(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 | 1334232-69-7

• 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: (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
• 英文别名: (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-8-en-7-one
• CAS: 1334232-69-7
• 化学式: C₂₈H₃₈O₆
• 分子量: 470.606
• InChiKey: ZPRPJVFTCBONSM-FKKDDYPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 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

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  withanolide A 在 4-甲氧基吡啶-N-氧化物 、 2-碘酰基苯甲酸 作用下， 以 二甲基亚砜 为溶剂， 反应 120.0h， 生成 (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
  参考文献：
  名称：

  Withanolide A的合成，其神经营养特性的生物学评估以及分泌酶抑制作用的研究

  摘要：

  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。

  DOI：

  10.1002/anie.201101869

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。