dimethyl 3-[[(1S,4aR,5S,8aR)-5-methoxycarbonyl-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]methyl]-4-methylbenzene-1,2-dicarboxylate | 1131892-10-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: dimethyl 3-[[(1S,4aR,5S,8aR)-5-methoxycarbonyl-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]methyl]-4-methylbenzene-1,2-dicarboxylate
• CAS: 1131892-10-8
• 化学式: C₂₇H₃₆O₆
• 分子量: 456.579
• InChiKey: VGOAFNSSVQGWPL-BEYVDOMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (E)-methyl communate 、 丁炔二酸二甲酯 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 1,4-二氧六环 为溶剂， 反应 6.0h， 以95%的产率得到dimethyl 3-[[(1S,4aR,5S,8aR)-5-methoxycarbonyl-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]methyl]-4-methylbenzene-1,2-dicarboxylate
  参考文献：
  名称：

  Novel merosesquiterpene exerts a potent antitumor activity against breast cancer cells in vitro and in vivo

  摘要：

  This article describes the antitumor properties of a new family of merosesquiterpenes, which were synthesized by Diels-Alder cycloaddition of the labdane diene trans-communic acid, highly abundant in Cupressus sempervirens, or its methyl ester, with the appropriate dienophile. These compounds demonstrated potent cytotoxic activity in vitro against human breast, colon, and lung tumor cells. We highlight the elevated activity (IC50: 0.35 +/- 0.10 mu M) and specificity (TI: 9) of compound 13 against the MCF-7 line, which corresponds to the most prevalent breast cancer cell subtype, luminal A. It was found that compound 13 exerts its anti-tumor action by inducing oxidative stress, arresting the cell cycle in stages G(0)-G(1), and activating apoptosis, which are all associated with low cyclin D1 regulation, pRb hypophosphorylation, increased expression of p27 and p53, and poly (ADP-ribose) polymerase (PARP) fractioning. Epithelial-mesenchymal transition, a phenomenon associated with metastasis promotion and a worsened prognosis also appeared to be inhibited by compound 13. In addition, it markedly reduced tumor development in immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells (luminal A subtype). According to these findings, this new family of compounds, especially compound 13, may be highly useful in the treatment of human breast cancer. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.071