((2R,3R,4aS,5R,8S,8aS)-8-([1,1'-biphenyl]-4-ylmethoxy)-5-hydroxy-2,3-dimethoxy-2,3-dimethyl-2,3,4a,5,8,8a-hexahydrobenzo[b][1,4]dioxin-6-yl)methyl acetate | 1350450-05-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ((2R,3R,4aS,5R,8S,8aS)-8-([1,1'-biphenyl]-4-ylmethoxy)-5-hydroxy-2,3-dimethoxy-2,3-dimethyl-2,3,4a,5,8,8a-hexahydrobenzo[b][1,4]dioxin-6-yl)methyl acetate
• CAS: 1350450-05-3
• 化学式: C₂₈H₃₄O₈
• 分子量: 498.573
• InChiKey: SMCRQEZZRBZKJP-MUJQFDPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.61
• 重原子数：
  36.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  92.68
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ((2R,3R,4aS,5R,8S,8aS)-8-([1,1'-biphenyl]-4-ylmethoxy)-5-hydroxy-2,3-dimethoxy-2,3-dimethyl-2,3,4a,5,8,8a-hexahydrobenzo[b][1,4]dioxin-6-yl)methyl acetate 在 pyridinium dichromate 作用下， 生成 [(2R,3R,4aR,8S,8aS)-2,3-dimethoxy-2,3-dimethyl-5-oxo-8-[(4-phenylphenyl)methoxy]-8,8a-dihydro-4aH-1,4-benzodioxin-6-yl]methyl acetate
  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
• 作为产物：
  描述：

  4-溴甲基联苯 在 2,4,6-三甲基吡啶 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 ((2R,3R,4aS,5R,8S,8aS)-8-([1,1'-biphenyl]-4-ylmethoxy)-5-hydroxy-2,3-dimethoxy-2,3-dimethyl-2,3,4a,5,8,8a-hexahydrobenzo[b][1,4]dioxin-6-yl)methyl acetate
  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.