4-epi-withaferin A | 1214886-27-7

• 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: 4-epi-withaferin A
• 英文别名: 4-epi-Withaferin A；(1S,2R,6R,7R,9R,11S,12S,15R,16S)-6-hydroxy-15-[(1S)-1-[(2R)-5-(hydroxymethyl)-4-methyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one
• CAS: 1214886-27-7
• 化学式: C₂₈H₃₈O₆
• 分子量: 470.606
• InChiKey: DBRXOUCRJQVYJQ-SKXGSRCNSA-N

物化性质

• 熔点：
  227-228 °C
• 沸点：
  680.7±55.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  3
• 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

制备方法与用途

4-epi-Withaferin A（化合物28）是Withaferin A的类似物，能够增强细胞毒性并提高热休克诱导活性（HSA）。这种化合物有可能通过激活细胞防御机制来研究与蛋白质聚集相关的疾病。

反应信息

• 作为反应物：
  描述：

  4-epi-withaferin A 、 乙酸酐 在 吡啶 作用下， 反应 14.0h， 以93%的产率得到4,27-di-O-acetyl-4-epi-withaferin A
  参考文献：
  名称：

  [EN] WITHAFERIN A ANALOGS AND USES THEREOF
  [FR] ANALOGUES DE LA WITHAFÉRINE A ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2010030395A3
• 作为产物：
  描述：

  醉茄素 A 在 manganese(IV) oxide 、 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 16.5h， 生成 4-epi-withaferin A
  参考文献：
  名称：

  Structure–Activity Relationships for Withanolides as Inducers of the Cellular Heat-Shock Response

  摘要：

  To understand the relationship between the structure and the remarkably diverse bioactivities reported for withanolides, we obtained withaferin A (WA; 1) and 36 analogues (2-37) and compared their cytotoxicity to cytoprotective heat-shock-inducing activity (HSA). By analyzing structure activity relationships for the series, we found that the ring A enone is essential for both bioactivities. Acetylation of 27-OH of 4-epi-WA (28) to 33 enhanced both activities, whereas introduction of beta-OH to WA at C-12 (29) and C-15 (30) decreased both activities. Introduction of beta-OAc to 4,4,27-diacetyl-WA (16) at C-15 (37) decreased HSA without affecting cytotoxicity, but at C-12 (36), it had minimal effect. Importantly, acetylation of 27-OH, yielding 15 from 1, 16 from 14, and 35 from 34, enhanced HSA without increasing cytotoxicity. Our findings demonstrate that the withanolide scaffold can be modified to enhance HSA selectively, thereby assisting development of natural product-inspired drugs to combat protein aggregation-associated diseases by stimulating cellular defense mechanisms.

  DOI：

  10.1021/jm401279n

文献信息

• Structure–Activity Relationships for Withanolides as Inducers of the Cellular Heat-Shock Response
  作者：E. M. Kithsiri Wijeratne、Ya-Ming Xu、Ruth Scherz-Shouval、Marilyn T. Marron、Danilo D. Rocha、Manping X. Liu、Leticia V. Costa-Lotufo、Sandro Santagata、Susan Lindquist、Luke Whitesell、A. A. Leslie Gunatilaka

  DOI：10.1021/jm401279n

  日期：2014.4.10

  To understand the relationship between the structure and the remarkably diverse bioactivities reported for withanolides, we obtained withaferin A (WA; 1) and 36 analogues (2-37) and compared their cytotoxicity to cytoprotective heat-shock-inducing activity (HSA). By analyzing structure activity relationships for the series, we found that the ring A enone is essential for both bioactivities. Acetylation of 27-OH of 4-epi-WA (28) to 33 enhanced both activities, whereas introduction of beta-OH to WA at C-12 (29) and C-15 (30) decreased both activities. Introduction of beta-OAc to 4,4,27-diacetyl-WA (16) at C-15 (37) decreased HSA without affecting cytotoxicity, but at C-12 (36), it had minimal effect. Importantly, acetylation of 27-OH, yielding 15 from 1, 16 from 14, and 35 from 34, enhanced HSA without increasing cytotoxicity. Our findings demonstrate that the withanolide scaffold can be modified to enhance HSA selectively, thereby assisting development of natural product-inspired drugs to combat protein aggregation-associated diseases by stimulating cellular defense mechanisms.
• [EN] WITHAFERIN A ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES DE LA WITHAFÉRINE A ET LEURS UTILISATIONS
  申请人：WHITEHEAD BIOMEDICAL INST

  公开号：WO2010030395A3

  公开（公告）日：2010-07-01