7-去乙酰基葛杜宁 | 10314-90-6

• 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
• 中文名称: 7-去乙酰基葛杜宁
• 英文名称: 7-Desacetylgedunin
• 英文别名: 7-deacetoxy-7α-hydroxygedunin；7-deacetoxy-7-hydroxygedunin；7-deacetyl-gedunin；7-deacetylgedunin；deacetylgedunin；(1S,2R,4S,7S,8S,11R,12R,17R,19R)-7-(furan-3-yl)-19-hydroxy-1,8,12,16,16-pentamethyl-3,6-dioxapentacyclo[9.8.0.02,4.02,8.012,17]nonadec-13-ene-5,15-dione
• CAS: 10314-90-6
• 化学式: C₂₆H₃₂O₆
• 分子量: 440.536
• InChiKey: HCEYJYMNIQHPPK-DXTZDJJUSA-N

物化性质

• 熔点：
  250-272 °C (decomp)
• 沸点：
  596.0±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  32
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  89.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-去乙酰基葛杜宁 在 sodium hydroxide 、 双氧水 作用下， 以 水 、 丙酮 为溶剂， 以68%的产率得到(1S,3aS,41R,4a1S,5R,10aR,12aS)-1-(furan-3-yl)-5-hydroxy-4a1,7,7,10a,12a-pentamethyl-4a1,5,6,6a,7,10a,10b,11,12,12a-decahydronaphtho[2,1-f][9,10]dioxireno[2,3-d]isochromene-3,8(1H,3aH)-dione
  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

文献信息

• Fluorinated and rearranged gedunin derivatives
  作者：Yukio Hitotsuyanagi、Kumiko Mitsui、Haruhiko Fukaya、Koichi Takeya

  DOI：10.1016/j.phytol.2012.04.011

  日期：2012.9

  When treated with (diethylamino)sulfur trifluoride (DAST), 11α-hydroxygedunin gave 11β-fluorogedunin and 9,11-didehydrogedunin, whereas deacetylgedunin afforded two skeletal rearranged products 6 and 7, in which the Me-30 had shifted from position 8 to position 7. Of those products, 11β-fluorogedunin and 6 were shown to be more cytotoxic than gedunin on P-388 leukemia cells.

  当用（二乙氨基）三氟化硫（DAST）处理时，11α-羟基葛根宁产生11β-氟葛根宁和9,11-二氢氢化葛宁素，而去乙酰基古丁宁提供两个骨架重排产物6和7，其中Me-30从位置8转移到位置7.在这些产品中，对P-388白血病细胞，11β-氟精蛋白和6的细胞毒性比精蛋白高。