13-(3'-N-benzyloxycarbonylphenylisoserine)-10-deacetyl-7,10-dibenzyloxycarbonylbaccatin III | 850933-54-9

• 英文名称: 13-(3'-N-benzyloxycarbonylphenylisoserine)-10-deacetyl-7,10-dibenzyloxycarbonylbaccatin III
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1-hydroxy-15-[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylmethoxycarbonylamino)propanoyl]oxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis(phenylmethoxycarbonyloxy)-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 850933-54-9
• 化学式: C₆₂H₆₃NO₁₈
• 分子量: 1110.18
• InChiKey: MKFNDEYPOHYVFT-SRXKZZDYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  81
• 可旋转键数：
  24
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  255
• 氢给体数：
  3
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  13-(3'-N-benzyloxycarbonylphenylisoserine)-10-deacetyl-7,10-dibenzyloxycarbonylbaccatin III 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 8.0h， 生成 10-去乙酰基-N-去苯甲酰基紫杉醇
  参考文献：
  名称：

  No Auxiliary, No Byproduct Strategy for Water-Soluble Prodrugs of Taxoids:  Scope and Limitation of O−N Intramolecular Acyl and Acyloxy Migration Reactions

  摘要：

  Since numerous new taxoids active against multidrug resistant (MDR) tumors have been developed and their poor water-solubility is a very real problem in intravenous administration, we have designed and synthesized a series of novel water-soluble taxoid prodrugs (isotaxoids). These prodrugs, a 2'-O-isoform of taxoids, showed promising results with higher water solubility (0.8- 1.1 mg/mL) and proper kinetics for parent drug release by a simple pH-dependent chemical mechanism via O-N intramolecular acyl migration. No additional functional auxiliaries are released during the conversion to parent drugs, which would be an advantage in toxicology and general pharmacology, and the cost for the evaluations of auxiliary units in these fields could be saved in prodrug development. In addition, we demonstrate for the first time the successful application of the O-N intramolecular acyloxy migration reaction in the prodrug design, with the exception of the tert-butyloxycarbonyl group, and that this reaction can be provided with no organic solvent and no side products.

  DOI：

  10.1021/jm049344g
• 作为产物：
  描述：

  (2R,3S)-3-苯基异丝氨酸盐酸盐 在 4-二甲氨基吡啶 、 氢氧化钾 、 氯化亚砜 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 12.0h， 生成 13-(3'-N-benzyloxycarbonylphenylisoserine)-10-deacetyl-7,10-dibenzyloxycarbonylbaccatin III
  参考文献：
  名称：

  No Auxiliary, No Byproduct Strategy for Water-Soluble Prodrugs of Taxoids:  Scope and Limitation of O−N Intramolecular Acyl and Acyloxy Migration Reactions

  摘要：

  Since numerous new taxoids active against multidrug resistant (MDR) tumors have been developed and their poor water-solubility is a very real problem in intravenous administration, we have designed and synthesized a series of novel water-soluble taxoid prodrugs (isotaxoids). These prodrugs, a 2'-O-isoform of taxoids, showed promising results with higher water solubility (0.8- 1.1 mg/mL) and proper kinetics for parent drug release by a simple pH-dependent chemical mechanism via O-N intramolecular acyl migration. No additional functional auxiliaries are released during the conversion to parent drugs, which would be an advantage in toxicology and general pharmacology, and the cost for the evaluations of auxiliary units in these fields could be saved in prodrug development. In addition, we demonstrate for the first time the successful application of the O-N intramolecular acyloxy migration reaction in the prodrug design, with the exception of the tert-butyloxycarbonyl group, and that this reaction can be provided with no organic solvent and no side products.

  DOI：

  10.1021/jm049344g