睡茄素A | 32911-62-9

• 物质功能分类: 分析化学 - 分析试剂 - 离子色谱试剂
• 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: 睡茄素A
• 英文名称: withanolide A
• 英文别名: 5α,20α_F(R)-dihydroxy-6α,7α-epoxy-1-oxowitha-2,24-dienolide；(1S,2S,4S,5R,10R,11S,14S,15S,18S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-5-hydroxy-10,14-dimethyl-3-oxapentacyclo[9.7.0.02,4.05,10.014,18]octadec-7-en-9-one
• CAS: 32911-62-9
• 化学式: C₂₈H₃₈O₆
• 分子量: 470.606
• InChiKey: DXWHOKCXBGLTMQ-SFQAJKIESA-N

物化性质

• 熔点：
  305℃ (DEC.)
• 沸点：
  651.6±55.0 °C(Predicted)
• 密度：
  1.264
• 溶解度：
  在甲醇中可溶1mg/mL，透明，无色

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  96.4
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• WGK Germany：
  3
• 海关编码：
  2932206000

制备方法与用途

生物活性方面，Withanolide A 可从印度草药阿育伍德（Ashwagandha）中提取。在受损严重的神经元中，它能够促进神经元轴突再生，并帮助重建突触连接。

反应信息

• 作为反应物：
  描述：

  睡茄素A 在 叔丁基过氧化氢 、 重铬酸吡啶 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 溶剂黄146 、 肼 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.33h， 生成 withanolide A
  参考文献：
  名称：

  Profiling withanolide A for therapeutic targets in neurodegenerative diseases

  摘要：

  To identify new potential therapeutic targets for neurodegenerative diseases, we initiated activity-based protein profiling studies with withanolide A (WitA), a known neuritogenic constituent of Withania somnifera root with unknown mechanism of action. Molecular probes were designed and synthesized, and led to the discovery of the glucocorticoid receptor (GR) as potential target. Molecular modeling calculations using the VirtualToxLab predicted a weak binding affinity of WitA for GR. Neurite outgrowth experiments in human neuroblastoma SH-SY5Y cells further supported a glucocorticoid-dependent mechanism, finding that WitA was able to reverse the outgrowth inhibition mediated by dexamethasone (Dex). However, further GR binding and transactivation assays found no direct interference of WitA. Further molecular modeling analysis suggested that WitA, although forming several contacts with residues in the GR binding pocket, is lacking key stabilizing interactions as observed for Dex. Taken together, the data suggest that WitA-dependent induction of neurite outgrowth is not through a direct effect on GR, but might be mediated through a closely related pathway. Further experiments should evaluate a possible role of GR modulators and/or related signaling pathways such as ERK, Akt, NF-kappa B, TR alpha, or Hsp90 as potential targets in the WitA-mediated neuromodulatory effects.

  DOI：

  10.1016/j.bmc.2019.03.022
• 作为产物：
  描述：

  withacoagin 在 titanium(IV) isopropylate 、 叔丁基过氧化氢 作用下， 以 氯仿 、 癸烷 为溶剂， 以70 %的产率得到睡茄素A
  参考文献：
  名称：

  [EN] PROCESSES FOR SYNTHESIS OF WITHANOLIDES AND WITHAFERINS AND ANALOGS THEREOF
  [FR] PROCÉDÉS DE SYNTHÈSE DE WITHANOLIDES ET DE WITHAFÉRINES ET D'ANALOGUES DE CEUX-CI

  摘要：

  The present disclosure provides processes for the synthesis of withanolides such as Withanolide A and Withanolide D.

  公开号：

  WO2023172499A2

文献信息

• Withanolide A: synthesis and structural requirements for neurite outgrowth
  作者：Raphael Liffert、Johannes Hoecker、Chandan K. Jana、Tom M. Woods、Patrick Burch、Henning J. Jessen、Markus Neuburger、Karl Gademann

  DOI：10.1039/c3sc50653c

  日期：——

  The exploration of different routes leading to the stereoselective synthesis of the neuritogenic steroid withanolide A is reported in full detail. Notable features of the synthesis include a Corey–Seebach homologation, a vinylogous aldol reaction, a singlet oxygen Schenck-ene reaction, and finally, a late-stage Wharton transposition. Semi-synthetic elaboration of the natural product resulted in 15

  详细报道了探索各种途径导致立体选择性合成神经生成类固醇withanolide A的方法。合成的显着特征包括Corey–Seebach同源性，乙烯基醇醛醇醛反应，单重态氧Schenck-ene反应以及最后的沃顿换位反应。天然产物的半合成工艺产生了15种衍生物，可以更好地了解其固有的反应模式以及与神经元分化和神经突生长有关的生物学特性。
• Synthesis of Withanolide A, Biological Evaluation of Its Neuritogenic Properties, and Studies on Secretase Inhibition
  作者：Chandan Kumar Jana、Johannes Hoecker、Tom M. Woods、Henning J. Jessen、Markus Neuburger、Karl Gademann

  DOI：10.1002/anie.201101869

  日期：2011.8.29

  Neurons on steroids: A stereoselective synthesis of the neuritogenic steroid lactone withanolide A was achieved by singlet oxygen ene reaction, Wharton transposition, a Corey–Seebach homologation, and a vinylogous aldol reaction. Biological evaluation demonstrated neurite outgrowth, which supports the potential neuritogenic role of this compound in traditional Indian medicine.

  类固醇上的神经元：通过单线态氧烯反应，沃顿换位，Corey-Seebach同源性和乙烯基醛醇缩合反应，实现了神经生成类固醇内酯与醇化物A的立体选择性合成。生物学评估表明神经突向外生长，这支持了该化合物在传统印度医学中的潜在神经发生作用。
• Epoxide group relationship with cytotoxicity in withanolide derivatives from Withania somnifera
  作者：Pallavi Joshi、Laxminarain Misra、Amreen A. Siddique、Monica Srivastava、Shiv Kumar、Mahendra P. Darokar

  DOI：10.1016/j.steroids.2013.10.008

  日期：2014.1

  Withania somnifera is one of the highly reputed medicinal plants of India. Its steroidal constituents exist in the form of two major substitution patterns, viz. withaferin A (1) and withanone (5). Withaferin A with oxidation at carbons 4, 5, and 6 is considered as an active type, especially as anticancer, whereas the withanones with oxidation at carbons 5, 6, and 7 rarely show any activity. We prepared

  Withania somnifera 是印度著名的药用植物之一。其甾体成分以两种主要替代模式的形式存在，即。withaferin A (1) 和 withanone (5)。在碳 4、5 和 6 处氧化的睡茄素 A 被认为是一种活性类型，尤其是具有抗癌作用，而在碳 5、6 和 7 处氧化的睡茄酮很少显示出任何活性。我们制备了一系列在这些 withanolides 的环 B 中的碳 5、6 和 7 处进行修饰的衍生物，以研究环氧基对这些生物活性类固醇的细胞毒性的作用。我们已经将 withanolides 转化为相应的硫杂丙烷，氨基醇和醇通过在环氧化物环上的选择性反应，并评估了对四种癌细胞系的体外抗癌活性，以研究结构活性关系。withaferin A 型的 withanolides 中环氧基的转化显示出其细胞毒性的适度降低，而几乎无活性的 withanones 在其醇衍生物中显示出一些改善。
• NEOGI, PARTHA;KAWAI, MASAO;BUTSUGAN, YASUO;MORI, YUJI;SUZUKI, MAKOTO, BULL. CHEM. SOC. JAP., 61,(1988) N2, C. 4479-4481
  作者：NEOGI, PARTHA、KAWAI, MASAO、BUTSUGAN, YASUO、MORI, YUJI、SUZUKI, MAKOTO

  DOI：——

  日期：——
• Withanolides from Withania somnifera roots
  作者：Laxminarain Misra、Priyanka Mishra、Archana Pandey、Rajender S. Sangwan、Neelam S. Sangwan、Rakesh Tuli

  DOI：10.1016/j.phytochem.2007.10.024

  日期：2008.2

  Two new and seven known withanolides along with beta-sitosterol, stigniasterol, beta-sitosterol glucoside, stigniasterol glucoside, alpha + beta glucose were isolated from the roots of Withania somnifera. Among the known compounds, Viscosa lactone B, stigmasterol, stigmasterol glucoside and alpha + beta glucose are being reported from the roots of W. somnifera for the first time. One of the new compounds contained the rare 16 beta-acetoxy-17(20)-ene the other contained unusual 6 alpha-hydroxy-5,7 alpha-epoxy functional groups in the withasteroid skeleton. The structures were elucidated by spectroscopic methods and chemical transformations. (C) 2007 Elsevier Ltd. All rights reserved.