ethyl (2R)-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,8ahexahydroazulen-5-yl)propanoate | 1254986-24-7

• 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 (2R)-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,8ahexahydroazulen-5-yl)propanoate
• 英文别名: ethyl (2R)-2-[(2S,3R,3aS,8aS)-2-[(4-methoxyphenyl)methoxy]-3,8-dimethyl-4-oxo-2,3,3a,8a-tetrahydro-1H-azulen-5-yl]propanoate
• CAS: 1254986-24-7
• 化学式: C₂₅H₃₂O₅
• 分子量: 412.526
• InChiKey: BBKVNXASCIVCEF-LTDXUTRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (2R)-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,8ahexahydroazulen-5-yl)propanoate 在 cerium(III) chloride heptahydrate 、 sodium tetrahydroborate 、 盐酸 、 水 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.67h， 以85%的产率得到(3R,6aS,8S,9R,9aS,9br)-8-[(4-methoxybenzyl)oxy]-3,6,9-trimethyl-6a,7,8,9,9a,9b-hexahydroazuleno[4,5-b]furan-2(3H)-one
  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：

  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 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙二醇二甲醚 为溶剂， 反应 3.0h， 以72%的产率得到ethyl (2R)-2-((2S,3R,3aS,8aS)-2-[(4-methoxybenzyl)oxy]-3,8-dimethyl-4-oxo-1,2,3,3a,4,8ahexahydroazulen-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).