N-(N(α)-tert-butoxycarbonyl-O(γ)-tert-butyl-L-aspartyl)-5-aminolaevulinic acid methyl ester

• 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: N-(N(α)-tert-butoxycarbonyl-O(γ)-tert-butyl-L-aspartyl)-5-aminolaevulinic acid methyl ester
• 英文别名: methyl 5-[[(2S)-4-[(2-methylpropan-2-yl)oxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoyl]amino]-4-oxopentanoate
• 化学式: C₁₉H₃₂N₂O₈
• 分子量: 416.472
• InChiKey: ONCYHFPWZDYCBE-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(N(α)-tert-butoxycarbonyl-O(γ)-tert-butyl-L-aspartyl)-5-aminolaevulinic acid methyl ester 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.67h， 生成
  参考文献：
  名称：

  Improved Peptide Prodrugs of 5-ALA for PDT: Rationalization of Cellular Accumulation and Protoporphyrin IX Production by Direct Determination of Cellular Prodrug Uptake and Prodrug Metabolization

  摘要：

  Twenty-seven dipeptide derivatives of general structure Ac-Xaa-ALA-OR were synthesized as potential prodrugs for 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). Xaa is an (x-amino acid, chosen to provide a prodrug with appropriately tailored lipophilicity and water solubility. Although no simple correlation is observed between downstream production of protoporphyrin IX (PpIX) in PAM212 keratinocytes and HPLC-derived descriptors of compound lipophilicity, quantification of prodrug uptake reveals that most of the dipeptides are actually more efficiently accumulated than ALA in PAM212 and also A549 and Caco-2 cell lines. Subsequent ALA release is the limiting factor, which emphasizes the importance of decoupling prodrug uptake and intracellular metabolization when assessing the efficacy of ALA derivatives for PDT. In agreement with PpIX fluorescence studies, at,I concentration of 0.1 MM, L-Phe derivatives 4m and 4o, and L-Leu, L-Met, and L-Glu derivatives 4f, 4k, and 4u, exhibit significantly enhanced photoxicity in PAM212 cells compared to ALA.

  DOI：

  10.1021/jm900224r
• 作为产物：
  描述：

  BOC-L-天门冬氨酸4-叔丁基-1-羟基-琥珀酰亚胺酯 、 5-氨基酮戊酸甲酯盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以98%的产率得到N-(N(α)-tert-butoxycarbonyl-O(γ)-tert-butyl-L-aspartyl)-5-aminolaevulinic acid methyl ester
  参考文献：
  名称：

  Improved Peptide Prodrugs of 5-ALA for PDT: Rationalization of Cellular Accumulation and Protoporphyrin IX Production by Direct Determination of Cellular Prodrug Uptake and Prodrug Metabolization

  摘要：

  Twenty-seven dipeptide derivatives of general structure Ac-Xaa-ALA-OR were synthesized as potential prodrugs for 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). Xaa is an (x-amino acid, chosen to provide a prodrug with appropriately tailored lipophilicity and water solubility. Although no simple correlation is observed between downstream production of protoporphyrin IX (PpIX) in PAM212 keratinocytes and HPLC-derived descriptors of compound lipophilicity, quantification of prodrug uptake reveals that most of the dipeptides are actually more efficiently accumulated than ALA in PAM212 and also A549 and Caco-2 cell lines. Subsequent ALA release is the limiting factor, which emphasizes the importance of decoupling prodrug uptake and intracellular metabolization when assessing the efficacy of ALA derivatives for PDT. In agreement with PpIX fluorescence studies, at,I concentration of 0.1 MM, L-Phe derivatives 4m and 4o, and L-Leu, L-Met, and L-Glu derivatives 4f, 4k, and 4u, exhibit significantly enhanced photoxicity in PAM212 cells compared to ALA.

  DOI：

  10.1021/jm900224r

文献信息

• Ethylene Glycol and Amino Acid Derivatives of 5-Aminolevulinic Acid as New Photosensitizing Precursors of Protoporphyrin IX in Cells
  作者：Yann Berger、Alain Greppi、Olivier Siri、Reinhard Neier、Lucienne Juillerat-Jeanneret

  DOI：10.1021/jm000981q

  日期：2000.12.1

  of cancer and is synthesized intracellularly from aminolevulinic acid (ALA) precursors. To evaluate means to specifically target ALA derivatives to defined cells, we have synthesized and characterized ethylene glycol esters and amino acid pseudodipeptide derivatives of ALA as potential specific substrates for cellular esterases and aminopeptidases, respectively. The PpIX formation induced by these

  原卟啉IX（PpIX）在癌症的光动力检测和治疗（PDT）中用作光敏剂，由氨基乙酰丙酸（ALA）前体在细胞内合成。为了评估将ALA衍生物特异性靶向特定细胞的方法，我们合成并表征了ALA的乙二醇酯和氨基酸假二肽衍生物分别作为细胞酯酶和氨基肽酶的潜在特异性底物。使用人类和大鼠的癌细胞系和内皮细胞培养物研究了由这些产物诱导的PpIX形成。这些化合物在没有光照的情况下的细胞毒性也得到了控制。结果表明，乙二醇酯可以诱导高水平的PpIX，并在低于其细胞毒性阈值的浓度下有用。
• Improved Peptide Prodrugs of 5-ALA for PDT: Rationalization of Cellular Accumulation and Protoporphyrin IX Production by Direct Determination of Cellular Prodrug Uptake and Prodrug Metabolization
  作者：Francesca Giuntini、Ludovic Bourré、Alexander J. MacRobert、Michael Wilson、Ian M. Eggleston

  DOI：10.1021/jm900224r

  日期：2009.7.9

  Twenty-seven dipeptide derivatives of general structure Ac-Xaa-ALA-OR were synthesized as potential prodrugs for 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). Xaa is an (x-amino acid, chosen to provide a prodrug with appropriately tailored lipophilicity and water solubility. Although no simple correlation is observed between downstream production of protoporphyrin IX (PpIX) in PAM212 keratinocytes and HPLC-derived descriptors of compound lipophilicity, quantification of prodrug uptake reveals that most of the dipeptides are actually more efficiently accumulated than ALA in PAM212 and also A549 and Caco-2 cell lines. Subsequent ALA release is the limiting factor, which emphasizes the importance of decoupling prodrug uptake and intracellular metabolization when assessing the efficacy of ALA derivatives for PDT. In agreement with PpIX fluorescence studies, at,I concentration of 0.1 MM, L-Phe derivatives 4m and 4o, and L-Leu, L-Met, and L-Glu derivatives 4f, 4k, and 4u, exhibit significantly enhanced photoxicity in PAM212 cells compared to ALA.