(1R,2S,3aS,4S,7S,8R,8aR)-7-[(1S)-2-hydroxy-1-methylethyl]-2-[(4-methoxybenzyl)oxy]-1,4-dimethyl-1,2,3,3a,4,7,8,8a-octahydro-4,7-epidioxyazulen-8-ol | 1254986-28-1

• 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: (1R,2S,3aS,4S,7S,8R,8aR)-7-[(1S)-2-hydroxy-1-methylethyl]-2-[(4-methoxybenzyl)oxy]-1,4-dimethyl-1,2,3,3a,4,7,8,8a-octahydro-4,7-epidioxyazulen-8-ol
• 英文别名: (1S,2S,4S,5R,6R,7R,8S)-8-[(2S)-1-hydroxypropan-2-yl]-4-[(4-methoxyphenyl)methoxy]-1,5-dimethyl-9,10-dioxatricyclo[6.2.2.02,6]dodec-11-en-7-ol
• CAS: 1254986-28-1
• 化学式: C₂₃H₃₂O₆
• 分子量: 404.503
• InChiKey: MJNBTPWNJFVVRV-DMVSYFFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  77.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2S,3aS,4S,7S,8R,8aR)-7-[(1S)-2-hydroxy-1-methylethyl]-2-[(4-methoxybenzyl)oxy]-1,4-dimethyl-1,2,3,3a,4,7,8,8a-octahydro-4,7-epidioxyazulen-8-ol 在 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以85%的产率得到(1R,2S,3aS,4S,7S,8R,8aR)-7-[(1S)-2-hydroxy-1-methylethyl]-2-hydroxy-1,4-dimethyl-1,2,3,3a,4,7,8,8a-octahydro-4,7-epidioxyazulen-8-ol
  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：

  (3R,3aS,6S,6aS,8S,9R,9aR,9br)-8-[(4-methoxybenzyl)oxy]-3,6,9-trimethyl-6a,7,8,9,9a,9bhexahydro-6H-3a,6-epidioxyazuleno[4,5-b]furan-2(3H)-one 在 锂硼氢 、 水 、 氯化铵 作用下， 以 乙醚 为溶剂， 反应 1.0h， 以94%的产率得到(1R,2S,3aS,4S,7S,8R,8aR)-7-[(1S)-2-hydroxy-1-methylethyl]-2-[(4-methoxybenzyl)oxy]-1,4-dimethyl-1,2,3,3a,4,7,8,8a-octahydro-4,7-epidioxyazulen-8-ol
  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).