(2aR,4S,4aS,6R,9R,10R,10aR,10bS,E)-10b-acetoxy-7-(1-(1,3-dioxoisoindolin-2-yl)propan-2-ylidene)-9-hydroxy-4a,8,8-trimethyl-5-oxo-4-((triethylsilyl)oxy)dodecahydro-1H-6,9-epoxycycloocta[3,4]benzo[1,2-b]oxet-10-yl benzoate | 202996-22-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2aR,4S,4aS,6R,9R,10R,10aR,10bS,E)-10b-acetoxy-7-(1-(1,3-dioxoisoindolin-2-yl)propan-2-ylidene)-9-hydroxy-4a,8,8-trimethyl-5-oxo-4-((triethylsilyl)oxy)dodecahydro-1H-6,9-epoxycycloocta[3,4]benzo[1,2-b]oxet-10-yl benzoate
• CAS: 202996-22-3
• 化学式: C₄₂H₅₁NO₁₁Si
• 分子量: 773.953
• InChiKey: UXIWMTTZRMMTRD-JCRDBTMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.64
• 重原子数：
  55.0
• 可旋转键数：
  10.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  154.97
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (2aR,4S,4aS,6R,9R,10R,10aR,10bS,E)-10b-acetoxy-7-(1-(1,3-dioxoisoindolin-2-yl)propan-2-ylidene)-9-hydroxy-4a,8,8-trimethyl-5-oxo-4-((triethylsilyl)oxy)dodecahydro-1H-6,9-epoxycycloocta[3,4]benzo[1,2-b]oxet-10-yl benzoate 在 甲胺 作用下， 以 乙醇 为溶剂， 反应 22.0h， 以88.7%的产率得到7-(triethylsilyl)-13-amino-14-nor-seco-10-deacetylbaccatin III
  参考文献：
  名称：

  Syntheses and Structure−Activity Relationships of Novel Nor-seco Taxoids

  摘要：

  A series of novel nor-seco taxoids (4a-b, 5a-d, 6), including either a C-13 ester linkage or a C-13 amide linkage, was synthesized by means of the p-lactam synthon method using the coupling of (3R,4S)-1-acyl-beta-lactams with properly protected nor-seco baccatin III derivatives (1, 2, 3) as the key step. Nor-seco baccatin III derivatives were prepared through oxidative cleavage of the A ring of 14 beta-hydroxy-10-deacetylbaccatin III followed by reduction, amination using Mitsunobu conditions, or reductive amination. Nor-seco taxoids with a C-13 ester linkage (4a-b) or a C-13 N-Me amide linkage (6) show reduced cytotoxicity against human cancer cell lines as compared with paclitaxel, but still retain a certain level of activity despite the destruction of the taxane A ring. However, none of the analogues with a C-13 N-H amide linkage (5a-d) exhibit appreciable activity (IC50 > 1.0 mu M). A restrained molecular dynamics study reveals the inability of 5a-d to attain the proposed bioactive conformation, which accounts for the loss of activity.

  DOI：

  10.1021/jo971953r
• 作为产物：
  描述：

  13-formyl-14-nor-seco-10-deacetylbaccatin III 在 4-二甲氨基吡啶 、 TEA 、 sodium cyanoborohydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 40.33h， 生成 (2aR,4S,4aS,6R,9R,10R,10aR,10bS,E)-10b-acetoxy-7-(1-(1,3-dioxoisoindolin-2-yl)propan-2-ylidene)-9-hydroxy-4a,8,8-trimethyl-5-oxo-4-((triethylsilyl)oxy)dodecahydro-1H-6,9-epoxycycloocta[3,4]benzo[1,2-b]oxet-10-yl benzoate
  参考文献：
  名称：

  Syntheses and Structure−Activity Relationships of Novel Nor-seco Taxoids

  摘要：

  A series of novel nor-seco taxoids (4a-b, 5a-d, 6), including either a C-13 ester linkage or a C-13 amide linkage, was synthesized by means of the p-lactam synthon method using the coupling of (3R,4S)-1-acyl-beta-lactams with properly protected nor-seco baccatin III derivatives (1, 2, 3) as the key step. Nor-seco baccatin III derivatives were prepared through oxidative cleavage of the A ring of 14 beta-hydroxy-10-deacetylbaccatin III followed by reduction, amination using Mitsunobu conditions, or reductive amination. Nor-seco taxoids with a C-13 ester linkage (4a-b) or a C-13 N-Me amide linkage (6) show reduced cytotoxicity against human cancer cell lines as compared with paclitaxel, but still retain a certain level of activity despite the destruction of the taxane A ring. However, none of the analogues with a C-13 N-H amide linkage (5a-d) exhibit appreciable activity (IC50 > 1.0 mu M). A restrained molecular dynamics study reveals the inability of 5a-d to attain the proposed bioactive conformation, which accounts for the loss of activity.

  DOI：

  10.1021/jo971953r