(1S,3aS,41R,4a1S,5R,10aR,12aS)-1-(furan-3-yl)-4a1,7,7,10a,12a-pentamethyl-3,8-dioxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl carbamate | 1072032-72-4

• 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: (1S,3aS,41R,4a1S,5R,10aR,12aS)-1-(furan-3-yl)-4a1,7,7,10a,12a-pentamethyl-3,8-dioxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl carbamate
• CAS: 1072032-72-4
• 化学式: C₂₇H₃₃NO₇
• 分子量: 483.562
• InChiKey: RLYRPNDCNTZDFS-MYECLKLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  35.0
• 可旋转键数：
  2.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  121.36
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  7-去乙酰基葛杜宁 、 三氯乙酰异氰酸酯 在 甲醇 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 以97%的产率得到(1S,3aS,41R,4a1S,5R,10aR,12aS)-1-(furan-3-yl)-4a1,7,7,10a,12a-pentamethyl-3,8-dioxo-1,3,3a,4a1,5,6,6a,7,8,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]oxireno[2,3-d]isochromen-5-yl carbamate
  参考文献：
  名称：

  Gedunin, a Novel Hsp90 Inhibitor: Semisynthesis of Derivatives and Preliminary Structure−Activity Relationships

  摘要：

  Gedunin (1), a tetranortriterpenoid isolated from the Indian neern tree (Azadirachta indica), was recently shown to manifest anticancer activity via inhibition of the 90 kDa heat shock protein (Hsp90) folding machinery and to induce the degradation of Hsp90-dependent client proteins similar to other Hsp90 inhibitors. The mechanism of action by which gedunin induces client protein degradation remains undetermined, however, prior studies have demonstrated that it does not bind competitively versus ATP. In an effort to further probe the mechanism of action, 19 semisynthetic derivatives of gedunin were prepared and their antiproliferative activity against MCF-7 and SkBr3 breast cancer cells determined. Although no compound was found to exhibit antiproliferative activity more effective than the natural product, functionalities critical for antiproliferative activity have been identified.

  DOI：

  10.1021/jm8007486