Isobutyric acid (1R,2S)-2-tert-butoxycarbonylamino-1-carboxy-2-phenyl-ethyl ester | 655228-34-5

• 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: Isobutyric acid (1R,2S)-2-tert-butoxycarbonylamino-1-carboxy-2-phenyl-ethyl ester
• CAS: 655228-34-5
• 化学式: C₁₈H₂₅NO₆
• 分子量: 351.4
• InChiKey: RCCQPPHLFBHHQQ-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101.93
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Isobutyric acid (1R,2S)-2-tert-butoxycarbonylamino-1-carboxy-2-phenyl-ethyl ester 在 盐酸 、 4-二甲氨基吡啶 、 phosphate buffered saline 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 苯甲醚 为溶剂， 生成 (2R,3S)-2-Hydroxy-3-isobutyrylamino-3-phenyl-propionic acid cyclohexyl ester
  参考文献：
  名称：

  O–N Intramolecular acyl migration strategy in water-soluble prodrugs of taxoids

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2003.09.020
• 作为产物：
  描述：

  (2R,3S)-3-苯基异丝氨酸盐酸盐 在 吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 Isobutyric acid (1R,2S)-2-tert-butoxycarbonylamino-1-carboxy-2-phenyl-ethyl ester
  参考文献：
  名称：

  O–N Intramolecular acyl migration strategy in water-soluble prodrugs of taxoids

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2003.09.020