methyl (2R)-2-[(2S)-oxiran-2-yl]-3-phenylpropanoate | 201669-76-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (2R)-2-[(2S)-oxiran-2-yl]-3-phenylpropanoate
• CAS: 201669-76-3
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: JLQDDBTZSAHWHO-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-[(2S)-oxiran-2-yl]-3-phenylpropanoate 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 乙腈 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 2.0h， 生成
  参考文献：
  名称：

  Hydrogen Bonding and Attenuation of the Rate of Enzymic Catalysis

  摘要：

  Hydrogen bonds between a small molecule and an enzyme can potentially contribute significantly to the stability of the complex. Such electrostatic interactions can also lower energy barriers for reactions by solvation of high-energy species. A novel type bf inhibitor is described in this report, which was designed to take advantage of a hydrogen bond that it makes to the active-site histidine of chymotrypsin to attenuate its basicity. Substrates of chymotrypsin acylate the active-site serine (of the catalytic triad), and the acyl-enzyme intermediate undergoes deacylation in a second step of the catalytic turnover. The active-site histidine (of the catalytic triad) serves as the general base in both steps of the turnover process. Such attenuation of basicity by hydrogen bonding was expected to impair catalysis by the enzyme. Two molecules of this type were synthesized that are based on the structure of the chymotrypsin substrate Ac-L-Ala-L-Ala-Gly-L-Phe methyl ester. These were methyl (2R,3R)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (1) and methyl (2R,3S)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (2). Compound 1 acylated chymotrypsin, but the acyl-enzyme species resisted deacylation. On the other hand, compound 2 did not even have the ability to acylate the active-site serine. Molecular modeling supported the assertion that compound 1 makes a critical hydrogen bond to the active-site histidine at the acyl-enzyme stage, whereas compound 2 does so at the preacylation complex. The concepts described herein are of general interest and should find applications for inhibition of enzymes that employ general acid-base chemistry for their catalytic processes.

  DOI：

  10.1021/ja983063e
• 作为产物：
  描述：

  在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 methyl (2R)-2-[(2S)-oxiran-2-yl]-3-phenylpropanoate
  参考文献：
  名称：

  Hydrogen Bonding and Attenuation of the Rate of Enzymic Catalysis

  摘要：

  Hydrogen bonds between a small molecule and an enzyme can potentially contribute significantly to the stability of the complex. Such electrostatic interactions can also lower energy barriers for reactions by solvation of high-energy species. A novel type bf inhibitor is described in this report, which was designed to take advantage of a hydrogen bond that it makes to the active-site histidine of chymotrypsin to attenuate its basicity. Substrates of chymotrypsin acylate the active-site serine (of the catalytic triad), and the acyl-enzyme intermediate undergoes deacylation in a second step of the catalytic turnover. The active-site histidine (of the catalytic triad) serves as the general base in both steps of the turnover process. Such attenuation of basicity by hydrogen bonding was expected to impair catalysis by the enzyme. Two molecules of this type were synthesized that are based on the structure of the chymotrypsin substrate Ac-L-Ala-L-Ala-Gly-L-Phe methyl ester. These were methyl (2R,3R)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (1) and methyl (2R,3S)-5-(N-acetyl-L-alanyl-L-alanyl)amino-2-benzyl-3-hydroxylpentanoate (2). Compound 1 acylated chymotrypsin, but the acyl-enzyme species resisted deacylation. On the other hand, compound 2 did not even have the ability to acylate the active-site serine. Molecular modeling supported the assertion that compound 1 makes a critical hydrogen bond to the active-site histidine at the acyl-enzyme stage, whereas compound 2 does so at the preacylation complex. The concepts described herein are of general interest and should find applications for inhibition of enzymes that employ general acid-base chemistry for their catalytic processes.

  DOI：

  10.1021/ja983063e