taccalonolide AA epoxide | 1415751-19-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: taccalonolide AA epoxide
• 英文别名: [(1S,2S,3R,5R,7S,9S,10R,11S,12S,13S,14R,15R,16S,17S,18S,20S,23S,24S,25R,26R)-3,10,13,14-tetraacetyloxy-5,23-dihydroxy-11,15,17,23,24-pentamethyl-4,22-dioxo-8,19,21-trioxaoctacyclo[13.11.0.02,12.05,11.07,9.016,25.018,20.020,24]hexacosan-26-yl] acetate
• CAS: 1415751-19-7
• 化学式: C₃₈H₄₈O₁₇
• 分子量: 776.789
• InChiKey: IATNLGMMGLRZKD-GMQPNULGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  55
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  240
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  taccalonolide AA 在 二甲基二环氧乙烷 作用下， 以 二氯甲烷 为溶剂， 生成 taccalonolide AA epoxide
  参考文献：
  名称：

  Synthetic Reactions with Rare Taccalonolides Reveal the Value of C-22,23 Epoxidation for Microtubule Stabilizing Potency

  摘要：

  The taccalonolides are microtubule stabilizers isolated from plants of the genus Tacca. Taccalonolide AF is 231 times more potent than the major metabolite taccalonolide A and differs only by the oxidation of the C-22,23 double bond in A to an epoxy group in AF. In the current study, 10 other rare natural taccalonolides were epoxidized and in each case epoxidation improved potency. The epoxidation products of taccalonolide T and AI were the most potent, with IC50 values of 0.43 and 0.88 nM, respectively. These potent taccalonolides retained microtubule stabilizing effects, and T-epoxide demonstrated antitumor effects in a xenograft model of breast cancer. Additional reactions demonstrated that reduction of the C-6 ketone resulted in an inactive taccalonolide and that C-22,23 epoxidation restored its activity. These studies confirm the value of C-22,23 epoxidation as an effective strategy for increasing the potency of a wide range of structurally diverse taccalonolide microtubule stabilizers.

  DOI：

  10.1021/jm500619j