(2S,3S)-2-{(S)-4-Benzyloxycarbonyl-2-[(S)-4-benzyloxycarbonyl-2-({(1R,2R,3R)-2-[4-(bis-benzyloxy-phosphoryloxy)-phenyl]-3-dimethylcarbamoyl-cyclopropanecarbonyl}-amino)-butyrylamino]-butyrylamino}-3-methyl-pentanoic acid benzyl ester | 397883-70-4

• 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: (2S,3S)-2-{(S)-4-Benzyloxycarbonyl-2-[(S)-4-benzyloxycarbonyl-2-({(1R,2R,3R)-2-[4-(bis-benzyloxy-phosphoryloxy)-phenyl]-3-dimethylcarbamoyl-cyclopropanecarbonyl}-amino)-butyrylamino]-butyrylamino}-3-methyl-pentanoic acid benzyl ester
• CAS: 397883-70-4
• 化学式: C₆₄H₇₁N₄O₁₄P
• 分子量: 1151.26
• InChiKey: PEFKTFMCXTWENZ-NXDDAEMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.32
• 重原子数：
  83.0
• 可旋转键数：
  31.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  231.27
• 氢给体数：
  3.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-{(S)-4-Benzyloxycarbonyl-2-[(S)-4-benzyloxycarbonyl-2-({(1R,2R,3R)-2-[4-(bis-benzyloxy-phosphoryloxy)-phenyl]-3-dimethylcarbamoyl-cyclopropanecarbonyl}-amino)-butyrylamino]-butyrylamino}-3-methyl-pentanoic acid benzyl ester 在 palladium on activated charcoal 水 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以100%的产率得到(2S,3S)-2-[(S)-4-Carboxy-2-((S)-4-carboxy-2-{[(1R,2R,3R)-2-dimethylcarbamoyl-3-(4-phosphonooxy-phenyl)-cyclopropanecarbonyl]-amino}-butyrylamino)-butyrylamino]-3-methyl-pentanoic acid
  参考文献：
  名称：

  Calorimetric and Structural Studies of 1,2,3-Trisubstituted Cyclopropanes as Conformationally Constrained Peptide Inhibitors of Src SH2 Domain Binding

  摘要：

  Isothermal titration calorimetry and X-ray crystallography have been used to determine the structural and thermodynamic consequences associated with constraining the pTyr residue of the pYEE ligand for the Src Homology 2 domain of the Src kinase (Src SH2 domain). The conformation ally constrained peptide mimics that were used are cyclopropane-derived isosteres whereby a cyclopropane ring substitutes to the N-Ca-Cbeta atoms of the phosphotyrosine. Comparison of the thermodynamic data for the binding of the conformationally constrained peptide mimics relative to their equivalent flexible analogues as well as a native tetrapeptide revealed an entropic advantage of 5-9 cal mol(-1) K-1 for the binding of the conformationally constrained ligands. However, an unexpected drop in enthalpy for the binding of the conformationally constrained ligands relative to their flexible analogues was also observed. To evaluate whether these differences reflected conformational variations in peptide binding modes, we have determined the crystal structure of a complex of the Src SH2 domain bound to one of the conformationally constrained peptide mimics. Comparison of this new structure with that of the Src SH2 domain bound to a natural 11-mer peptide (Waksman et al. Cell 1993, 72, 779-790) revealed only very small differences. Hence, cyclopropane-derived peptides are excellent mimics of the bound state of their flexible analogues. However, a rigorous analysis of the structures and of the surface areas at the binding interface, and subsequent computational derivation of the energetic binding parameters, failed to predict the observed differences between the binding thermodynamics of the rigidified and flexible ligands, suggesting that the drop in enthalpy observed with the conformationally constrained peptide mimic arises from sources other than changes in buried surface areas, though the exact origin of the differences remains unclear.

  DOI：

  10.1021/ja011746f
• 作为产物：
  描述：

  (1R)-2-dimethylcarbamoyl-3-(4-hydroxyphenyl)-cyclopropanecarboxylic acid 在 N-甲基吗啉 、 四氮唑 、 叔丁基过氧化氢 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 (2S,3S)-2-{(S)-4-Benzyloxycarbonyl-2-[(S)-4-benzyloxycarbonyl-2-({(1R,2R,3R)-2-[4-(bis-benzyloxy-phosphoryloxy)-phenyl]-3-dimethylcarbamoyl-cyclopropanecarbonyl}-amino)-butyrylamino]-butyrylamino}-3-methyl-pentanoic acid benzyl ester
  参考文献：
  名称：

  Use of 1,2,3-trisubstituted cyclopropanes as conformationally constrained peptide mimics in SH2 antagonists

  摘要：

  Novel conformationally constrained phosphotyrosine pseudopeptide derivatives of the tetrapeptide pY-E-E-I were prepared and evaluated as SH2 binding antagonists. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)01611-7