L-pyroglutamyl-L-histidyl-cis-4-hydroxy-L-prolinamide | 136734-86-6

• 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: L-pyroglutamyl-L-histidyl-cis-4-hydroxy-L-prolinamide
• 英文别名: L-pyroglutamyl-L-histydyl-cis-4-hydroxy-L-prolinamide；L-Glp-L-His-L-cHyp-NH2；H-Pyr-His-aHyp-NH2；(2S,4S)-4-hydroxy-1-[(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carboxamide
• CAS: 136734-86-6
• 化学式: C₁₆H₂₂N₆O₅
• 分子量: 378.388
• InChiKey: TYJPWOHEKZWVJM-BJDJZHNGSA-N

物化性质

• 沸点：
  1039.8±65.0 °C(Predicted)
• 密度：
  1.502±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  171
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  L-pyroglutamyl-L-histydyl(Nim-trityl)-cis-4-hydroxy-L-proline 在 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 L-pyroglutamyl-L-histidyl-cis-4-hydroxy-L-prolinamide
  参考文献：
  名称：

  Solid-Phase Synthesis and Spectroscopic Studies of TRH Analogues Incorporating cis- and trans-4-Hydroxy-L-Proline.

  摘要：

  An efficient solid-phase synthesis of the TRH analogue Glp-His(N(im)-Trt)-Hyp-OH is described. N-alpha-Fmoc protected amino acids and DCC/HOBt activation were employed. The bulky and mild-acid-sensitive 2-chlorotrityl resin, utilised as the solid support, completely suppressed dioxopiperazine formation. The tripeptide is a key intermediate in the synthesis of TRH analogues incorporating cis- and trans-4-hydroxy-L-proline. The tripeptide was converted, with inversion of configuration at C-4 of the Hyp residue, to Glp-His(N(im)-Trt)-cHyp lactone in the presence of triphenylphosphine-diethyl azodicarboxylate (TPP-DEAD). One-pot MeOH-TPP-DEAD transesterification of the lactone, followed by N(im)-detritylation, provided Glp-His-cHyp-OMe. This ester gave the corresponding amide and acid on ammonolysis and saponification, respectively. A high-field H-1 NMR investigation of Glp-His-cHyp-OH and its diastereomer Glp-His-Hyp-OH, obtained by N(im)-detritylation of the key tripeptide, showed that the configuration at C-4 of the prolyl residues is critical for the determination of the preferred three-dimensional structure of the molecules.

  DOI：

  10.3891/acta.chem.scand.45-1047

文献信息

• Papaioannou, Dionissios; Athanassopoulos, Constantinos; Magafa, Vassiliki, Acta Chemica Scandinavica, 1995, vol. 49, # 2, p. 103 - 114
  作者：Papaioannou, Dionissios、Athanassopoulos, Constantinos、Magafa, Vassiliki、Karigiannis, George、Karamanos, Nikos、et al.

  DOI：——

  日期：——
• Solid-Phase Synthesis and Spectroscopic Studies of TRH Analogues Incorporating cis- and trans-4-Hydroxy-L-Proline.
  作者：George Stavropoulos、Kostas Karagiannis、Dimitrios Vynios、Dionissios Papaioannou、Dagfinn W. Aksnes、Nils Åge Frøystein、George W. Francis、Britt Karlsson

  DOI：10.3891/acta.chem.scand.45-1047

  日期：——

  An efficient solid-phase synthesis of the TRH analogue Glp-His(N(im)-Trt)-Hyp-OH is described. N-alpha-Fmoc protected amino acids and DCC/HOBt activation were employed. The bulky and mild-acid-sensitive 2-chlorotrityl resin, utilised as the solid support, completely suppressed dioxopiperazine formation. The tripeptide is a key intermediate in the synthesis of TRH analogues incorporating cis- and trans-4-hydroxy-L-proline. The tripeptide was converted, with inversion of configuration at C-4 of the Hyp residue, to Glp-His(N(im)-Trt)-cHyp lactone in the presence of triphenylphosphine-diethyl azodicarboxylate (TPP-DEAD). One-pot MeOH-TPP-DEAD transesterification of the lactone, followed by N(im)-detritylation, provided Glp-His-cHyp-OMe. This ester gave the corresponding amide and acid on ammonolysis and saponification, respectively. A high-field H-1 NMR investigation of Glp-His-cHyp-OH and its diastereomer Glp-His-Hyp-OH, obtained by N(im)-detritylation of the key tripeptide, showed that the configuration at C-4 of the prolyl residues is critical for the determination of the preferred three-dimensional structure of the molecules.