(R)-1-(2-(((Benzyloxy)carbonyl)amino)acetyl)pyrrolidine-2-carboxylic acid

• 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: (R)-1-(2-(((Benzyloxy)carbonyl)amino)acetyl)pyrrolidine-2-carboxylic acid
• 英文别名: (2R)-1-[2-(phenylmethoxycarbonylamino)acetyl]pyrrolidine-2-carboxylic acid
• 化学式: C₁₅H₁₈N₂O₅
• 分子量: 306.318
• InChiKey: ZTUKZKYDJMGJDC-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-1-((2R,4R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3,3-difluorotetrahydrofuran-2-yl)pyrimidin-2(1H)-one 、 (R)-1-(2-(((Benzyloxy)carbonyl)amino)acetyl)pyrrolidine-2-carboxylic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以83.4%的产率得到
  参考文献：
  名称：

  Enhanced anti-tumor efficiency of gemcitabine prodrug by FAPα-mediated activation

  摘要：

  Gemcitabine (Gem) as an anti-cancer agent has been limited by its short circulation time and rapid metabolism that reflects in low tumor uptake and low therapeutic efficiency. To improve its anti-tumor activity, a novel FAP alpha enzyme-activated prodrug of Z-GP-Gem modified at 4-amino group of Gem was developed, which could effectively release parent Gem based on the specific cleavage via FAP alpha enzyme-activation in tumor micro-environment. Compared to Gem, the Z-GP-Gem prodrug exhibited significantly enhanced inhibition of both tumor growth and pulmonary metastasis in BALB/c mice bearing orthotopic breast 4T1 tumors. The Z-GP-Gem prodrug has a prolonged circulation time and a high tumor uptake based on the modification of Z-GP dipeptide at 4-amino group of Gem. These eventually caused a marked improvement in the systemic toxicity and the tumor growth inhibition in 4T1 cells. More interestingly, the unexpected depletion of tumor-associated fibroblast (TAF) was observed during the treatment of Z-GP-Gem prodrug in animal model. Therefore, these findings demonstrated that the FAP alpha-activated prodrug Z-GP-Gem would be a desirable approach for tumor therapy by intravenous administration.

  DOI：

  10.1016/j.ijpharm.2019.01.032
• 作为产物：
  描述：

  N-苄氧羰基甘氨酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 2.33h， 生成 (R)-1-(2-(((Benzyloxy)carbonyl)amino)acetyl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  一个新的苯并三唑介导的2,5,5-二酮哌嗪杂成的立体挠性通道。

  摘要：

  开链CBZ-大号-AA 1 -大号-Pro-Bt基因（Bt基因=苯并三唑）序列转化成任一相应的反式-或顺式-融合根据反应条件2,5-二酮哌嗪（DKPs）。热力学串联环化/表位选择性地提供了相应的反式-DKP（69-75％）。互补地，串联脱保护/环化导致顺式-DKP（65-72％）。已制备了一组代表性的脯氨酸含顺式和反式DKP。基于手性HPLC，动力学和计算研究的机械研究使结果合理化。

  DOI：

  10.1002/chem.201103143