baccatin III 13-(N-benzoyl-isoserinate) | 131896-67-8

• 英文名称: baccatin III 13-(N-benzoyl-isoserinate)
• 英文别名: Baccatin III 13-(9S-N-benzoyl-iso-serinate)；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-(3-benzamido-2-hydroxypropanoyl)oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 131896-67-8
• 化学式: C₄₁H₄₇NO₁₄
• 分子量: 777.822
• InChiKey: XGCFAVZHJRXPHO-KGDHFGMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.99
• 重原子数：
  56.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  221.29
• 氢给体数：
  4.0
• 氢受体数：
  14.0

反应信息

• 作为产物：
  描述：

  7-O-(2,2,2-三氯乙氧基羰基)浆果赤霉素 III 在 4-二甲氨基吡啶 、 碳酸二(2-吡啶)酯 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 11.0h， 生成 baccatin III 13-(N-benzoyl-isoserinate)
  参考文献：
  名称：

  Biologically active taxol analogs with deleted A-ring side chain substituents and variable C-2' configurations

  摘要：

  Taxol (1), a potent inhibitor of cell replication, enhances the assembly of tubulin into stable microtubules and promotes the formation of microtubule bundles in cells. In addition to its unique mechanism of action, taxol exhibits unusual promise as an antitumor agent, but its application in cancer chemotherapy is hampered by its limited availability. In order to better define the structure-activity profile of taxol for the design of more accessible drugs and to provide insight into the chemical features of the taxol-microtubule interaction, taxol analogues 3-8, with deleted A-ring side chain substituents and both R and S C-2' configurations, were synthesized from baccatin III (2) through esterification at the hindered 13-hydroxyl. Employing an improved hydroxyl protection strategy, lactate analogues 3 and 4 were prepared with reasonable efficiency owing to their simple side-chain structures, while N-benzoylisoserine analogues 7 and 8 were synthesized through esterification reactions whose rates were enhanced greatly by the participation of the amide functionality. Although less biologically active than taxol, analogues 5-7 were found to promote the polymerization of tubulin and to be cytotoxic; 5 and 6 were considerably more effective than 7, whereas 3, 4, and 8 were least active. Interestingly, tubulin polymerization was sensitive to the C-2' configuration only when the amide substituent was present in the side chain. This observation suggests that the 3'-amide substituent plays an important role in preorganizing the taxol side chain to bind to microtubules.

  DOI：

  10.1021/jm00107a042