[(1S,2S,4R,8S,9R,10S,11S,15S)-11-acetyloxy-8-(acetyloxymethyl)-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-10,14,17,17-tetramethyl-6,12-dioxo-3,7-dioxatetracyclo[11.3.1.02,9.04,8]heptadec-13-en-1-yl] benzoate | 344550-00-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(1S,2S,4R,8S,9R,10S,11S,15S)-11-acetyloxy-8-(acetyloxymethyl)-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-10,14,17,17-tetramethyl-6,12-dioxo-3,7-dioxatetracyclo[11.3.1.02,9.04,8]heptadec-13-en-1-yl] benzoate
• CAS: 344550-00-1
• 化学式: C₅₃H₆₃NO₁₄Si
• 分子量: 966.167
• InChiKey: HGEJKHGZECIBPN-IEBSWRQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.59
• 重原子数：
  69
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  196
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  [(1S,2S,4R,8S,9R,10S,11S,15S)-11-acetyloxy-8-(acetyloxymethyl)-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-10,14,17,17-tetramethyl-6,12-dioxo-3,7-dioxatetracyclo[11.3.1.02,9.04,8]heptadec-13-en-1-yl] benzoate 在 氟化氢吡啶 作用下， 以 吡啶 为溶剂， 反应 3.0h， 以50%的产率得到[(1S,2S,4R,8S,9R,10S,11S,15S)-11-acetyloxy-8-(acetyloxymethyl)-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-10,14,17,17-tetramethyl-6,12-dioxo-3,7-dioxatetracyclo[11.3.1.02,9.04,8]heptadec-13-en-1-yl] 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：

  20-acetyl-2'-O-(tert-butyldimethylsilyl)-4-deacetyl-5,6-dehydro-7-oxo-5-O-secopaclitaxel 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以80%的产率得到[(1S,2S,4R,8S,9R,10S,11S,15S)-11-acetyloxy-8-(acetyloxymethyl)-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-10,14,17,17-tetramethyl-6,12-dioxo-3,7-dioxatetracyclo[11.3.1.02,9.04,8]heptadec-13-en-1-yl] 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