[(1R,2S,10R,12R,13S)-5-acetyloxy-12-cyano-8-hydroxy-7,18-dimethoxy-6,17,21-trimethyl-16,19-dioxo-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),17-pentaen-10-yl]methyl (Z)-2-methylbut-2-enoate | 1448222-72-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: [(1R,2S,10R,12R,13S)-5-acetyloxy-12-cyano-8-hydroxy-7,18-dimethoxy-6,17,21-trimethyl-16,19-dioxo-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),17-pentaen-10-yl]methyl (Z)-2-methylbut-2-enoate
• CAS: 1448222-72-7
• 化学式: C₃₃H₃₇N₃O₉
• 分子量: 619.671
• InChiKey: PGAZIESKLVICSW-RWLCNBJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  renieramycin M 在 吡啶 、 palladium on carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 17.0h， 生成 [(1R,2S,10R,12R,13S)-5,8-diacetyloxy-12-cyano-7,18-dimethoxy-6,17,21-trimethyl-16,19-dioxo-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),17-pentaen-10-yl]methyl (Z)-2-methylbut-2-enoate 、 [(1R,2S,10R,12R,13S)-5-acetyloxy-12-cyano-8-hydroxy-7,18-dimethoxy-6,17,21-trimethyl-16,19-dioxo-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4(9),5,7,15(20),17-pentaen-10-yl]methyl (Z)-2-methylbut-2-enoate
  参考文献：
  名称：

  雷尼霉素的化学。17.新一代的雷尼霉素：雷尼霉素M的氢醌5- O-单酯类似物作为针对非小细胞肺癌细胞的潜在细胞毒剂

  摘要：

  通过双氢醌肾上腺素霉素M（5），从肾上腺素M（1）（从泰国蓝色海绵Xestospongia sp。分离出的一种主要的细胞毒性双四氢异喹啉啉醌生物碱）中制备的双氢醌肾上腺素M（5），半合成肾上腺素M的一系列氢醌5- O-单酯类似物。所有20种对苯二酚5- O-单酯类似物均具有针对H292和H460人非小细胞肺癌（NSCLC）细胞系的纳摩尔浓度IC 50值的细胞毒性。从5- O-单酯类似物如5- O-乙酰基酯6a和5- O观察到对NSCLC细胞系的改善的细胞毒性。-丙酸酯7e，相对于1（IC 50 24 nM），对H292 NSCLC细胞系的细胞毒性增加了8倍和10倍（分别为IC 50 3.0和2.3 nM）。因此，对苯二酚5- O-单酯类似物是新一代的雷尼霉素，将被进一步开发为潜在的海洋来源的肺癌候选药物。

  DOI：

  10.1021/acs.jnatprod.7b00068

文献信息

• Replacement of a Quinone by a 5-<i>O</i>-Acetylhydroquinone Abolishes the Accidental Necrosis Inducing Effect while Preserving the Apoptosis-Inducing Effect of Renieramycin M on Lung Cancer Cells
  作者：Thaniwan Cheun-Arom、Pithi Chanvorachote、Natchanun Sirimangkalakitti、Taksina Chuanasa、Naoki Saito、Ikuro Abe、Khanit Suwanborirux

  DOI：10.1021/np400277m

  日期：2013.8.23

  Renieramycin M (1), a bistetrahydroisoquinolinequinone alkaloid isolated from the marine sponge Xestospongia sp., has been reported to possess promising anticancer effects. However, its accidental necrosis inducing effect has limited further development due to concerns of unwanted toxicity. The presence of two quinone moieties in its structure was demonstrated to induce accidental necrosis and increase reactive oxygen species (ROS) levels. Therefore, one quinone of 1 was modified to produce the 5-O-acetylated hydroquinone derivative (2), and 2 dramatically reduced the accidental necrosis inducing effect while preserving the apoptosis-inducing effect of parent 1 on lung cancer H23 cells. Addition of the antioxidant N-acetylcysteine suppressed the accidental necrosis mediated by 1, suggesting that its accidental necrosis inducing effect was ROS-dependent. The fluorescent probe dihydroethidium revealed that the accidental necrosis mediated by 1 was due to its ability to generate intracellular superoxide anions. Interestingly, the remaining quinone in 2 was required for its cytotoxicity, as the 5,8,15,18-O-tetraacetylated bishydroquinone derivative (3) exhibited weak cytotoxicity compared to 1 and 2. The present study demonstrates a simple way to eliminate the undesired accidental necrosis inducing effect of substances that may be developed as improved anticancer drug candidates.
• Chemistry of Renieramycins. 17. A New Generation of Renieramycins: Hydroquinone 5-<i>O</i>-Monoester Analogues of Renieramycin M as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells
  作者：Supakarn Chamni、Natchanun Sirimangkalakitti、Pithi Chanvorachote、Naoki Saito、Khanit Suwanborirux

  DOI：10.1021/acs.jnatprod.7b00068

  日期：2017.5.26

  A series of hydroquinone 5-O-monoester analogues of renieramycin M were semisynthesized via bishydroquinonerenieramycin M (5) prepared from renieramycin M (1), a major cytotoxic bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. All 20 hydroquinone 5-O-monoester analogues possessed cytotoxicity with IC50 values in nanomolar concentrations against the H292

  通过双氢醌肾上腺素霉素M（5），从肾上腺素M（1）（从泰国蓝色海绵Xestospongia sp。分离出的一种主要的细胞毒性双四氢异喹啉啉醌生物碱）中制备的双氢醌肾上腺素M（5），半合成肾上腺素M的一系列氢醌5- O-单酯类似物。所有20种对苯二酚5- O-单酯类似物均具有针对H292和H460人非小细胞肺癌（NSCLC）细胞系的纳摩尔浓度IC 50值的细胞毒性。从5- O-单酯类似物如5- O-乙酰基酯6a和5- O观察到对NSCLC细胞系的改善的细胞毒性。-丙酸酯7e，相对于1（IC 50 24 nM），对H292 NSCLC细胞系的细胞毒性增加了8倍和10倍（分别为IC 50 3.0和2.3 nM）。因此，对苯二酚5- O-单酯类似物是新一代的雷尼霉素，将被进一步开发为潜在的海洋来源的肺癌候选药物。