withalongolide A 4,19,27-triacetate | 1349894-28-5

• 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: withalongolide A 4,19,27-triacetate
• 英文别名: (4S,20S,22R)-4β,19,27-triacetyloxy-5β,6β-epoxy-1-oxowitha-2,24-dienolide；Withalongolide A 4,19,27-Triacetae；[(2R)-2-[(1S)-1-[(1S,2S,6S,7S,9R,11S,12S,15R,16S)-6-acetyloxy-2-(acetyloxymethyl)-16-methyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-15-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate
• CAS: 1349894-28-5
• 化学式: C₃₄H₄₄O₁₀
• 分子量: 612.717
• InChiKey: KSMCZEDDTUJWBE-QSRYYZERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  withalongolide A 4,19,27-triacetate 在 4-二甲氨基吡啶 、 碘 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以71%的产率得到(4S,20S,22R)-2-iodo-4β,19,27-triacetyloxy-5β,6β-epoxy-1-oxowitha-2,24-dienolide
  参考文献：
  名称：

  Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues

  摘要：

  The natural product withaferin A exhibits potent antitumor activity and other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was recently reported to possess cytotoxic activity against head and neck squamous cell carcinomas. Semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure activity relationships, 20 new semisynthetic analogues of withalongolide A were synthesized and evaluated for cytotoxic activity against four different cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A.

  DOI：

  10.1021/ml400267q
• 作为产物：
  描述：

  withalongolide A 、 乙酸酐 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 2.0h， 以99%的产率得到withalongolide A 4,19,27-triacetate
  参考文献：
  名称：

  Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues

  摘要：

  The natural product withaferin A exhibits potent antitumor activity and other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was recently reported to possess cytotoxic activity against head and neck squamous cell carcinomas. Semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure activity relationships, 20 new semisynthetic analogues of withalongolide A were synthesized and evaluated for cytotoxic activity against four different cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A.

  DOI：

  10.1021/ml400267q

文献信息

• Cytotoxic Withanolide Constituents of <i>Physalis longifolia</i>
  作者：Huaping Zhang、Abbas K. Samadi、Robert J. Gallagher、Juan J. Araya、Xiaoqin Tong、Victor W. Day、Mark S. Cohen、Kelly Kindscher、Rao Gollapudi、Barbara N. Timmermann

  DOI：10.1021/np200635r

  日期：2011.12.27

  Fourteen new withanolides, 1–14, named withalongolides A–N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15–22). The structures of compounds 1–14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS

  从Physalis longifolia的地上部分分离出 14 种新的睡茄内酯1 – 14 ，分别命名为 withalongolides A–N 以及八种已知化合物 ( 15 – 22 )。通过光谱技术和化学方法阐明了化合物1-14的结构。另外，睡茄内酯1、2、3和6的结构通过X射线晶体分析得到确认。使用MTS活力测定，八种茄内酯（ 1 , 2 , 3 , 7 , 8 , 15 , 16 , 和19 ）和四种乙酰化衍生物（ 1a , 1b , 2a , 和2b ）对人头颈鳞状细胞显示出有效的细胞毒性癌（JMAR 和 MDA-1986）、黑色素瘤（B16F10 和 SKMEL-28）和正常胎儿成纤维细胞 (MRC-5) 细胞，IC 50值在 0.067 至 9.3 μM 之间。