4-O-benzyl 1-O-methyl (2S)-2-[[3-[2-bis(phenylmethoxy)phosphoryloxy-4,6-dimethylphenyl]-3-methylbutanoyl]amino]butanedioate | 183867-89-2

• 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: 4-O-benzyl 1-O-methyl (2S)-2-[[3-[2-bis(phenylmethoxy)phosphoryloxy-4,6-dimethylphenyl]-3-methylbutanoyl]amino]butanedioate
• CAS: 183867-89-2
• 化学式: C₃₉H₄₄NO₉P
• 分子量: 701.753
• InChiKey: DCRMLLBIGALCJW-XIFFEERXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  50
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-O-benzyl 1-O-methyl (2S)-2-[[3-[2-bis(phenylmethoxy)phosphoryloxy-4,6-dimethylphenyl]-3-methylbutanoyl]amino]butanedioate 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以61%的产率得到(3S)-3-[[3-(2,4-dimethyl-6-phosphonooxyphenyl)-3-methylbutanoyl]amino]-4-methoxy-4-oxobutanoic acid
  参考文献：
  名称：

  Phosphate Prodrugs for Amines Utilizing a Fast Intramolecular Hydroxy Amide Lactonization

  摘要：

  A novel phosphate prodrug system for amines, amino acids, peptides, and peptide mimetics, which utilizes a fast hydroxy amide lactonization of a 3-(2'-hydroxy-4',6'-dimethylphenyl) -3,3-dimethylpropionic amide system, was developed. Prodrugs of five model amine/amino acids, including p-anisidine, GlyOMe, PheOMe, LysOMe, and Asp-alpha-OMe, were synthesized. The syntheses of these model phosphate prodrugs were accomplished by coupling the amine or the protected amino acids with 3-[2'-(dibenzylphosphono)oxy-4',6'-dimethylphenyl]-3,3-dimethylpropionic acid using coupling agents such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride and 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride, followed by hydrogenolysis. These phosphate prodrugs were evaluated as substrates for the human placental alkaline phosphatase (AP). The structural features of the amine/amino acids attached to the carboxylic acid group of the promoiety were not found to significantly affect the substrate activity for AP, as evidenced by the small variations observed in the Michaelis-Menten parameters (K-m and V-max) of the phosphate prodrugs. Results obtained from this study suggest that such a phosphate prodrug system may be applied to a variety of structurally diverse amine-containing drugs.

  DOI：

  10.1021/jo961477p
• 作为产物：
  描述：

  Boc-L-天冬氨酸 4-苄酯 在 TEA 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成 4-O-benzyl 1-O-methyl (2S)-2-[[3-[2-bis(phenylmethoxy)phosphoryloxy-4,6-dimethylphenyl]-3-methylbutanoyl]amino]butanedioate
  参考文献：
  名称：

  Phosphate Prodrugs for Amines Utilizing a Fast Intramolecular Hydroxy Amide Lactonization

  摘要：

  A novel phosphate prodrug system for amines, amino acids, peptides, and peptide mimetics, which utilizes a fast hydroxy amide lactonization of a 3-(2'-hydroxy-4',6'-dimethylphenyl) -3,3-dimethylpropionic amide system, was developed. Prodrugs of five model amine/amino acids, including p-anisidine, GlyOMe, PheOMe, LysOMe, and Asp-alpha-OMe, were synthesized. The syntheses of these model phosphate prodrugs were accomplished by coupling the amine or the protected amino acids with 3-[2'-(dibenzylphosphono)oxy-4',6'-dimethylphenyl]-3,3-dimethylpropionic acid using coupling agents such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride and 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride, followed by hydrogenolysis. These phosphate prodrugs were evaluated as substrates for the human placental alkaline phosphatase (AP). The structural features of the amine/amino acids attached to the carboxylic acid group of the promoiety were not found to significantly affect the substrate activity for AP, as evidenced by the small variations observed in the Michaelis-Menten parameters (K-m and V-max) of the phosphate prodrugs. Results obtained from this study suggest that such a phosphate prodrug system may be applied to a variety of structurally diverse amine-containing drugs.

  DOI：

  10.1021/jo961477p

文献信息

• Phosphate Prodrugs for Amines Utilizing a Fast Intramolecular Hydroxy Amide Lactonization
  作者：Michalis G. Nicolaou、Chong-Sheng Yuan、Ronald T. Borchardt

  DOI：10.1021/jo961477p

  日期：1996.1.1

  A novel phosphate prodrug system for amines, amino acids, peptides, and peptide mimetics, which utilizes a fast hydroxy amide lactonization of a 3-(2'-hydroxy-4',6'-dimethylphenyl) -3,3-dimethylpropionic amide system, was developed. Prodrugs of five model amine/amino acids, including p-anisidine, GlyOMe, PheOMe, LysOMe, and Asp-alpha-OMe, were synthesized. The syntheses of these model phosphate prodrugs were accomplished by coupling the amine or the protected amino acids with 3-[2'-(dibenzylphosphono)oxy-4',6'-dimethylphenyl]-3,3-dimethylpropionic acid using coupling agents such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride and 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride, followed by hydrogenolysis. These phosphate prodrugs were evaluated as substrates for the human placental alkaline phosphatase (AP). The structural features of the amine/amino acids attached to the carboxylic acid group of the promoiety were not found to significantly affect the substrate activity for AP, as evidenced by the small variations observed in the Michaelis-Menten parameters (K-m and V-max) of the phosphate prodrugs. Results obtained from this study suggest that such a phosphate prodrug system may be applied to a variety of structurally diverse amine-containing drugs.