(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-[2-methylidene-3-[[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]methyl]but-3-enyl]-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane | 888735-68-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-[2-methylidene-3-[[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]methyl]but-3-enyl]-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
• CAS: 888735-68-0
• 化学式: C₃₆H₅₄O₈
• 分子量: 614.82
• InChiKey: IJRWADGSZHMTLV-AQZMOMLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.38
• 重原子数：
  44.0
• 可旋转键数：
  5.0
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  73.84
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-[2-methylidene-3-[[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]methyl]but-3-enyl]-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane 在 二异丁基氢化铝 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 18.83h， 生成 (4,5-bis(((3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)methyl)-1,2-phenylene)dimethanol
  参考文献：
  名称：

  Second Generation, Orally Active, Antimalarial, Artemisinin-Derived Trioxane Dimers with High Stability, Efficacy, and Anticancer Activity

  摘要：

  In only two steps and in 63% overall yield, naturally occurring 1,2,4-trioxane artemisinin (1) was converted into C-10-carba trioxane conjugated diene dimer 4. This new dimer was then transformed easily in one additional 4 + 2-cycloaddition step into phthalate dimer 5, and further modification led to bis-benzyl alcohol dimer 7 and its phosphorylated analogues 8 and 9. Bis-benzyl alcohol dimer 7 is the most antimalarially active in vitro, 10 times more potent than artemisinin (1). Bis-benzyl alcohol dimer 7 is approximately 1.5 times more orally efficacious in rodents than the antimalarial drug sodium artesunate and is about 37 times more efficacious than sodium artesunate via subcutaneous administration. Both dimers 5 and 7 are thermally stable neat even at 60 degrees C for 24 h. Phthalate dimer 5 is very highly growth inhibitory but not cytotoxic toward several human cancer cell lines; both dimers 5 and 7 very efficiently and selectively kill human cervical cancer cells in vitro in a dose-dependent manner with no cytotoxic effects on normal cervical cells.

  DOI：

  10.1021/jm058288w
• 作为产物：
  描述：

  双氢青蒿素 在 吡啶 、 4-二甲氨基吡啶 、 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 生成 (1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-[2-methylidene-3-[[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]methyl]but-3-enyl]-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
  参考文献：
  名称：

  Second Generation, Orally Active, Antimalarial, Artemisinin-Derived Trioxane Dimers with High Stability, Efficacy, and Anticancer Activity

  摘要：

  In only two steps and in 63% overall yield, naturally occurring 1,2,4-trioxane artemisinin (1) was converted into C-10-carba trioxane conjugated diene dimer 4. This new dimer was then transformed easily in one additional 4 + 2-cycloaddition step into phthalate dimer 5, and further modification led to bis-benzyl alcohol dimer 7 and its phosphorylated analogues 8 and 9. Bis-benzyl alcohol dimer 7 is the most antimalarially active in vitro, 10 times more potent than artemisinin (1). Bis-benzyl alcohol dimer 7 is approximately 1.5 times more orally efficacious in rodents than the antimalarial drug sodium artesunate and is about 37 times more efficacious than sodium artesunate via subcutaneous administration. Both dimers 5 and 7 are thermally stable neat even at 60 degrees C for 24 h. Phthalate dimer 5 is very highly growth inhibitory but not cytotoxic toward several human cancer cell lines; both dimers 5 and 7 very efficiently and selectively kill human cervical cancer cells in vitro in a dose-dependent manner with no cytotoxic effects on normal cervical cells.

  DOI：

  10.1021/jm058288w

文献信息

• WO2007/67333
  申请人：——

  公开号：——

  公开（公告）日：——