1-O-(tert-butyldimethylsilyl)-3-[2-(N-Z-L-valyloxy)-4,6-dimethylphenyl]-3,3-dimethylpropan-1-ol | 380306-31-0

• 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: 1-O-(tert-butyldimethylsilyl)-3-[2-(N-Z-L-valyloxy)-4,6-dimethylphenyl]-3,3-dimethylpropan-1-ol
• CAS: 380306-31-0
• 化学式: C₃₂H₄₉NO₅Si
• 分子量: 555.83
• InChiKey: DVMJLKUEXJVZCD-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.85
• 重原子数：
  39.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  73.86
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-O-(tert-butyldimethylsilyl)-3-[2-(N-Z-L-valyloxy)-4,6-dimethylphenyl]-3,3-dimethylpropan-1-ol 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 1-O-(tert-butyldimethylsilyl)-3-[2-(N-Boc-L-prolyl-L-valyloxy)-4,6-dimethylphenyl]-3,3-dimethylpropan-1-ol
  参考文献：
  名称：

  Coumarin Derivatives as Protease-Sensitive Prodrugs

  摘要：

  To overcome the lack of selectivity of anticancer drugs toward malignant cells, the development of prodrugs, which could be activated selectively by tumour-specific proteases is the goal of these studies. In this work tripartate prodrugs have been evaluated consisting of a carrier unit and a spacer group, which allows for intramolecular cyclisation while releasing the third component, the compound attached to the carboxylic acid moiety of the spacer group. As carrier units amino acids or peptides have been used, which are required for recognition by the protease. As the spacer unit the "trimethyl-lock"-spacer has been applied; as a model leaving group p-anisidine was attached to the carboxylic acid moiety. It was intended to test the compounds for their releasing rate of p-anisidine. Two of the evaluated compounds, 9b and 9h, were degraded with half-lives of 46 min at room temperature. However, the poor solubility in aqueous solutions proved the major disadvantage of the TML-based prodrugs.

  DOI：

  10.1002/1521-4184(200106)334:6<209::aid-ardp209>3.0.co;2-y
• 作为产物：
  描述：

  CBZ-L-缬氨酸 、 2-(4-((叔丁基二甲基硅烷基)氧基)-2-甲基丁-2-基)-3,5-二甲基苯酚 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以65%的产率得到1-O-(tert-butyldimethylsilyl)-3-[2-(N-Z-L-valyloxy)-4,6-dimethylphenyl]-3,3-dimethylpropan-1-ol
  参考文献：
  名称：

  Coumarin Derivatives as Protease-Sensitive Prodrugs

  摘要：

  To overcome the lack of selectivity of anticancer drugs toward malignant cells, the development of prodrugs, which could be activated selectively by tumour-specific proteases is the goal of these studies. In this work tripartate prodrugs have been evaluated consisting of a carrier unit and a spacer group, which allows for intramolecular cyclisation while releasing the third component, the compound attached to the carboxylic acid moiety of the spacer group. As carrier units amino acids or peptides have been used, which are required for recognition by the protease. As the spacer unit the "trimethyl-lock"-spacer has been applied; as a model leaving group p-anisidine was attached to the carboxylic acid moiety. It was intended to test the compounds for their releasing rate of p-anisidine. Two of the evaluated compounds, 9b and 9h, were degraded with half-lives of 46 min at room temperature. However, the poor solubility in aqueous solutions proved the major disadvantage of the TML-based prodrugs.

  DOI：

  10.1002/1521-4184(200106)334:6<209::aid-ardp209>3.0.co;2-y