(2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 140658-35-1

• 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: (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• CAS: 140658-35-1
• 化学式: C₂₉H₄₂O₁₄
• 分子量: 614.644
• InChiKey: DKWGUJHXKMKRPN-QRCOKFIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.29
• 重原子数：
  43.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  160.58
• 氢给体数：
  0.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 barium(II) oxide 作用下， 以 甲醇 为溶剂， 反应 4.5h， 以50.7%的产率得到(2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]oxane-3,4,5-triol
  参考文献：
  名称：

  Antimalarial activity of new dihydroartemisinin derivatives. 5. Sugar analogs.

  摘要：

  A series of dihydroartemisinin derivatives containing a sugar moiety was prepared in the search for analogues with good water solubility and high antimalarial activity. The preparation of the new compounds were achieved by treatment of dihydroartemisinin (2) with chlorotrimethylsilane in pyridine solution at -10-degrees-C to give a nearly quantitative Yield of 10-0-(trimethylsilyl)dihydroartemisinin (3), which was then condensed with 1-hydroxypolyacetylated sugars 5 to give dihydroartemisinin derivatives 7a-d. Deacetylation of intermediates 7 gave the desired sugar derivatives 8. The resulting derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Trimethylsilylated compound 3 is more effective than derivatives 7a-d, which possess activity comparable to or better than that of artemisinin itself. Deacetylated compounds 8a-d were substantially less active than 7 in both cell lines. In P. berghei-infected mice, 7a-c showed 5/5, 2/5, and 3/5 cures, respectively, at 320 mg/kg per day X 3, whereas 7d showed no activity at the same dosage. However, 7d did prolong the life span in 3/5 of the infected mice at 640 mg/kg per day X 3 dose level. Trimethylsilylated compound 3 was also the most effective among the compounds studied, with 5/5 cures at 80 mg/kg per day X 3. The deacetylated sugar derivatives 8a-d showed only slight in vivo antimalarial activity.

  DOI：

  10.1021/jm00087a021
• 作为产物：
  描述：

  dihydroartemisinin 在 吡啶 、 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 29.0h， 生成 (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(((3R,5aS,6R,8aS,9R,10S,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Antimalarial activity of new dihydroartemisinin derivatives. 5. Sugar analogs.

  摘要：

  A series of dihydroartemisinin derivatives containing a sugar moiety was prepared in the search for analogues with good water solubility and high antimalarial activity. The preparation of the new compounds were achieved by treatment of dihydroartemisinin (2) with chlorotrimethylsilane in pyridine solution at -10-degrees-C to give a nearly quantitative Yield of 10-0-(trimethylsilyl)dihydroartemisinin (3), which was then condensed with 1-hydroxypolyacetylated sugars 5 to give dihydroartemisinin derivatives 7a-d. Deacetylation of intermediates 7 gave the desired sugar derivatives 8. The resulting derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Trimethylsilylated compound 3 is more effective than derivatives 7a-d, which possess activity comparable to or better than that of artemisinin itself. Deacetylated compounds 8a-d were substantially less active than 7 in both cell lines. In P. berghei-infected mice, 7a-c showed 5/5, 2/5, and 3/5 cures, respectively, at 320 mg/kg per day X 3, whereas 7d showed no activity at the same dosage. However, 7d did prolong the life span in 3/5 of the infected mice at 640 mg/kg per day X 3 dose level. Trimethylsilylated compound 3 was also the most effective among the compounds studied, with 5/5 cures at 80 mg/kg per day X 3. The deacetylated sugar derivatives 8a-d showed only slight in vivo antimalarial activity.

  DOI：

  10.1021/jm00087a021