3'-N-debenzoyl-3'-N-Troc-7-Troc-paclitaxel | 602319-12-0

• 英文名称: 3'-N-debenzoyl-3'-N-Troc-7-Troc-paclitaxel
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-1-hydroxy-15-[(2R,3S)-2-hydroxy-3-phenyl-3-(2,2,2-trichloroethoxycarbonylamino)propanoyl]oxy-10,14,17,17-tetramethyl-11-oxo-9-(2,2,2-trichloroethoxycarbonyloxy)-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 602319-12-0
• 化学式: C₄₆H₄₉Cl₆NO₁₇
• 分子量: 1100.61
• InChiKey: LDNZDZLTDNKMIJ-BGKJQISDSA-N

物化性质

• 熔点：
  150-152 °C
• 沸点：
  1013.8±65.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  70
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  246
• 氢给体数：
  3
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  3'-N-debenzoyl-3'-N-Troc-7-Troc-paclitaxel 在 碳酸氢钠 、 溶剂黄146 、 锌 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 10.0h， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-1,9-dihydroxy-15-[(2R,3S)-2-hydroxy-3-phenyl-3-(propan-2-yloxycarbonylamino)propanoyl]oxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  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：

  在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 以13 g的产率得到3'-N-debenzoyl-3'-N-Troc-7-Troc-paclitaxel
  参考文献：
  名称：

  WO2023/77129

  摘要：

  公开号：

文献信息

• A Novel Approach of Water-Soluble Paclitaxel Prodrug with No Auxiliary and No Byproduct:  Design and Synthesis of Isotaxel
  作者：Yoshio Hayashi、Mariusz Skwarczynski、Yoshio Hamada、Youhei Sohma、Tooru Kimura、Yoshiaki Kiso

  DOI：10.1021/jm034112n

  日期：2003.8.1

  A novel water-soluble paclitaxel prodrug, isotaxel 2, that realizes a higher water-solubility and the formation of paclitaxel through a simple pH-dependent chemical mechanism via the O-N acyl migration was synthesized and showed promising results in water-solubility and kinetics. This prodrug, a 2'-O-benzoyl isoform of paclitaxel, has no additional functional auxiliaries released during conversion to paclitaxel, which would be a great advantage in toxicology and medical economics.
• O–N Intramolecular acyl migration strategy in water-soluble prodrugs of taxoids
  作者：Mariusz Skwarczynski、Youhei Sohma、Maiko Kimura、Yoshio Hayashi、Tooru Kimura、Yoshiaki Kiso

  DOI：10.1016/j.bmcl.2003.09.020

  日期：2003.12

  We synthesized a highly water-soluble canadensol prodrug 6 that formed canadensol 3 by a simple pH-dependent chemical mechanism via the O-N intramolecular acyl migration of the isobutyryl group. This prodrug, a 2'-O-isobutyryl isoform of 3, has no additional functional auxiliaries released during the conversion to 3. This is a significant advantage in toxicology and medical economics, since the potential side effects of reported water-soluble auxiliaries and the use of detergent for solubilization can be avoided. The solubility of 6 was 2.26 mg mL(-1) and only the parent drug 3 was released under physiological conditions (pH = 7.4) while, in acidic medium, the release of 3 slowed until migration was completely obstructed at pH = 2. In further consideration of this strategy, we elucidated the use of an 'O-N acyl-like' migration reaction of the Boc group in the design of a docetaxel prodrug. Both O-N migration and undesired hydrolysis of the Boc group occurred under physiological conditions, although no oxazolidinone formation was observed, suggesting the limitation of our water-soluble prodrug strategy to docetaxel. (C) 2003 Elsevier Ltd. All rights reserved.