4-去氢醉茄素 A | 6850-30-2

• 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: 4-去氢醉茄素 A
• 中文别名: 4-去氢醉茄素A
• 英文名称: 4-dehydroxy-4-oxowithaferin A
• 英文别名: 4-dehydro-withaferin A；4-dehydrowithaferin A；(1S,2R,7S,9R,11S,12S,15R,16S)-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-ene-3,6-dione
• CAS: 6850-30-2
• 化学式: C₂₈H₃₆O₆
• 分子量: 468.59
• InChiKey: XGPALHIQWWGRFB-TTWUVOALSA-N

物化性质

• 溶解度：
  DMF：5 mg/ml；二甲基亚砜：5 mg/ml； DMSO:PBS (pH 7.2) (1:1)：0.5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  93.2
• 氢给体数：
  1
• 氢受体数：
  6

制备方法与用途

4-脱氢叶黄素A是一种类似于叶黄素A的化合物，而叶黄素A则是从叶黄素中提取出的一种叶黄素内酯。研究表明，4-脱氢血红蛋白A在研究多发性骨髓瘤方面具有潜在价值。

反应信息

• 作为反应物：
  描述：

  4-去氢醉茄素 A 在 吡啶 、 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.17h， 生成 27-acetyl-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
• 作为产物：
  描述：

  醉茄素 A 在 吡啶 、 咪唑 、 chromium(VI) oxide 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 27.08h， 生成 4-去氢醉茄素 A
  参考文献：
  名称：

  通过掺入硅来扩大Withaferin A的化学空间，以提高其在人卵巢癌细胞上的临床潜力。

  摘要：

  卵巢癌是全球第七大最常被诊断出的癌症。在此，我们报道了withaferin A（WA）-甲硅烷基醚文库的开发，该文库首次报道了30种类似物。对人上皮性卵巢癌顺铂敏感和耐药细胞系的细胞毒性试验鉴定出八种类似物，它们显示出纳摩尔效价（IC50为1至32 nM），高于先导化合物和参考药物。这种细胞毒性效力还与在非肿瘤细胞系上的良好选择性指数相结合。两种有效类似物的细胞周期分析显示，细胞凋亡通过细胞凋亡而没有表明细胞周期停滞在G0 / G1期。构效关系与计算机吸收，分布，代谢，排泄研究表明，WA框架中C-4处的硅和羰基基团的结合增强了效能，选择性和药物相似性。这些发现揭示了类似物22、23和25是复发性卵巢癌患者中临床翻译的潜在候选者。

  DOI：

  10.1021/acs.jmedchem.9b00146
• 作为试剂：
  描述：

  (1S,2R,6S,7R,9R,11S,12S,15R,16S)-6-hydroxy-15-[(1S)-1-[(2S)-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 在 manganese dioxide 4-去氢醉茄素 A 、 silica gel 作用下， 以 chloroform ethyl acetate 为溶剂， 反应 16.0h， 以to give 4-dehydrowithaferin A (18.4 mg, 62% yield)的产率得到4-去氢醉茄素 A
  参考文献：
  名称：

  WITHAFERIN A ANALOGS AND USES THEREOF

  摘要：

  本发明提供了一类新型的利用空气培养条件从印度人参（W. somnifera）中分离出来或半合成自天然产物的withanolides。本发明还提供了这些化合物的药物组合物以及在增生性疾病、神经退行性疾病、自身免疫和炎症性疾病中使用它们的方法。

  公开号：

  US20110230551A1

文献信息

• Withaferin A-related steroids from Withania aristata exhibit potent antiproliferative activity by inducing apoptosis in human tumor cells
  作者：Gabriel G. LLanos、Liliana M. Araujo、Ignacio A. Jiménez、Laila M. Moujir、Isabel L. Bazzocchi

  DOI：10.1016/j.ejmech.2012.05.032

  日期：2012.8

  Six new withanolides (1-6) along with eleven known ones (7-17) were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Semisynthesis of the minority metabolites 7 and 15 from compounds 6 and 9, respectively, as starting material, was performed. The isolated compounds as well as three derivatives (7a, 9a and 9b) of withaferin A were evaluated for cytotoxicity against HeLa (carcinoma of the cervix), A549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines, and against normal Vero cells (African green monkey kidney). Five compounds from this series (8, 9a, 9b, 11 and 13) exhibited potent antiproliferative effects on the tumor cells, even higher than the well known anticancer agent, withaferin A (9). Phosphatidylserine externalization, chromatin condensation, and caspase-3 activation clearly indicated apoptosis as a mechanism of action. The structure-activity relationship revealed valuable information on the pharmacophore for withanolide-type compounds. (C) 2012 Elsevier Masson SAS. All rights reserved.
• [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
• FUSKA, JAN;PROKSA, BUHUMIL;KHANDLOVA, ALZBETA;FUSKOVA, ALZBETA
  作者：FUSKA, JAN、PROKSA, BUHUMIL、KHANDLOVA, ALZBETA、FUSKOVA, ALZBETA

  DOI：——

  日期：——
• CN116082429
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.