deoxydihydroqinghaosu | 72807-92-2

• 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: deoxydihydroqinghaosu
• 英文别名: 2-deoxyDHA；Deoxydihydroartemisinin；(1S,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecan-10-ol
• CAS: 72807-92-2
• 化学式: C₁₅H₂₄O₄
• 分子量: 268.353
• InChiKey: JQGOBHOUYKYFPD-HVDUHBCDSA-N

物化性质

• 熔点：
  140 - 142oC
• 溶解度：
  氯仿（微溶）、甲醇（微溶、加热）
• 稳定性/保质期：
  Hygroscopic

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  Hygroscopic, stored in a refrigerator under an inert atmosphere.

反应信息

• 作为反应物：
  描述：

  deoxydihydroqinghaosu 在 三氟化硼乙醚 作用下， 生成 (1S,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-10-[[(1S,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecan-10-yl]oxy]-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecane 、 (1S,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-[[(1S,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecan-10-yl]oxy]-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecane
  参考文献：
  名称：

  Stereochemistry-Dependent Cytotoxicity of Some Artemisinin Derivatives

  摘要：

  We determined the cytotoxicity of some artemisinin derivatives against EN2 tumor cells using the MTT assay. Artemisinin (1) was clearly more cytotoxic than deoxyartemisinin (2), which lacks the endoperoxide bridge. Ether-linked dimers of dihydroartemisinin with defined stereochemistry were found to differ in the extent of cytotoxic effect on EN2 cells. The nonsymmetrical dimer (3) was more cytotoxic than the symmetrical dimer (4). The nonsymmetrical dimer of dihydrodeoxyartemisinin (5) lacking the endoperoxide bridges was also effective in the MTT assay, although less cytotoxic than 3 and 4. Similarly, the symmetrical dimer (6) was less effective than 5. Epoxides of artemisitene also showed that stereochemistry was an important factor for cytotoxicity. The results suggested that the endoperoxide bridge was not crucial for cytotoxicity to the tumor cells, but contributed to the cytotoxic effect apparently exerted by the ether linkage of the dimers. Flow cytometry data indicated that the dimers 3 and 4 caused an accumulation of the cells in the G(1)-phase of the cell cycle. In contrast, artemisinin (1) caused a slight increase of S-phase cells.

  DOI：

  10.1021/np9605495
• 作为产物：
  描述：

  青蒿琥酯 在 还原型辅酶II(NADPH)四钠盐 、 腺嘌呤黄素 作用下， 反应 3.0h， 以92%的产率得到deoxydihydroqinghaosu
  参考文献：
  名称：

  青蒿素对氧化亚乙基蓝和二氢黄素的简易氧化作用：与黄酮酶功能和抗疟疾作用机制的关系

  摘要：

  抗疟药亚甲蓝（MB）影响寄生虫黄素依赖性二硫键还原酶（如谷胱甘肽还原酶（GR））的氧化还原行为，该酶控制疟疾寄生虫中的氧化应激。还原的黄素腺嘌呤二核苷酸辅因子FADH 2引发还原为亚乙蓝（LMB），其被氧气氧化以生成活性氧（ROS）和MB。然后，MB充当NADPH的颠覆性底物，而NADPH通常是再生FADH 2所需的酶功能。MB与过氧化抗疟疾青蒿素衍生物青蒿琥酯之间的协同作用表明青蒿素具有互补的作用方式。我们发现青蒿素被MB和抗坏血酸（AA）或N生成的LMB转化苄基二氢神经酰胺（BNAH）在生理pH条件下在水性缓冲液中原位转化为单电子转移（SET）重排产物或双电子还原产物，后者以BNAH为主。AA和BNAH均不影响青蒿素。在有氧条件下，AA–MB SET反应会增强，并且此处获得的主要产物在结构上与一种据报道已在细胞内培养基中形成的此类产物密切相关。调用通过SET与青蒿素产生的​​酮基来解释

  DOI：

  10.1002/cmdc.201000225

文献信息

• The behaviour of qinghaosu (artemisinin) in the presence of heme iron(II) and (III)
  作者：Richard K. Haynes、Simone C. Vonwiller

  DOI：10.1016/0040-4039(95)02141-8

  日期：1996.1

  With hemin [chloroprotoporphyrin IX iron(III)] or hemin/cysteine in aqueous MeCN, oxygen loss from the peroxide bridge of qinghaosu takes place to give a precursor to desoxoqinghaosu, a known malaria-inactive metabolite, in low yield. Ring-opened forms of qinghaosu such as the free hydroperoxide or peroxyhemiacetal react with hemin and heme to give predominantly the diketone resulting from oxygen loss

  在含水MeCN中，使用血红素[氯原卟啉IX铁（III）]或血红素/半胱氨酸，会从qinghaosu的过氧化物桥中损失氧气，从而以低收率得到desoxoqinghaosu（一种已知的对疟疾无活性的代谢物）的前体。庆豪素的开环形式（例如游离氢过氧化物或过氧半缩醛）与血红素和血红素反应，主要产生二酮，这是由于过氧化物桥上的氧损失而引起的甲酰化。
• ——
  作者：Olutosin R. Idowu、Ai J. Lin、James M. Grace、James O. Peggins

  DOI：10.1023/a:1012185124972

  日期：——

  PURPOSE To study the reaction of artelinic acid with chemical model systems of cytochrome P-450 as a means of obtaining authentic samples of the putative metabolites necessary for identification of the mammalian metabolites of artelinic acid. METHODS Artelinic acid was reacted with different organic complexes of iron(II). The reaction products were isolated and characterized by NMR and thermospray

  目的研究青蒿酸与细胞色素P-450化学模型系统的反应，作为获得鉴定鉴定为青蒿酸哺乳动物代谢物所必需的推定代谢物的真实样品的一种手段。方法青蒿酸与铁（II）的不同有机络合物反应。分离反应产物，并通过NMR和热喷雾质谱表征。结果从这些反应中分离出5种化合物（假定为青蒿酸的代谢产物）并进行了明确鉴定，而另外两种化合物的身份尚待最终确认。结论通过化合物与可模拟细胞色素P-450催化异源生物代谢的亚铁配合物的反应，可制得可能的青蒿酸代谢产物标准品。
• Facile Oxidation of Leucomethylene Blue and Dihydroflavins by Artemisinins: Relationship with Flavoenzyme Function and Antimalarial Mechanism of Action
  作者：Richard K. Haynes、Wing-Chi Chan、Ho-Ning Wong、Ka-Yan Li、Wai-Keung Wu、Kit-Man Fan、Herman H. Y. Sung、Ian D. Williams、Davide Prosperi、Sergio Melato、Paolo Coghi、Diego Monti

  DOI：10.1002/cmdc.201000225

  日期：——

  oxygen with generation of ROS. Reduction of the artemisinin is proposed to occur via hydride transfer from LMB or the dihydroflavin to O1 of the peroxide. This hitherto unrecorded reactivity profile conforms with known structure–activity relationships of artemisinins, is consistent with their known ability to generate ROS in vivo, and explains the synergism between artemisinins and redox‐active antimalarial

  抗疟药亚甲蓝（MB）影响寄生虫黄素依赖性二硫键还原酶（如谷胱甘肽还原酶（GR））的氧化还原行为，该酶控制疟疾寄生虫中的氧化应激。还原的黄素腺嘌呤二核苷酸辅因子FADH 2引发还原为亚乙蓝（LMB），其被氧气氧化以生成活性氧（ROS）和MB。然后，MB充当NADPH的颠覆性底物，而NADPH通常是再生FADH 2所需的酶功能。MB与过氧化抗疟疾青蒿素衍生物青蒿琥酯之间的协同作用表明青蒿素具有互补的作用方式。我们发现青蒿素被MB和抗坏血酸（AA）或N生成的LMB转化苄基二氢神经酰胺（BNAH）在生理pH条件下在水性缓冲液中原位转化为单电子转移（SET）重排产物或双电子还原产物，后者以BNAH为主。AA和BNAH均不影响青蒿素。在有氧条件下，AA–MB SET反应会增强，并且此处获得的主要产物在结构上与一种据报道已在细胞内培养基中形成的此类产物密切相关。调用通过SET与青蒿素产生的​​酮基来解释
• Stereochemistry-Dependent Cytotoxicity of Some Artemisinin Derivatives
  作者：Aäron C. Beekman、Adriaan R. W. Barentsen、Herman J. Woerdenbag、Wim Van Uden、Niesko Pras、Antonius W. T. Konings、Farouk S. El-Feraly、Ahmed M. Galal、Håkan V. Wikström

  DOI：10.1021/np9605495

  日期：1997.4.1

  We determined the cytotoxicity of some artemisinin derivatives against EN2 tumor cells using the MTT assay. Artemisinin (1) was clearly more cytotoxic than deoxyartemisinin (2), which lacks the endoperoxide bridge. Ether-linked dimers of dihydroartemisinin with defined stereochemistry were found to differ in the extent of cytotoxic effect on EN2 cells. The nonsymmetrical dimer (3) was more cytotoxic than the symmetrical dimer (4). The nonsymmetrical dimer of dihydrodeoxyartemisinin (5) lacking the endoperoxide bridges was also effective in the MTT assay, although less cytotoxic than 3 and 4. Similarly, the symmetrical dimer (6) was less effective than 5. Epoxides of artemisitene also showed that stereochemistry was an important factor for cytotoxicity. The results suggested that the endoperoxide bridge was not crucial for cytotoxicity to the tumor cells, but contributed to the cytotoxic effect apparently exerted by the ether linkage of the dimers. Flow cytometry data indicated that the dimers 3 and 4 caused an accumulation of the cells in the G(1)-phase of the cell cycle. In contrast, artemisinin (1) caused a slight increase of S-phase cells.