(2R,4aR,6R,7R,8R,8aS)-6-[(5S,5aR,8aR,9R)-9-(4-Hydroxy-3,5-dimethoxy-phenyl)-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yloxy]-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxine-7,8-diol

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基四氢萘木脂素
• 英文名称: (2R,4aR,6R,7R,8R,8aS)-6-[(5S,5aR,8aR,9R)-9-(4-Hydroxy-3,5-dimethoxy-phenyl)-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yloxy]-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxine-7,8-diol
• 英文别名: (2R,4aR,6R,7R,8R,8aS)-6-[[(5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,6,8,8a,9-hexahydro-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]oxy]-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxine-7,8-diol
• 化学式: C₂₉H₃₄O₁₂
• 分子量: 574.582
• InChiKey: HEOGDJBBJQBUSY-URLMKTSKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  144
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  依托泊苷 在 吡啶 、 lithium aluminium tetrahydride 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 80.5h， 生成 (2R,4aR,6R,7R,8R,8aS)-6-[(5S,5aR,8aR,9R)-9-(4-Hydroxy-3,5-dimethoxy-phenyl)-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yloxy]-2-methyl-hexahydro-pyrano[3,2-d][1,3]dioxine-7,8-diol
  参考文献：
  名称：

  Synthesis, 470-MHz proton NMR spectra, and activity of delactonized derivatives of the anticancer drug etoposide

  摘要：

  The anticancer drug etoposide (VP 16-213, 1) contains a highly strained trans-fused gamma-lactone. This functionality is readily metabolized to an inactive ring-opened hydroxy acid (2). To prevent this detoxification of the drug and to investigate whether the lactone is essential for drug activity, we synthesized a cyclic ether analogue of etoposide (3) and tested it in the mouse leukemia L1210 system in vitro and in vivo. This ether analogue of etoposide was found to retain activity in the L1210 system, but the activity was reduced relative to the parent drug. A synthetic intermediate, the ring D opened diol of the reduced lactone (4), was also tested and found to be inactive in the L1210 system. The complete 470-MHz 1H NMR spectra of etoposide and its derivatives are reported. The usefulness of introducing deuterium at C-13 to determine J2,3 is also demonstrated. This coupling constant is characteristic of cis or trans stereochemistry across the C-D ring fusion.

  DOI：

  10.1021/jm00351a014

文献信息

• Synthesis, 470-MHz proton NMR spectra, and activity of delactonized derivatives of the anticancer drug etoposide
  作者：Ian Jardine、Robert J. Strife、John Kozlowski

  DOI：10.1021/jm00351a014

  日期：1982.9

  The anticancer drug etoposide (VP 16-213, 1) contains a highly strained trans-fused gamma-lactone. This functionality is readily metabolized to an inactive ring-opened hydroxy acid (2). To prevent this detoxification of the drug and to investigate whether the lactone is essential for drug activity, we synthesized a cyclic ether analogue of etoposide (3) and tested it in the mouse leukemia L1210 system in vitro and in vivo. This ether analogue of etoposide was found to retain activity in the L1210 system, but the activity was reduced relative to the parent drug. A synthetic intermediate, the ring D opened diol of the reduced lactone (4), was also tested and found to be inactive in the L1210 system. The complete 470-MHz 1H NMR spectra of etoposide and its derivatives are reported. The usefulness of introducing deuterium at C-13 to determine J2,3 is also demonstrated. This coupling constant is characteristic of cis or trans stereochemistry across the C-D ring fusion.