(S)-1-{(S)-2-[((2R,3R)-3-Ethoxycarbonyl-oxiranecarbonyl)-amino]-4-methyl-pentanoyl}-pyrrolidine-2-carboxylic acid tert-butyl ester | 199452-12-5

• 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)-1-{(S)-2-[((2R,3R)-3-Ethoxycarbonyl-oxiranecarbonyl)-amino]-4-methyl-pentanoyl}-pyrrolidine-2-carboxylic acid tert-butyl ester
• CAS: 199452-12-5
• 化学式: C₂₁H₃₄N₂O₇
• 分子量: 426.51
• InChiKey: RAEDOPIQIZJDSO-CAOSSQGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.18
• 重原子数：
  30.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  114.54
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (S)-1-{(S)-2-[((2R,3R)-3-Ethoxycarbonyl-oxiranecarbonyl)-amino]-4-methyl-pentanoyl}-pyrrolidine-2-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以90%的产率得到(2S)-1-[(2S)-2-[[(2R,3R)-3-ethoxycarbonyloxirane-2-carbonyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  E-64 analogues as inhibitors of cathepsin B. On the role of the absolute configuration of the epoxysuccinyl group

  摘要：

  A series of trans-epoxysuccinyl-peptide derivatives based on the natural inhibitor E-64 were synthesized in the (2R,3R) and (2S,3S) configuration in order to analyze the role of the stereochemistry of this residue in dictating inhibitory potency and selectivity for cysteine proteases. We confirmed that binding of E-64 like trans-epoxysuccinyl compounds is remarkably favored by the (2S,3S) con figuration, but we also found that CA030-type compounds are stronger inhibitors in the (2R,3R) configuration than the related diastereomers. Consequently, the structural requirements for exploiting both the S and S' subsites are not additive and a structure-based design of bis-peptidyl derivatives of trans-epoxysuccinic acid to increase selective inhibition becomes even more difficult. Additional contrasting effects were observed for the pH optima required in the electrostatic interactions at the S and S' subsites. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00105-3
• 作为产物：
  描述：

  Cbz-L-亮氨酸N-羟基琥珀酰亚胺脂 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (S)-1-{(S)-2-[((2R,3R)-3-Ethoxycarbonyl-oxiranecarbonyl)-amino]-4-methyl-pentanoyl}-pyrrolidine-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  E-64 analogues as inhibitors of cathepsin B. On the role of the absolute configuration of the epoxysuccinyl group

  摘要：

  A series of trans-epoxysuccinyl-peptide derivatives based on the natural inhibitor E-64 were synthesized in the (2R,3R) and (2S,3S) configuration in order to analyze the role of the stereochemistry of this residue in dictating inhibitory potency and selectivity for cysteine proteases. We confirmed that binding of E-64 like trans-epoxysuccinyl compounds is remarkably favored by the (2S,3S) con figuration, but we also found that CA030-type compounds are stronger inhibitors in the (2R,3R) configuration than the related diastereomers. Consequently, the structural requirements for exploiting both the S and S' subsites are not additive and a structure-based design of bis-peptidyl derivatives of trans-epoxysuccinic acid to increase selective inhibition becomes even more difficult. Additional contrasting effects were observed for the pH optima required in the electrostatic interactions at the S and S' subsites. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00105-3