(R)-methyl 2-acetamido-3-(3,4,5-trimethoxyphenyl)propanoate | 82317-78-0

• 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: (R)-methyl 2-acetamido-3-(3,4,5-trimethoxyphenyl)propanoate
• 英文别名: methyl (2R)-2-acetamido-3-(3,4,5-trimethoxyphenyl)propanoate
• CAS: 82317-78-0
• 化学式: C₁₅H₂₁NO₆
• 分子量: 311.335
• InChiKey: IQKGSVANHBSPPN-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.93
• 重原子数：
  22.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  83.09
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-acetamido-3-(3,4,5-trimethoxyphenyl)propanoate 在 盐酸 、 sodium hydroxide 、 magnesium oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 (R)-2-((tert-butoxycarbonyl)amino)-3-(3,4,5-trimethoxyphenyl)propanoic acid
  参考文献：
  名称：

  Synthesis and biological activity of some very hydrophobic superagonist analogs of luteinizing hormone-releasing hormone

  摘要：

  The effect of increased hydrophobicity at position 6 of luteinizing hormone-releasing hormone (LH-RH) has been investigated by the incorporation of a series of 15 very hydrophobic, unnatural D-amino acids at this position. The unnatural amino acids studied can be considered analogues of phenylalanine with carbocyclic aromatic side chains consisting of substituted phenyl (e.g., 2,4,6-trimethylphenyl, p-biphenyl) or polycyclic aromatic (e.g., naphthalene, anthracene) units. When enzymatic resolution (subtilisin Carlsberg) of the most hydrophobic amino acids failed, the racemic amino acids were incorporated, and the diastereomeric LH-RH analogues were resolved by preparative high-performance liquid chromatography. The analogues were synthesized by the solid-phase technique. All of the synthetic compounds were very potent LH-RH superagonists, but [6-(3-(2-naphthyl)-D-alanine)]LH-RH, [6-(3-(2-naphthyl)-D-alanine), 7-(N alpha-methylleucine)]LH-RH and [6-(3-(2,4,6-trimethylphenyl)-D-alanine)]LH-RH appear to be among the most potent LH-RH agonist analogues yet reported when tested in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds [ED50 approximately 7 x 10(-8) g; twice daily in saline]. These analogues are twice as potent as [D-Trp6,ProNHEt9]LH-RH in this assay system (i.e., approximately 200 times the potency of LH-RH).

  DOI：

  10.1021/jm00349a006
• 作为产物：
  描述：

  N-acetyl-(R,S)-3,4,5-trimethoxyphenylalanine methyl ester 生成 (R)-methyl 2-acetamido-3-(3,4,5-trimethoxyphenyl)propanoate
  参考文献：
  名称：

  Synthesis and biological activity of some very hydrophobic superagonist analogs of luteinizing hormone-releasing hormone

  摘要：

  The effect of increased hydrophobicity at position 6 of luteinizing hormone-releasing hormone (LH-RH) has been investigated by the incorporation of a series of 15 very hydrophobic, unnatural D-amino acids at this position. The unnatural amino acids studied can be considered analogues of phenylalanine with carbocyclic aromatic side chains consisting of substituted phenyl (e.g., 2,4,6-trimethylphenyl, p-biphenyl) or polycyclic aromatic (e.g., naphthalene, anthracene) units. When enzymatic resolution (subtilisin Carlsberg) of the most hydrophobic amino acids failed, the racemic amino acids were incorporated, and the diastereomeric LH-RH analogues were resolved by preparative high-performance liquid chromatography. The analogues were synthesized by the solid-phase technique. All of the synthetic compounds were very potent LH-RH superagonists, but [6-(3-(2-naphthyl)-D-alanine)]LH-RH, [6-(3-(2-naphthyl)-D-alanine), 7-(N alpha-methylleucine)]LH-RH and [6-(3-(2,4,6-trimethylphenyl)-D-alanine)]LH-RH appear to be among the most potent LH-RH agonist analogues yet reported when tested in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds [ED50 approximately 7 x 10(-8) g; twice daily in saline]. These analogues are twice as potent as [D-Trp6,ProNHEt9]LH-RH in this assay system (i.e., approximately 200 times the potency of LH-RH).

  DOI：

  10.1021/jm00349a006

文献信息

• Tailored Peptide Phenyl Esters Block ClpXP Proteolysis by an Unusual Breakdown into a Heptamer–Hexamer Assembly
  作者：Markus Lakemeyer、Eva Bertosin、Friederike Möller、Dóra Balogh、Ralf Strasser、Hendrik Dietz、Stephan A. Sieber

  DOI：10.1002/anie.201901056

  日期：2019.5.20

  binding of probes arrested ClpXP in an unprecedented heptamer–hexamer assembly, in which the two heptameric ClpP rings are dissociated from each other. At the same time, the affinity between ClpX and ClpP increased, leading to inhibition of both enzymes. This conformational arrest is beneficial for the consolidated shutdown of ClpXP, as well as for the study of the oligomeric state during its catalytic

  蛋白水解复合物ClpXP是细菌稳态和发病机理的基础。由于其构象的灵活性，有效的ClpXP抑制剂的开发具有挑战性，迫切需要新的工具来解密其复杂的调控。在这里，我们提出了基于氨基酸的苯基酯作为分子探针，以研究金黄色葡萄球菌的ClpXP复合物的活性和低聚。系统地筛选（R）和（S）氨基酸导致化合物显示出有效的抑制作用，并刺激ClpXP介导的蛋白水解作用。探针的亚化学计量结合使ClpXP停滞在前所未有的七聚体-六聚体组装中，其中两个七聚体ClpP环彼此解离。同时，ClpX和ClpP之间的亲和力增加，导致两种酶的抑制作用。这种构象停滞对于ClpXP的合并关闭以及在其催化循环期间研究低聚状态是有益的。
• Synthesis and biological activity of some very hydrophobic superagonist analogs of luteinizing hormone-releasing hormone
  作者：John J. Nestor、Teresa L. Ho、Richard A. Simpson、Bonnie L. Horner、Gordon H. Jones、Georgia I. McRae、Brian H. Vickery

  DOI：10.1021/jm00349a006

  日期：1982.7

  The effect of increased hydrophobicity at position 6 of luteinizing hormone-releasing hormone (LH-RH) has been investigated by the incorporation of a series of 15 very hydrophobic, unnatural D-amino acids at this position. The unnatural amino acids studied can be considered analogues of phenylalanine with carbocyclic aromatic side chains consisting of substituted phenyl (e.g., 2,4,6-trimethylphenyl, p-biphenyl) or polycyclic aromatic (e.g., naphthalene, anthracene) units. When enzymatic resolution (subtilisin Carlsberg) of the most hydrophobic amino acids failed, the racemic amino acids were incorporated, and the diastereomeric LH-RH analogues were resolved by preparative high-performance liquid chromatography. The analogues were synthesized by the solid-phase technique. All of the synthetic compounds were very potent LH-RH superagonists, but [6-(3-(2-naphthyl)-D-alanine)]LH-RH, [6-(3-(2-naphthyl)-D-alanine), 7-(N alpha-methylleucine)]LH-RH and [6-(3-(2,4,6-trimethylphenyl)-D-alanine)]LH-RH appear to be among the most potent LH-RH agonist analogues yet reported when tested in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds [ED50 approximately 7 x 10(-8) g; twice daily in saline]. These analogues are twice as potent as [D-Trp6,ProNHEt9]LH-RH in this assay system (i.e., approximately 200 times the potency of LH-RH).