(S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-1-diazo-3-phenylbutan-2-one | 171858-42-7

• 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: (S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-1-diazo-3-phenylbutan-2-one
• CAS: 171858-42-7
• 化学式: C₂₃H₃₃N₅O₄
• 分子量: 443.546
• InChiKey: CCTTUTSOAZZQKB-ZJOUEHCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.28
• 重原子数：
  32.0
• 可旋转键数：
  12.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  140.77
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-1-diazo-3-phenylbutan-2-one 在 sodium tetrahydroborate 、 氢溴酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 (2S,3S,11'S,8'S)-3-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-4-phenyl-1-<<7',10'-dioxo-8'-(1-methylpropyl)-2'-oxa-6',9'-diazabicyclo<11.2.2>heptadeca-13',15',16'-trien-11-yl>amino>butan-2-ol
  参考文献：
  名称：

  Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.

  摘要：

  Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-{Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.

  DOI：

  10.1021/ja00146a007
• 作为产物：
  描述：

  Boc-Leu-Val-Phe-OMe 在 N-甲基哌啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.08h， 生成 (S)-2-<<(acetyl)-(S)-leucinyl-(S)-valinyl>amino>-1-diazo-3-phenylbutan-2-one
  参考文献：
  名称：

  Regioselective structural and functional mimicry of peptides. Design of hydrolytically-stable cyclic peptidomimetic inhibitors of HIV-1 protease.

  摘要：

  Hydrolytically-stable cyclic mimetics of the tripeptides Leu-Asn-Phe and Phe-Ile-Val were designed and incorporated into peptidic inhibitors, Ac-{Leu-Asn-Phe}-CHOHCH2-Pro-Ile-Val-NH2 and Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2, of HIV-1 protease. Structural mimicry has been established through molecular modeling and X-ray crystallographic studies of inhibitors bound to HIV-1 protease. Cyclic and acyclic inhibitors had similar conformations that were superimposable and formed similar interactions with the enzyme. Functional mimicry was demonstrated by comparable inhibition of the protease by acyclic and cyclic molecules. Further substitution of the residual acyclic Pro-Ile-Val or Leu-Val-Phe inhibitor components, with Pip-NHtBu or Boc-Phe, respectively, gave hydrolytically stable, water-soluble, lipophilic inhibitors of similar potency. The use of cycles to fix the conformations of amino acid sequences in peptides allows regioselective structural mimicry leading to functional mimicry and also permits localized structure-activity optimization in inhibitors of HIV-1 protease. This approach might be usefully applied to inhibitors of other proteins.

  DOI：

  10.1021/ja00146a007