(S)-4-(tert-Butoxycarbonyl-methyl-amino)-5-hydroxy-pentanoic acid tert-butyl ester | 156143-41-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-4-(tert-Butoxycarbonyl-methyl-amino)-5-hydroxy-pentanoic acid tert-butyl ester
• 英文别名: tert-butyl (4S)-5-hydroxy-4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pentanoate
• CAS: 156143-41-8
• 化学式: C₁₅H₂₉NO₅
• 分子量: 303.399
• InChiKey: VXXKOPYLFUJOAX-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-4-(tert-Butoxycarbonyl-methyl-amino)-5-hydroxy-pentanoic acid tert-butyl ester 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 碘 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 (S)-5-[(S)-4-tert-Butoxycarbonyl-2-(tert-butoxycarbonyl-methyl-amino)-butyldisulfanyl]-4-(tert-butoxycarbonyl-methyl-amino)-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  Investigation of the Active Site of Aminopeptidase A Using a Series of New Thiol-Containing Inhibitors

  摘要：

  Aminopeptidase A (APA) and aminopeptidase N (APN) are two metallopeptidases which have been suggested to be involved in the enzymatic cascade of the renin-angiotensin system. APA liberates angotensin III from angiotensin II by releasing the N-terminal aspartate, and APN participates in the inactivation of angiotensin III. As the role of angiotensin III in the regulation of blood pressure in the central nervous system and at the periphery is controversial, it was of interest to develop selective and efficient inhibitors of APA. Starting from Glu-thiol,(1) which was the first efficient APA inhibitor described, but however is equipotent on APA (K-i = 0.14 mu M) and APN (K-i = 0.12 mu M), beta-amino thiols bearing various carboxyalkyl chains have been synthesized and their inhibitory potencies measured on both purified enzymes. Compounds containing a carboxylated aromatic ring inhibited APA and APN with K-i values in the micromolar range but were slightly more active on APA. Conversely, inhibitors containing a cyclohexyl ring were more efficient on APN. Various modifications of the structure of Glu-thiol decreased inhibitory activity on both enzymes but increased the selectivity for APA, and compound 9d ((S)-4-amino-6-mercaptohexanoic acid) was 23 times more potent on APA (K-i = 2.0 mu M) than on APN (K-i = 45 mu M).

  DOI：

  10.1021/jm00035a014
• 作为产物：
  描述：

  (S)-2-(tert-Butoxycarbonyl-methyl-amino)-pentanedioic acid 5-tert-butyl ester 1-methyl ester 在 sodium tetrahydroborate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以88%的产率得到(S)-4-(tert-Butoxycarbonyl-methyl-amino)-5-hydroxy-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  Investigation of the Active Site of Aminopeptidase A Using a Series of New Thiol-Containing Inhibitors

  摘要：

  Aminopeptidase A (APA) and aminopeptidase N (APN) are two metallopeptidases which have been suggested to be involved in the enzymatic cascade of the renin-angiotensin system. APA liberates angotensin III from angiotensin II by releasing the N-terminal aspartate, and APN participates in the inactivation of angiotensin III. As the role of angiotensin III in the regulation of blood pressure in the central nervous system and at the periphery is controversial, it was of interest to develop selective and efficient inhibitors of APA. Starting from Glu-thiol,(1) which was the first efficient APA inhibitor described, but however is equipotent on APA (K-i = 0.14 mu M) and APN (K-i = 0.12 mu M), beta-amino thiols bearing various carboxyalkyl chains have been synthesized and their inhibitory potencies measured on both purified enzymes. Compounds containing a carboxylated aromatic ring inhibited APA and APN with K-i values in the micromolar range but were slightly more active on APA. Conversely, inhibitors containing a cyclohexyl ring were more efficient on APN. Various modifications of the structure of Glu-thiol decreased inhibitory activity on both enzymes but increased the selectivity for APA, and compound 9d ((S)-4-amino-6-mercaptohexanoic acid) was 23 times more potent on APA (K-i = 2.0 mu M) than on APN (K-i = 45 mu M).

  DOI：

  10.1021/jm00035a014