(6S,6aS,8R,9R,10aS,10bR)-8,9-dimethoxy-2,2,8,9-tetramethyl-6-(naphthalen-2-ylmethoxy)-6,6a,10a,10b-tetrahydro-4H-[1,4]dioxino[2,3-h][1,3]benzodioxine | 1350449-86-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (6S,6aS,8R,9R,10aS,10bR)-8,9-dimethoxy-2,2,8,9-tetramethyl-6-(naphthalen-2-ylmethoxy)-6,6a,10a,10b-tetrahydro-4H-[1,4]dioxino[2,3-h][1,3]benzodioxine
• CAS: 1350449-86-3
• 化学式: C₂₇H₃₄O₇
• 分子量: 470.563
• InChiKey: ZOJJLAGKWSDLDY-QNLCIIDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (6S,6aS,8R,9R,10aS,10bR)-8,9-dimethoxy-2,2,8,9-tetramethyl-6-(naphthalen-2-ylmethoxy)-6,6a,10a,10b-tetrahydro-4H-[1,4]dioxino[2,3-h][1,3]benzodioxine 在 2,4,6-三甲基吡啶 、 重铬酸吡啶 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 7.0h， 生成
  参考文献：
  名称：

  Inhibition of Glutathione S-Transferase M1 by New Gabosine Analogues Is Essential for Overcoming Cisplatin Resistance in Lung Cancer Cells

  摘要：

  A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.

  DOI：

  10.1021/jm201131n
• 作为产物：
  描述：

  (1S,2S,3S,4R)-2,3-[(2R,3R)-2,3-dimethoxybutan-2,3-dioxy]-5-hydroxymethyl-4,6-di-O-isopropylidene-5-cyclohexene-1,2,3,4-tetraol 、 2-溴甲基萘 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 (6S,6aS,8R,9R,10aS,10bR)-8,9-dimethoxy-2,2,8,9-tetramethyl-6-(naphthalen-2-ylmethoxy)-6,6a,10a,10b-tetrahydro-4H-[1,4]dioxino[2,3-h][1,3]benzodioxine
  参考文献：
  名称：

  Synthesis of chiral hydroxylated enones as potential anti-tumor agents

  摘要：

  A series of chiral hydroxylated enones were synthesized as COTC ether analogues to investigate the structural features required for optimal and selective anti-tumor activity. The cytotoxicity of the seven COTC ether analogues against WRL-68 normal and HepG2, HL-60 cancer cell lines were measured. C-4 ether analogues with an aliphatic chain substituent were found to be more favorable than their aromatic counterparts. Inversion of the configuration at C-4 in 5e to give 5f only resulted in reduced selectivity towards cancer cells. These results show that 4-O-pentyl-gabosine D (5e) has optimum selectivity and cytotoxicity towards two cancer cell lines. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.026

文献信息

• Inhibition of Glutathione <i>S</i>-Transferase M1 by New Gabosine Analogues Is Essential for Overcoming Cisplatin Resistance in Lung Cancer Cells
  作者：Chie-Hong Wang、Ho T. Wu、Hau M. Cheng、Tien-Jui Yen、I-Hsuan Lu、Hui Chuan Chang、Shu-Chuan Jao、Tony K. M. Shing、Wen-Shan Li

  DOI：10.1021/jm201131n

  日期：2011.12.22

  A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.
• Synthesis of chiral hydroxylated enones as potential anti-tumor agents
  作者：Tony K.M. Shing、Ho T. Wu、H.F. Kwok、Clara B.S. Lau

  DOI：10.1016/j.bmcl.2012.10.026

  日期：2012.12

  A series of chiral hydroxylated enones were synthesized as COTC ether analogues to investigate the structural features required for optimal and selective anti-tumor activity. The cytotoxicity of the seven COTC ether analogues against WRL-68 normal and HepG2, HL-60 cancer cell lines were measured. C-4 ether analogues with an aliphatic chain substituent were found to be more favorable than their aromatic counterparts. Inversion of the configuration at C-4 in 5e to give 5f only resulted in reduced selectivity towards cancer cells. These results show that 4-O-pentyl-gabosine D (5e) has optimum selectivity and cytotoxicity towards two cancer cell lines. (c) 2012 Elsevier Ltd. All rights reserved.