TA-NaBH4-12 | 128146-57-6

• 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: TA-NaBH4-12
• 英文别名: [(1S,2S,3R,4S,5S,7S,9S,10R,11S,12S,13S,14R,15R,16S,17S,22S,23S,24R,25R)-10,13,14-triacetyloxy-3,22,25-trihydroxy-11,15,17,22,23-pentamethyl-21-oxo-8,20-dioxaheptacyclo[13.10.0.02,12.05,11.07,9.016,24.019,23]pentacos-18-en-4-yl] acetate
• CAS: 128146-57-6
• 化学式: C₃₆H₄₈O₁₄
• 分子量: 704.769
• InChiKey: YKLYKAAJPRRFJN-BWECBHOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  50
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  205
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  TA-NaBH4-12 在 二甲基二环氧乙烷 作用下， 以 二氯甲烷 为溶剂， 生成 [(1S,2S,3R,4S,5S,7S,9S,10R,11S,12S,13S,14R,15R,16S,17S,18S,20S,23S,24S,25R,26R)-10,13,14-triacetyloxy-3,23,26-trihydroxy-11,15,17,23,24-pentamethyl-22-oxo-8,19,21-trioxaoctacyclo[13.11.0.02,12.05,11.07,9.016,25.018,20.020,24]hexacosan-4-yl] acetate
  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：

  箭根薯酮内酯B 在 甲醇 、 sodium tetrahydroborate 作用下， 反应 48.17h， 生成 TA-NaBH4-12 、 [(1S,2S,3R,4S,5S,7S,9S,10R,11S,12S,13S,14R,15R,16S,17S,22S,23S,24R,25R)-10,14-diacetyloxy-3,4,22,25-tetrahydroxy-11,15,17,22,23-pentamethyl-21-oxo-8,20-dioxaheptacyclo[13.10.0.02,12.05,11.07,9.016,24.019,23]pentacos-18-en-13-yl] acetate
  参考文献：
  名称：

  [EN] TACCALONOLIDE MICROTUBULE STABILIZERS
  [FR] STABILISATEURS TACCALONOLIDES DE MICROTUBULES

  摘要：

  公开号：

  WO2018112391A8

文献信息

• [EN] NEW TACCALONOLIDE MICROTUBULE STABILIZERS<br/>[FR] NOUVEAUX STABILISATEURS TACCALONOLIDES DE MICROTUBULES
  申请人：UNIV TEXAS

  公开号：WO2012170573A3

  公开（公告）日：2013-06-13
• 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.
• [EN] TACCALONOLIDE MICROTUBULE STABILIZERS<br/>[FR] STABILISATEURS TACCALONOLIDES DE MICROTUBULES
  申请人：UNIV TEXAS

  公开号：WO2018112391A8

  公开（公告）日：2019-07-11
• Synthetic Reactions with Rare Taccalonolides Reveal the Value of C-22,23 Epoxidation for Microtubule Stabilizing Potency
  作者：Jiangnan Peng、April L. Risinger、Jing Li、Susan L. Mooberry

  DOI：10.1021/jm500619j

  日期：2014.7.24

  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.