taccalonolide AN | 1415799-78-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: taccalonolide AN
• 英文别名: [(1S,2R,3R,5S,7S,9R,10R,11R,12S,14S,15R,16S,17S,22S,23S,24R,25R)-3,10,22,25-tetrahydroxy-11,15,17,22,23-pentamethyl-4,21-dioxo-8,20-dioxaheptacyclo[13.10.0.02,12.05,11.07,9.016,24.019,23]pentacos-18-en-14-yl] acetate
• CAS: 1415799-78-8
• 化学式: C₃₀H₄₀O₁₀
• 分子量: 560.642
• InChiKey: LOEZWMNSGZLOSK-HGMIYKCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  40
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  taccalonolide AN 在 二甲基二环氧乙烷 作用下， 以 二氯甲烷 为溶剂， 生成 taccalonolide AN 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
• 作为产物：
  描述：

  taccalonolide N 在 水 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 20.0h， 生成 taccalonolide AK 、 taccalonolide AN
  参考文献：
  名称：

  Hydrolysis Reactions of the Taccalonolides Reveal Structure–Activity Relationships

  摘要：

  The taccalonolides are microtubule stabilizers isolated from plants of the genus Tacca that show potent in vivo antitumor activity and the ability to overcome multiple mechanisms of drug resistance. The most potent taccalonolide identified to date, AJ, is a semisynthetic product generated from the major plant metabolite taccalonolide A in a two-step reaction. The first step involves hydrolysis of taccalonolide A to generate taccalonolide B, and then this product is oxidized to generate an epoxide group at C-22-C-23. To generate sufficient taccalonolide AJ for in vivo antitumor efficacy studies, the hydrolysis conditions for the conversion of taccalonolide A to B were optimized. During purification of the hydrolysis products, we identified the new taccalonolide AO (1) along with taccalonolide I. When the same hydrolysis reaction was performed on a taccalonolide E-enriched fraction, four new taccalonolides, assigned as AK, AL, AM, and AN (2-5), were obtained in addition to the expected product taccalonolide N. Biological assays were performed on each of the purified taccalonolides, which allowed for increased refinement of the structure-activity relationship of this class of compounds.

  DOI：

  10.1021/np400435t

文献信息

• TACCALONOLIDE MICROTUBULE STABILIZERS
  申请人：THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

  公开号：US20170313739A1

  公开（公告）日：2017-11-02

  The invention provides epoxytaccalonolide microtubule stabilizers and their use as anti-proliferative microtubule stabilizing agents.