[(1S,2S,3R,4S,7S,8S,10R,13S)-4,10-diacetyloxy-4-(acetyloxymethyl)-13-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1-hydroxy-8,12,15,15-tetramethyl-7-methylsulfanylcarbothioyloxy-9-oxo-2-tricyclo[9.3.1.03,8]pentadec-11-enyl] benzoate | 344550-11-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(1S,2S,3R,4S,7S,8S,10R,13S)-4,10-diacetyloxy-4-(acetyloxymethyl)-13-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1-hydroxy-8,12,15,15-tetramethyl-7-methylsulfanylcarbothioyloxy-9-oxo-2-tricyclo[9.3.1.03,8]pentadec-11-enyl] benzoate
• CAS: 344550-11-4
• 化学式: C₅₇H₇₁NO₁₅S₂Si
• 分子量: 1102.41
• InChiKey: GTXZCMAJJCSJDJ-ROVZCLIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.99
• 重原子数：
  76
• 可旋转键数：
  23
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  274
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  [(1S,2S,3R,4S,7S,8S,10R,13S)-4,10-diacetyloxy-4-(acetyloxymethyl)-13-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1-hydroxy-8,12,15,15-tetramethyl-7-methylsulfanylcarbothioyloxy-9-oxo-2-tricyclo[9.3.1.03,8]pentadec-11-enyl] benzoate 在 偶氮二异丁腈 、 水 、 三正丁基氢锡 、 氟化氢吡啶 作用下， 以 吡啶 、 甲苯 为溶剂， 反应 4.0h， 生成 [(1S,2S,3R,4S,7S,8S,10R,13S)-4,10-diacetyloxy-4-(acetyloxymethyl)-13-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1,7-dihydroxy-8,12,15,15-tetramethyl-9-oxo-2-tricyclo[9.3.1.03,8]pentadec-11-enyl] benzoate
  参考文献：
  名称：

  Novel D-Seco Paclitaxel Analogues:  Synthesis, Biological Evaluation, and Model Testing

  摘要：

  Four new D-secopaclitaxel analogues were synthesized from paclitaxel. The key step of the synthesis involved the opening of the D-ring by Jones oxidation. Two of the compounds had been predicted to be nearly as active as paclitaxel in a minireceptor model of the binding site on tubulin, but all were biologically inactive in an in vitro cytotoxic assay and a tubulin assembly assay. The biological results identify a weakness in our predictive minireceptor model and suggest a corrective remedy in which additional amino acids are needed to accommodate ligand-protein steric effects around the oxetane ring. These changes to-the model lead to correct predictions of the bioactivity. Conformational analysis and dynamics simulations of the compounds showed that the 4-acetyl substituent is as important as the oxetane in determining the A ring conformation.

  DOI：

  10.1021/jo0015467
• 作为产物：
  描述：

  [(1S,2S,3R,4S,8S,10R,13S)-4,10-diacetyloxy-4-(acetyloxymethyl)-13-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1-hydroxy-8,12,15,15-tetramethyl-7,9-dioxo-2-tricyclo[9.3.1.03,8]pentadeca-5,11-dienyl] benzoate 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.75h， 生成 [(1S,2S,3R,4S,7S,8S,10R,13S)-4,10-diacetyloxy-4-(acetyloxymethyl)-13-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1-hydroxy-8,12,15,15-tetramethyl-7-methylsulfanylcarbothioyloxy-9-oxo-2-tricyclo[9.3.1.03,8]pentadec-11-enyl] benzoate
  参考文献：
  名称：

  Novel D-Seco Paclitaxel Analogues:  Synthesis, Biological Evaluation, and Model Testing

  摘要：

  Four new D-secopaclitaxel analogues were synthesized from paclitaxel. The key step of the synthesis involved the opening of the D-ring by Jones oxidation. Two of the compounds had been predicted to be nearly as active as paclitaxel in a minireceptor model of the binding site on tubulin, but all were biologically inactive in an in vitro cytotoxic assay and a tubulin assembly assay. The biological results identify a weakness in our predictive minireceptor model and suggest a corrective remedy in which additional amino acids are needed to accommodate ligand-protein steric effects around the oxetane ring. These changes to-the model lead to correct predictions of the bioactivity. Conformational analysis and dynamics simulations of the compounds showed that the 4-acetyl substituent is as important as the oxetane in determining the A ring conformation.

  DOI：

  10.1021/jo0015467