N-<(2R,3R)-1-<-3-(ethoxycarbonyl)aziridin-2-yl>carbonyl>-(S)-leucyl-(S)-proline benzyl ester | 221345-68-2

• 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: N-<(2R,3R)-1-<-3-(ethoxycarbonyl)aziridin-2-yl>carbonyl>-(S)-leucyl-(S)-proline benzyl ester
• 英文别名: Boc-Phe-D-Azi(CO2Et)-Leu-Pro-OBn；benzyl (2S)-1-[(2S)-2-[[(2R,3R)-3-ethoxycarbonyl-1-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]aziridine-2-carbonyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylate
• CAS: 221345-68-2
• 化学式: C₃₈H₅₀N₄O₉
• 分子量: 706.836
• InChiKey: NYWRDVHTFJNLSN-QENMFVOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  51
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  160
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-<(2R,3R)-1-<-3-(ethoxycarbonyl)aziridin-2-yl>carbonyl>-(S)-leucyl-(S)-proline benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以100%的产率得到(S)-1-((S)-2-{[(2R,3R)-1-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionyl)-3-ethoxycarbonyl-aziridine-2-carbonyl]-amino}-4-methyl-pentanoyl)-pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  aziridinyl peptides as inhibitors of cysteine proteases: Effect of a free carboxylic acid function on inhibition

  摘要：

  Peptides containing aziridine-2,3-dicarboxylate (Azi) as electrophilic building block are evaluated as inhibitors of the cysteine proteases papain, cathepsin B, cathepsin L and clostripain. The influence of a free carboxylic acid as functional group at different positions of the inhibitor molecule on inhibition is analyzed. Structure-activity relationships and binding mode hypotheses are discussed. In contrast to the bacterial enzyme clostripain, the papain like mammalian proteases (cathepsins) are irreversibly inactivated by aziridinyl peptides. N-Unsubstituted aziridines are much more potent inhibitors of papain and cathepsins if they contain the free carboxylic acid attached to the aziridine ring (HOAzi-Leu-ProOBzl). Two free carboxylic acid functions at the aziridine ring are necessary for good inhibition of these enzymes by N'-acylated aziridinyl peptides (BOC-Phe-Azi(OH)(2)). Chimeric bispeptidyl derivatives are selective CB inhibitors if the free acid is located at the C-terminus of the peptide (BOC-Phe-(EtO)Azi-Leu-ProOH). Clostripain is only inhibited by aziridinyl peptide esters. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00058-4
• 作为产物：
  描述：

  2,3-吖丙啶二羧酸,单乙基酯,(2R,3R)-(9CI) 在 palladium on activated charcoal 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 27.25h， 生成 N-<(2R,3R)-1-<-3-(ethoxycarbonyl)aziridin-2-yl>carbonyl>-(S)-leucyl-(S)-proline benzyl ester
  参考文献：
  名称：

  衍生自亲电性α-氨基酸氮丙啶-2,3-二羧酸的新型肽半胱氨酸蛋白酶抑制剂。

  摘要：

  三种不同类型的肽，在其肽链的不同位置上含有氮丙啶-2、3-二羧酸（Azi）作为亲电子的α-氨基酸（I型，N-酰化氮丙啶，Azi作为C末端氨基酸； II型，已合成了以Azi为N末端氨基酸的N-未取代的氮丙啶； III型，Azi的N-酰化双肽基衍生物），并已作为半胱氨酸蛋白酶木瓜蛋白酶，组织蛋白酶B，L和H以及钙蛋白酶I和I的抑制剂进行了测试。 II，以及针对几种丝氨酸蛋白酶，一种天冬氨酸和一种金属蛋白酶。所有的氮丙啶基肽都是特定的半胱氨酸蛋白酶抑制剂。木瓜蛋白酶和组织蛋白酶B和L被不可逆地抑制，而组织蛋白酶H和钙蛋白酶以非时间依赖性方式被抑制。某些化合物被证明是丝氨酸蛋白酶和金属蛋白酶嗜热菌蛋白酶的底物。可以观察到三种不同类型的抑制剂之间的显着差异，包括立体特异性，抑制的pH依赖性，不同的半胱氨酸蛋白酶之间的选择性以及在氮丙啶环上的游离羧酸功能对于抑制的重要性。首先，II型抑制剂是众所周知的

  DOI：

  10.1021/jm981061z

文献信息

• aziridinyl peptides as inhibitors of cysteine proteases: Effect of a free carboxylic acid function on inhibition
  作者：T. Schirmeister、M. Peric

  DOI：10.1016/s0968-0896(00)00058-4

  日期：2000.6

  Peptides containing aziridine-2,3-dicarboxylate (Azi) as electrophilic building block are evaluated as inhibitors of the cysteine proteases papain, cathepsin B, cathepsin L and clostripain. The influence of a free carboxylic acid as functional group at different positions of the inhibitor molecule on inhibition is analyzed. Structure-activity relationships and binding mode hypotheses are discussed. In contrast to the bacterial enzyme clostripain, the papain like mammalian proteases (cathepsins) are irreversibly inactivated by aziridinyl peptides. N-Unsubstituted aziridines are much more potent inhibitors of papain and cathepsins if they contain the free carboxylic acid attached to the aziridine ring (HOAzi-Leu-ProOBzl). Two free carboxylic acid functions at the aziridine ring are necessary for good inhibition of these enzymes by N'-acylated aziridinyl peptides (BOC-Phe-Azi(OH)(2)). Chimeric bispeptidyl derivatives are selective CB inhibitors if the free acid is located at the C-terminus of the peptide (BOC-Phe-(EtO)Azi-Leu-ProOH). Clostripain is only inhibited by aziridinyl peptide esters. (C) 2000 Elsevier Science Ltd. All rights reserved.
• New Peptidic Cysteine Protease Inhibitors Derived from the Electrophilic α-Amino Acid Aziridine-2,3-dicarboxylic Acid
  作者：Tanja Schirmeister

  DOI：10.1021/jm981061z

  日期：1999.2.1

  bispeptidyl derivatives of Azi) have been synthesized and tested as inhibitors of the cysteine proteases papain, cathepsins B, L, and H, and calpains I and II, as well as against several serine proteases, one aspartate, and one metalloprotease. All aziridinyl peptides are specific cysteine protease inhibitors. Papain and cathepsins B and L are inhibited irreversibly, whereas cathepsin H and calpains

  三种不同类型的肽，在其肽链的不同位置上含有氮丙啶-2、3-二羧酸（Azi）作为亲电子的α-氨基酸（I型，N-酰化氮丙啶，Azi作为C末端氨基酸； II型，已合成了以Azi为N末端氨基酸的N-未取代的氮丙啶； III型，Azi的N-酰化双肽基衍生物），并已作为半胱氨酸蛋白酶木瓜蛋白酶，组织蛋白酶B，L和H以及钙蛋白酶I和I的抑制剂进行了测试。 II，以及针对几种丝氨酸蛋白酶，一种天冬氨酸和一种金属蛋白酶。所有的氮丙啶基肽都是特定的半胱氨酸蛋白酶抑制剂。木瓜蛋白酶和组织蛋白酶B和L被不可逆地抑制，而组织蛋白酶H和钙蛋白酶以非时间依赖性方式被抑制。某些化合物被证明是丝氨酸蛋白酶和金属蛋白酶嗜热菌蛋白酶的底物。可以观察到三种不同类型的抑制剂之间的显着差异，包括立体特异性，抑制的pH依赖性，不同的半胱氨酸蛋白酶之间的选择性以及在氮丙啶环上的游离羧酸功能对于抑制的重要性。首先，II型抑制剂是众所周知的