[4-[(5R,5aR,8aR)-6-oxo-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]-2,6-dimethoxyphenyl] 2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetate | 1351047-43-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: [4-[(5R,5aR,8aR)-6-oxo-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]-2,6-dimethoxyphenyl] 2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetate
• CAS: 1351047-43-2
• 化学式: C₂₇H₂₃FN₂O₁₀
• 分子量: 554.485
• InChiKey: MIISEHCRIQHSQJ-SBQFXOPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4 ’-去甲去氧鬼臼毒素 、 2,4-二氧代-5-氟-3,4-二氢-1(2H)-嘧啶乙酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到[4-[(5R,5aR,8aR)-6-oxo-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]-2,6-dimethoxyphenyl] 2-(5-fluoro-2,4-dioxopyrimidin-1-yl)acetate
  参考文献：
  名称：

  Synthesis and biological evaluation of conjugates of deoxypodophyllotoxin and 5-FU as inducer of caspase-3 and -7

  摘要：

  In order to generate compounds with superior antitumor activity and reduced toxicity, a series of conjugates of deoxypodophyllotoxin and 5-FU were synthesized by coupling 4'-demethyl-4-dexoypodophyllotoxin with N-(5-fluorouracil-N-1-ly acetic)- amino acids (or 5-fluorouracil-N-1-ly acetic acid). The cytotoxic activity of these compounds against four human cancer cell lines (HL-60, A-549, HeLa and SiHa) were evaluated, and results indicated that these compounds were more potent in terms of cytotoxicity than either parent compound DPT or anticancer drug VP-16 and 5-FU. In addition, we found that 14d induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells, and 14d activated caspase-3 and -7. These results suggested that caspase-mediated pathways are involved in 14d induced apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.12.005

文献信息

• Synthesis and biological evaluation of conjugates of deoxypodophyllotoxin and 5-FU as inducer of caspase-3 and -7
  作者：Wen-Ting Huang、Jie Liu、Jian-Fei Liu、Ling Hui、Yi-Lan Ding、Shi-Wu Chen

  DOI：10.1016/j.ejmech.2011.12.005

  日期：2012.3

  In order to generate compounds with superior antitumor activity and reduced toxicity, a series of conjugates of deoxypodophyllotoxin and 5-FU were synthesized by coupling 4'-demethyl-4-dexoypodophyllotoxin with N-(5-fluorouracil-N-1-ly acetic)- amino acids (or 5-fluorouracil-N-1-ly acetic acid). The cytotoxic activity of these compounds against four human cancer cell lines (HL-60, A-549, HeLa and SiHa) were evaluated, and results indicated that these compounds were more potent in terms of cytotoxicity than either parent compound DPT or anticancer drug VP-16 and 5-FU. In addition, we found that 14d induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells, and 14d activated caspase-3 and -7. These results suggested that caspase-mediated pathways are involved in 14d induced apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.