2'-t-BOC-L-phenylalanyltaxol | 117527-54-5

• 英文名称: 2'-t-BOC-L-phenylalanyltaxol
• CAS: 117527-54-5
• 化学式: C₆₁H₆₈N₂O₁₇
• 分子量: 1101.21
• InChiKey: RUBDHZUZMYLFRJ-QMOYVKEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.42
• 重原子数：
  80.0
• 可旋转键数：
  15.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  265.69
• 氢给体数：
  4.0
• 氢受体数：
  17.0

反应信息

• 作为产物：
  描述：

  BOC-L-苯丙氨酸 、 紫杉醇 在 吡啶 、 对甲苯磺酰氯 作用下， 生成 2'-t-BOC-L-phenylalanyltaxol
  参考文献：
  名称：

  Synthesis of congeners and prodrugs. 3. Water-soluble prodrugs of taxol with potent antitumor activity

  摘要：

  Taxol has shown good in vivo antitumor activity in a number of test systems. The formulation of taxol for antitumor testing has been difficult. Esterification at either C-2' or C-7 resulted in loss of in vitro tubulin assembly activity but not cytotoxicity. These observations suggested that esters at C-2' and/or C-7, which would tend to promote water solubility, might serve as useful prodrugs of taxol. The reaction of taxol with either succinic anhydride or glutaric anhydride in pyridine solution at room temperature gave the crystalline mono 2'-adducts 1b and 1f, respectively. Salts of these acids (1b, 1f, 1i) were formed by the addition of 1 equiv of the corresponding base, followed by evaporation and/or freeze-drying of the solvent(s). The salts had improved antitumor activity as compared to the free acids. The triethanolamine and N-methylglucamine salts showed greatly improved aqueous solubility and were more active than the sodium salts. The glutarate series was preferred because of the higher activity and the higher yields obtained. 2'-Glutaryltaxol (1f) was coupled with 3-(dimethylamino)-1-propylamine, using CDI, to form in excellent yield the amino amide 1o. The hydrochloride salt (1p) showed good solubility and was extremely potent and active. At 10 mg/kg, in the B16 screen, 1p gave a T/C of 352 with 5 out of 10 cures. In the MX-1 breast xenograft assay, this prodrug gave values of -100 at doses of 40 and 20 mg/kg, with all live animals being tumor free.

  DOI：

  10.1021/jm00124a011