N-(N-acetyl-D-leucyl)-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-acetyl-D-leucyl)-5-aminolaevulinic acid methyl ester
• 英文别名: methyl 5-[[(2R)-2-acetamido-4-methylpentanoyl]amino]-4-oxopentanoate
• 化学式: C₁₄H₂₄N₂O₅
• 分子量: 300.355
• InChiKey: CFIYXBZHTGQXOS-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氨基乙酰丙酸盐酸盐 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 为溶剂， 反应 2.67h， 生成 N-(N-acetyl-D-leucyl)-5-aminolaevulinic acid methyl ester
  参考文献：
  名称：

  有效合成5-氨基戊酸（ALA）的肽，用于光动力疗法

  摘要：

  已经设计了一种有效且具有成本效益的方法来制备氨基甲酸酯保护的5-氨基戊二酸（5-ALA）二肽酯衍生物，该方法避免了在碱性条件下与5-ALA的不稳定性相关的问题。该方法还适用于以高对映体纯度直接合成N-（α）-乙酰基氨基酸-ALA二肽，作为光动力疗法（PDT）的潜在新药。

  DOI：

  10.1016/j.tet.2005.05.036

文献信息

• 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.
• An efficient synthesis of 5-aminolaevulinic acid (ALA)-containing peptides for use in photodynamic therapy
  作者：Louis M.-A. Rogers、Philip G. McGivern、Anthony R. Butler、Alexander J. MacRobert、Ian M. Eggleston

  DOI：10.1016/j.tet.2005.05.036

  日期：2005.7

  cost-effective procedure has been devised for the preparation of urethane-protected 5-aminolaevulinic acid (5-ALA) dipeptide ester derivatives which avoids problems associated with the instability of 5-ALA under basic conditions. The procedure is also applicable to the direct synthesis of N-(α)-acetyl amino acid-ALA dipeptides in high enantiomeric purity as potential novel prodrugs for photodynamic therapy

  已经设计了一种有效且具有成本效益的方法来制备氨基甲酸酯保护的5-氨基戊二酸（5-ALA）二肽酯衍生物，该方法避免了在碱性条件下与5-ALA的不稳定性相关的问题。该方法还适用于以高对映体纯度直接合成N-（α）-乙酰基氨基酸-ALA二肽，作为光动力疗法（PDT）的潜在新药。