withanolide A | 1334232-74-4

• 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: withanolide A
• CAS: 1334232-74-4
• 化学式: C₂₈H₄₀O₆
• 分子量: 472.622
• InChiKey: AJPVNXJXVACGJG-FKKDDYPESA-N

物化性质

• 沸点：
  642.2±55.0 °C(predicted)
• 密度：
  1.247±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.72
• 重原子数：
  34.0
• 可旋转键数：
  2.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  96.36
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  withanolide A 在 2-iodoxybenzoic acid 、 双氧水 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  Withanolide A：神经突增生的合成和结构要求†

  摘要：

  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。

  DOI：

  10.1039/c3sc50653c
• 作为产物：
  描述：

  (4aR,4bS,6aS,7S,9aS,9bS,9cS,10aS,10bR)-7-((R)-1-((R)-4,5-dimethyl-6-oxo-3,6-dihydro-2H-pyran-2-yl)-1-hydroxyethyl)-10b-hydroxy-4a,6a-dimethyl-1,4a,4b,5,6,6a,7,8,9,9a,9b,9c,10a,10b-tetradecahydro-2H-cyclopenta[1,2]phenanthro[9,10-b]oxiren-2-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 以80%的产率得到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

文献信息

• 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。