箭根薯酮内酯A | 108885-68-3

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 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
• 中文名称: 箭根薯酮内酯A
• 中文别名: 根薯酮内酯A
• 英文名称: taccalonolide A
• 英文别名: [(1S,2S,3R,5S,7S,9S,10R,11R,12S,13S,14R,15R,16S,17S,22S,23S,24R,25R)-10,14,25-triacetyloxy-3,22-dihydroxy-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-13-yl] acetate
• CAS: 108885-68-3
• 化学式: C₃₆H₄₆O₁₄
• 分子量: 702.753
• InChiKey: PTTJLTMUKRRHAT-VJAKQJMOSA-N

物化性质

• 沸点：
  776.8±60.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  50
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  202
• 氢给体数：
  2
• 氢受体数：
  14

制备方法与用途

生物活性

Taccalonolide A 是一种微管稳定剂，是从 Tacca chantrieri 中分离得到的类固醇，具有细胞毒性和抗疟疾活性。该化合物能够引起 G2-M 期滞留、Bcl-2 磷酸化，并引发细胞凋亡。此外，在体外实验中，Taccalonolide A 对过表达 P 糖蛋白 (Pgp) 和多药耐药蛋白 7 (MRP7) 的细胞系表现出显著抑制作用，其中对 SK-OV-3 细胞的生长抑制 IC50 值为 622 nM。

靶点

微管

反应信息

• 作为反应物：
  描述：

  箭根薯酮内酯A 在 水 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 以80%的产率得到箭根薯酮内酯B
  参考文献：
  名称：

  使用半合成生成的替卡洛洛利微管稳定剂定义了C-7或C-15处的单酰氧基部分以及C-7和C-25处的二取代的影响

  摘要：

  塔卡洛洛尼酯是一类独特的从Tacca spp分离得到的微管稳定剂。具有抗药性肿瘤的功效。我们以前的研究表明，与带有C-15羟基的AJ相比，C-15乙酰氧基他克洛奈德（AF）具有更好的体内抗肿瘤功效。为了进一步改善这类化合物的体内功效，我们半合成和测试了28种新的塔克拉波内酯的生物活性，这些新化合物在C-7或C-15处具有单取代基，在C-7和C-25处具有取代基。从甲酸到蒽醌-2-羰基氯的取代基种类繁多。所得具有多种C-7 / C-15 / C-25修饰的他卡洛洛内酯类似物显示出IC 50值从2.4 nM到> 20μM，可进行广泛的体外结构活性评估。由于C-7或C-15处取代基的水解，无论大小或空间体积如何，这种半合成策略均不能提供具有改善的治疗窗口的他克洛奈德。然而，当在肿瘤内给药时，在抗药性异种移植模型中，两个最有效的新他克洛内酯在C-7或C-15处具有异戊酸酯修饰，表现出有效且高度持久

  DOI：

  10.1021/acs.jnatprod.7b00967
• 作为产物：
  描述：

  乙酸酐 、 箭根薯酮内酯B 反应 48.0h， 生成 [(1S,2S,3R,5S,7S,9S,10R,11R,12S,13S,14R,15R,16S,17S,22S,23R,24R,25R)-3,10,14,22-tetraacetyloxy-25-hydroxy-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-13-yl] acetate 、 箭根薯酮内酯A
  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

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

  公开号：US20140357608A1

  公开（公告）日：2014-12-04

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

  本发明提供了环氧紫杉醇微管稳定剂及其作为抗增殖微管稳定剂的用途。
• Taccalonolide microtubule stabilizers
  申请人：THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

  公开号：US09340572B2

  公开（公告）日：2016-05-17

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

  本发明提供了环氧萜内酯微管稳定剂及其作为抗增殖微管稳定剂的应用。
• [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
• Identification and Biological Activities of New Taccalonolide Microtubule Stabilizers
  作者：Jiangnan Peng、April L. Risinger、Gary A. Fest、Evelyn M. Jackson、Gregory Helms、Lisa A. Polin、Susan L. Mooberry

  DOI：10.1021/jm200757g

  日期：2011.9.8

  The taccalonolides are a unique class of microtubule stabilizers that do not bind directly to tubulin. Three new taccalonolides, Z, AA, and AB, along with two known compounds, taccalonolides R and T, were isolated from Tacca chantrieri and Tacca integrifolia. Taccalonolide structures were determined by 1D and 2D NMR methods. The biological activities of the new taccalonolides, as well as taccalonolides A, B, E, N, R, and T, were evaluated. All nine taccalonolides display microtubule stabilizing activity, but profound differences in antiproliferative potencies were noted, with IC50 values ranging from the low nanomolar range for taccalonolide AA (32 nM) to the low micromolar range for taccalonolide R (13 mu M). These studies demonstrate that diverse taccalonolides possess microtubule stabilizing properties and that significant structure-activity relationships exist. In vivo antitumor evaluations of taccalonolides A, E, and N show that each of these molecules has in vivo antitumor activity.
• Hydrolysis Reactions of the Taccalonolides Reveal Structure–Activity Relationships
  作者：Jing Li、Jiangnan Peng、April L. Risinger、Susan L. Mooberry

  DOI：10.1021/np400435t

  日期：2013.7.26

  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.