(2S,3S)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutyryl-L-prolyl-methyl ester | 863640-20-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2S,3S)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutyryl-L-prolyl-methyl ester
• 英文别名: (2S,3S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoyl-(S)-proline methyl ester
• CAS: 863640-20-4
• 化学式: C₂₄H₂₈N₂O₆
• 分子量: 440.496
• InChiKey: JBKCHAYPWHUSSO-ACRUOGEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.05
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  105.17
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutyryl-L-prolyl-methyl ester 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 以61%的产率得到methyl (2S)-1-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutanoyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Novel 3-amino-2-hydroxy acids containing protease inhibitors. Part 1: Synthesis and kinetic characterization as aminopeptidase P inhibitors

  摘要：

  Novel, potent inhibitors of aminopeptidase P, containing a 3-amino-2-hydroxy acid and a proline ora proline analogues, have been prepared. One part of the bestatin-derived inhibitors was found to inhibit APP from Excherichia coli and from rat intestine according to a mixed-type mechanism, with K-i values up to 1.26 mu M. The other compounds. 3-amino-2-hydroxy acyl prolines of a different configuration. inhibit APP competitively, according to a slow-binding mechanism, with K-i values in the nanomolar up to the micromolar range. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.040
• 作为产物：
  描述：

  苄基(S)-1-(N-甲氧基-N-甲基氨基甲酰基)-2-苯乙基氨基甲酸酯 在 lithium hydroxide 、 sodium tetrahydroborate 、 叔丁基锂 、 1-羟基苯并三唑 、 臭氧 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 magnesium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.83h， 生成 (2S,3S)-3-(N-benzyloxycarbonyl)amino-2-hydroxy-4-phenylbutyryl-L-prolyl-methyl ester
  参考文献：
  名称：

  Selectivity in the Inhibition of HIV and FIV Protease: Inhibitory and Mechanistic Studies of Pyrrolidine-Containing .alpha.-Keto Amide and Hydroxyethylamine Core Structures

  摘要：

  This paper describes the development of new pyrrolidine-containing alpha-keto amide and hydroxyethylamine core structures as mechanism based inhibitors of the HIV and FIV proteases. It was found that the alpha-keto amide core structure 2 is approximately 300-fold better than the corresponding hydroxyethylamine isosteric structure and 1300-fold better than the corresponding phosphinic acid derivative as an inhibitor of the HIV protease. The alpha-keto amide is however not hydrated until it is bound to the HIV protease as indicated by the NMR study and the X-ray structural analysis. Further analysis of the inhibition activities of hydroxyethylamine isosteres containing modified pyrrolidine derivatives revealed that a cis-methoxy group at C-4 of the pyrrolidine would improve the binding 5-and 25-fold for the trans-isomer. When this strategy was applied to the alpha-keto amide isostere, a cis-benzyl ether at C-4 was found to enhance binding 3-fold. Of the core structures prepared as inhibitors of the HIV protease, none show significant inhibitory activity against the mechanistically identical FIV protease, and additional complementary groups are needed to improve inhibition.

  DOI：

  10.1021/ja00153a008