ethyl 2-hydroxy-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,5,6,8a-octahydroazulen-5-yl)propanoate | 1254986-22-5

• 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: ethyl 2-hydroxy-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,5,6,8a-octahydroazulen-5-yl)propanoate
• 英文别名: ethyl 2-[(2S,3R,3aS,8aS)-2-[(4-methoxyphenyl)methoxy]-3,8-dimethyl-4-oxo-2,3,3a,5,6,8a-hexahydro-1H-azulen-5-yl]-2-hydroxypropanoate
• CAS: 1254986-22-5
• 化学式: C₂₅H₃₄O₆
• 分子量: 430.541
• InChiKey: FXCXKZREPKJDDJ-IWFNGMLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-hydroxy-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,5,6,8a-octahydroazulen-5-yl)propanoate 在 双[Α,Α-双(三氟甲基)苯甲醇合]二苯硫 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以99%的产率得到ethyl (2Z)-2-[(2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-2,3,3a,4,6,8ahexahydroazulen-5(1H)-ylidene]propanoate
  参考文献：
  名称：

  Design, Synthesis, and Development of Novel Guaianolide-Endoperoxides as Potential Antimalarial Agents

  摘要：

  Design and synthesis of a guaianolide-endoperoxide (thaperoxide) 3 was pursued as a new antimalarial lead which was found to be noncytotoxic as compared to the natural product lead thapsigargin 2. Several analogues of 3 were successfully synthesized and found to be comparable to derivatives of artemisinin 1 in in vitro antimalarial assay. Among the synthesized compounds, 22 showed excellent in vitro potency against the cultured parasites (W2 IC50 = 13 nM) without apparent cytotoxicity. Furthermore, SAR trends in thaperoxide analogues are presented and explained with the help of docking studies in the homology model of PfSERCA(PfATP6).

  DOI：

  10.1021/jm1006462
• 作为产物：
  描述：

  丙酮酸乙酯 、 (2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-1,2,3,3a,4,5,6,8a-octahydroazulen-4-one 在 sodium hexamethyldisilazane 、 水 、 氯化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以84%的产率得到ethyl 2-hydroxy-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,5,6,8a-octahydroazulen-5-yl)propanoate
  参考文献：
  名称：

  Design, Synthesis, and Development of Novel Guaianolide-Endoperoxides as Potential Antimalarial Agents

  摘要：

  Design and synthesis of a guaianolide-endoperoxide (thaperoxide) 3 was pursued as a new antimalarial lead which was found to be noncytotoxic as compared to the natural product lead thapsigargin 2. Several analogues of 3 were successfully synthesized and found to be comparable to derivatives of artemisinin 1 in in vitro antimalarial assay. Among the synthesized compounds, 22 showed excellent in vitro potency against the cultured parasites (W2 IC50 = 13 nM) without apparent cytotoxicity. Furthermore, SAR trends in thaperoxide analogues are presented and explained with the help of docking studies in the homology model of PfSERCA(PfATP6).

  DOI：

  10.1021/jm1006462

文献信息

• Design, Synthesis, and Development of Novel Guaianolide-Endoperoxides as Potential Antimalarial Agents
  作者：Lingzhi Sun、Falgun Shah、Mohamed A. Helal、Yunshan Wu、Yakambram Pedduri、Amar G. Chittiboyina、Jiri Gut、Philip J. Rosenthal、Mitchell A. Avery

  DOI：10.1021/jm1006462

  日期：2010.11.11

  Design and synthesis of a guaianolide-endoperoxide (thaperoxide) 3 was pursued as a new antimalarial lead which was found to be noncytotoxic as compared to the natural product lead thapsigargin 2. Several analogues of 3 were successfully synthesized and found to be comparable to derivatives of artemisinin 1 in in vitro antimalarial assay. Among the synthesized compounds, 22 showed excellent in vitro potency against the cultured parasites (W2 IC50 = 13 nM) without apparent cytotoxicity. Furthermore, SAR trends in thaperoxide analogues are presented and explained with the help of docking studies in the homology model of PfSERCA(PfATP6).