which are identified with the products from reduction of qinghaosu with one equivalent ferrous sulfate or a catalytical amount of FeII/III and excess of other reducing agents, such as ascorbic acid, or cysteine. These results mean that qinghaosu is reduced by ferrous ion and the resulting ferric ion is then reduced on the electrode to regenerate ferrous ion. In addition, qinghaosu could be reduced to deoxyqinghao by iodide, but not by bromide, and also could be reduced by the ascorbic acid–CuSO4 system to give free-radical reaction products.

  1,2,4-三恶烷是新型抗疟药物青蒿素1的重要组成部分，因此其还原是与生物活性模式相关的重要合理过程。本文介绍了其还原的概述以及对一些还原系统的仔细检查。电化学还原是双电子还原，通过产物脱氧青蒿素的分离证实了这一点。然而，在催化量的 FeII/III 存在下，电化学还原主要产生单电子还原产物，这与用一当量硫酸亚铁或催化量的 FeII/III 和过量硫酸亚铁还原青蒿素的产物相同。其他还原剂，例如抗坏血酸或半胱氨酸。这些结果意味着青蒿素被亚铁离子还原，然后生成的铁离子在电极上被还原以再生亚铁离子。此外，青蒿素可以被碘化物还原为脱氧青蒿，但不能被溴化物还原，也可以被抗坏血酸-CuSO4体系还原，得到自由基反应产物。
• A possible antimalarial action mode of qinghaosu (artemisinin) series compounds. Alkylation of reduced glutathione by C-centered primary radicals produced from antimalarial compound qinghaosu and 12-(2,4-dimethoxyphenyl)-12-deoxoqinghaosu
  作者：Dong-Ye Wang、Yu-Lin Wu

  DOI：10.1039/b006906j

  日期：——

  Antimalarial compound qinghaosu (1) and its phenyl derivative 2 were reacted with reduced glutathione (GSH) and Fe(II/III) to give, besides other known degradation products, an interesting adduct from a primary C-centered free radical and GSH. Because GSH plays a very important role in the cell cycle, this finding may eventually lead to a new understading of its mode of action.

  抗疟化合物青蒿素 (1) 及其苯基衍生物 2 与还原型谷胱甘肽 (GSH) 和 Fe(II/III) 反应，除了其他已知的降解产物外，还生成了一种有趣的以 C 为中心的自由基和 GSH 的加合物。由于 GSH 在细胞周期中起着非常重要的作用，这一发现可能最终导致对其作用方式的新认识。