(S)-2-Allyloxycarbonylamino-4-(2-{2-[2-(2-azido-ethoxy)-ethoxy]-ethoxy}-ethylcarbamoyl)-butyric acid allyl ester | 239081-46-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-Allyloxycarbonylamino-4-(2-{2-[2-(2-azido-ethoxy)-ethoxy]-ethoxy}-ethylcarbamoyl)-butyric acid allyl ester
• CAS: 239081-46-0
• 化学式: C₂₀H₃₃N₅O₈
• 分子量: 471.511
• InChiKey: HFJFKNXVVVULQJ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.25
• 重原子数：
  33.0
• 可旋转键数：
  21.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  170.18
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (S)-2-Allyloxycarbonylamino-4-(2-{2-[2-(2-azido-ethoxy)-ethoxy]-ethoxy}-ethylcarbamoyl)-butyric acid allyl ester 在 4-二甲氨基吡啶 、 水 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 60.0h， 生成 (S)-2-Allyloxycarbonylamino-4-{2-[2-(2-{2-[2-(carboxymethyl-methyl-amino)-acetylamino]-ethoxy}-ethoxy)-ethoxy]-ethylcarbamoyl}-butyric acid allyl ester
  参考文献：
  名称：

  Synthesis and Evaluation of Taxol–Folic Acid Conjugates as Targeted Antineoplastics † †See ref 1.

  摘要：

  A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid, One agent (54), further evaluated in animal Studies as found to increase the lifespan in mice, but was less effective than Taxol itself. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00019-6
• 作为产物：
  描述：

  1-氨基-11-叠氮-3,6,9-三氧杂十一烷 、 N-allyloxycarbonyl α-allyl-L-glutamate 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.0h， 以94%的产率得到(S)-2-Allyloxycarbonylamino-4-(2-{2-[2-(2-azido-ethoxy)-ethoxy]-ethoxy}-ethylcarbamoyl)-butyric acid allyl ester
  参考文献：
  名称：

  Synthesis and Evaluation of Taxol–Folic Acid Conjugates as Targeted Antineoplastics † †See ref 1.

  摘要：

  A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid, One agent (54), further evaluated in animal Studies as found to increase the lifespan in mice, but was less effective than Taxol itself. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00019-6

文献信息

• Reduction of Azides to Primary Amines in Substrates Bearing Labile Ester Functionality. Synthesis of a PEG-Solubilized, “Y”-Shaped Iminodiacetic Acid Reagent for Preparation of Folate-Tethered Drugs¹
  作者：Jae Wook Lee、Philip L. Fuchs

  DOI：10.1021/ol9905248

  日期：1999.7.1

  Anhydride 3 is a useful reagent for the synthesis of triply linked drug conjugates. Examples using paclitaxel are provided. Conversion of the azido moiety to a primary amine in the presence of substrates bearing labile ester functionality requires the use of a tin/mercaptan reducing system which includes methanol exchange equilibration to effect nitrogen-tin bond scission.