methyl (2S)-2-[[(6S,8aR)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-1,2,3,6,7,8-hexahydroindolizine-8a-carbonyl]amino]-3-phenylpropanoate | 189011-59-4

• 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: methyl (2S)-2-[[(6S,8aR)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-1,2,3,6,7,8-hexahydroindolizine-8a-carbonyl]amino]-3-phenylpropanoate
• CAS: 189011-59-4
• 化学式: C₂₄H₃₃N₃O₆
• 分子量: 459.543
• InChiKey: LZFZOBGHUVNTSB-LLJLJFOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-乙酰甘氨酸 、 methyl (2S)-2-[[(6S,8aR)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-1,2,3,6,7,8-hexahydroindolizine-8a-carbonyl]amino]-3-phenylpropanoate 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 生成 (S)-2-{[(6S,8aR)-6-(2-Acetylamino-acetylamino)-5-oxo-hexahydro-indolizine-8a-carbonyl]-amino}-3-phenyl-propionic acid methyl ester
  参考文献：
  名称：

  Peptides Constrained to Type VI β-Turns. 2. Antiparallel β-Ladder Formation

  摘要：

  The preparation and characterization of an extensive series of bis-amino acid conjugates of a novel beta-turn mimic are described. The conjugates were prepared by coupling amino acid residues to the amino and carboxyl groups of the mimic, which represented the central two residues of a peptide constrained to the type VI turn conformation. The resultant adducts had the capability to form either singly or doubly hydrogen-bonded conformations, which represented beta-turn or antiparallel beta-ladder structures, respectively. In the majority of the bis-amino acid conjugates of the cis-lactam 1 (or its enantiomer), only the interior hydrogen bond, characteristic of the singly hydrogen-bonded conformation, was present, according to NMR and IR spectra. When the lactam 1 or its enantiomer were coupled to L-Phe at its carboxyl group and N-AcGly at its amino group, the spectral properties indicated the presence of the doubly hydrogen-bonded form. The results are consistent with other corkers' studies that demonstrated that aryl residues following Pro stabilize antiparallel type VI turn structures and that the propensity of an amino acid to adopt a beta-conformation in proteins is highly dependent on context.

  DOI：

  10.1021/jo961181j
• 作为产物：
  描述：

  (6S,8aR)-6-tert-Butoxycarbonylamino-5-oxo-hexahydro-indolizine-8a-carboxylic acid benzyl ester 在 palladium on activated charcoal 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 methyl (2S)-2-[[(6S,8aR)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-1,2,3,6,7,8-hexahydroindolizine-8a-carbonyl]amino]-3-phenylpropanoate
  参考文献：
  名称：

  限制在VI型β-转位的肽。1.异常稳定的分子内氢键的证据。

  摘要：

  描述了氨基酸与VI型β-转二肽模拟物（1）结合物的合成和构象分析。该模拟物与转弯的中心两个残基具有高度的结构相似性，并且被限制绕四个单键中的两个旋转。氨基酸与模拟物的羧基的偶联提供了能够形成分子内氢键的结合物。在非极性溶剂中，结合物的IR和NMR光谱表明，氨基酸残基的酰胺氢与N端氨基甲酸酯官能团的羰基氢键合，如典型的β转换一样。根据化学位移的温度依赖性，在氢键溶剂DMSO中，分子内氢键仍然存在。我的存在 模拟物1的共轭物中的i + 3氢键由模拟物3的共轭物的光谱特性证实，该分子的分子性质没有证据表明存在分子内氢键。这些研究的结果表明，在没有其他结构约束的情况下，与非氢键键合的VIb构象相比，分子内氢键键合的VIa弯角固有地更稳定。

  DOI：

  10.1021/jo961180r

文献信息

• Peptides Constrained to Type VI β-Turns. 2. Antiparallel β-Ladder Formation
  作者：Kyonghee Kim、Juris P. Germanas

  DOI：10.1021/jo961181j

  日期：1997.5.1

  The preparation and characterization of an extensive series of bis-amino acid conjugates of a novel beta-turn mimic are described. The conjugates were prepared by coupling amino acid residues to the amino and carboxyl groups of the mimic, which represented the central two residues of a peptide constrained to the type VI turn conformation. The resultant adducts had the capability to form either singly or doubly hydrogen-bonded conformations, which represented beta-turn or antiparallel beta-ladder structures, respectively. In the majority of the bis-amino acid conjugates of the cis-lactam 1 (or its enantiomer), only the interior hydrogen bond, characteristic of the singly hydrogen-bonded conformation, was present, according to NMR and IR spectra. When the lactam 1 or its enantiomer were coupled to L-Phe at its carboxyl group and N-AcGly at its amino group, the spectral properties indicated the presence of the doubly hydrogen-bonded form. The results are consistent with other corkers' studies that demonstrated that aryl residues following Pro stabilize antiparallel type VI turn structures and that the propensity of an amino acid to adopt a beta-conformation in proteins is highly dependent on context.
• Peptides Constrained to Type VI β-Turns. 1. Evidence for an Exceptionally Stable Intramolecular Hydrogen Bond
  作者：Kyonghee Kim、Juris P. Germanas

  DOI：10.1021/jo961180r

  日期：1997.5.1

  to the carbonyl group of the N-terminal carbamate functionality, as in typical beta-turns. In the hydrogen-bonding solvent DMSO, the intramolecular hydrogen bond was still present, according to the temperature dependence of the chemical shift. The presence of the i, i + 3 hydrogen bond in the conjugates of mimic 1 was substantiated by the spectral properties of conjugates of the isomeric mimic 3, which

  描述了氨基酸与VI型β-转二肽模拟物（1）结合物的合成和构象分析。该模拟物与转弯的中心两个残基具有高度的结构相似性，并且被限制绕四个单键中的两个旋转。氨基酸与模拟物的羧基的偶联提供了能够形成分子内氢键的结合物。在非极性溶剂中，结合物的IR和NMR光谱表明，氨基酸残基的酰胺氢与N端氨基甲酸酯官能团的羰基氢键合，如典型的β转换一样。根据化学位移的温度依赖性，在氢键溶剂DMSO中，分子内氢键仍然存在。我的存在 模拟物1的共轭物中的i + 3氢键由模拟物3的共轭物的光谱特性证实，该分子的分子性质没有证据表明存在分子内氢键。这些研究的结果表明，在没有其他结构约束的情况下，与非氢键键合的VIb构象相比，分子内氢键键合的VIa弯角固有地更稳定。