(R)-methyl 2-benzyl-2-methyl-3-hydroxypropanoate | 247588-13-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-methyl 2-benzyl-2-methyl-3-hydroxypropanoate
• CAS: 247588-13-2
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: ASYOBFJZEUVPFV-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-benzyl-2-methyl-3-hydroxypropanoate 在 咪唑 、 18-冠醚-6 、 碘 、 三苯基膦 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 28.0h， 生成 (R)-methyl 2-benzyl-2-methyl-3-cyanopropanoate
  参考文献：
  名称：

  2-Benzyl-2-methylsuccinic acid as inhibitor for carboxypeptidase A. synthesis and evaluation

  摘要：

  Recently, Asante-Appiah et al. (Asante-Appiah, E.; Seetharaman, J.; Sicheri, F.; Yang, D. S.-C.; Chan, W. W.-C. Biochemistry 1997, 36, 8710-8715) reported that 2-ethyl-2-methylsuccinic acid isa highly potent inhibitor for carboxypeptidase A (CPA), a prototypic zinc protease. The X-ray crystal structure of the complex of the enzyme formed with 2-ethyl-2-methylsuccinic acid revealed that at the active site of CPA there is present a small cavity which accommodates the methyl group of the inhibitor. These investigators postulated that incorporation of a methyl group at the alpha-position to the carboxylate of existing inhibitors of CPA would improve the inhibitory potency. We have synthesized racemic and optically active 2-benzyl-2-methylsuccinic acids and evaluated their inhibitory activities for CPA to find the K-i values to be 0.28, 0.15, and 17 mu M for racemic form, (R)-, and (S)-enantiomer, respectively. Contrary to the expectation, the effect on the binding affinity by the incorporation of the methyl group is minimal. The validity of the proposition that the small cavity may be utilized for the improvement of the inhibitory potency appears questionable. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00110-8
• 作为产物：
  描述：

  (S)-2-Benzyl-3-isobutoxycarbonyloxy-2-methyl-3-oxo-propionic acid methyl ester 在 sodium tetrahydroborate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 1.0h， 以1.67 g的产率得到(R)-methyl 2-benzyl-2-methyl-3-hydroxypropanoate
  参考文献：
  名称：

  2-Benzyl-2-methylsuccinic acid as inhibitor for carboxypeptidase A. synthesis and evaluation

  摘要：

  Recently, Asante-Appiah et al. (Asante-Appiah, E.; Seetharaman, J.; Sicheri, F.; Yang, D. S.-C.; Chan, W. W.-C. Biochemistry 1997, 36, 8710-8715) reported that 2-ethyl-2-methylsuccinic acid isa highly potent inhibitor for carboxypeptidase A (CPA), a prototypic zinc protease. The X-ray crystal structure of the complex of the enzyme formed with 2-ethyl-2-methylsuccinic acid revealed that at the active site of CPA there is present a small cavity which accommodates the methyl group of the inhibitor. These investigators postulated that incorporation of a methyl group at the alpha-position to the carboxylate of existing inhibitors of CPA would improve the inhibitory potency. We have synthesized racemic and optically active 2-benzyl-2-methylsuccinic acids and evaluated their inhibitory activities for CPA to find the K-i values to be 0.28, 0.15, and 17 mu M for racemic form, (R)-, and (S)-enantiomer, respectively. Contrary to the expectation, the effect on the binding affinity by the incorporation of the methyl group is minimal. The validity of the proposition that the small cavity may be utilized for the improvement of the inhibitory potency appears questionable. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00110-8

文献信息

• Syntheses and Kinetic Evaluation of Racemic and Optically Active 2-Benzyl-2-methyl-3,4-epoxybutanoic Acids as Irreversible Inactivators for Carboxypeptidase A
  作者：Mijoon Lee、Dong H. Kim

  DOI：10.1016/s0968-0896(01)00340-6

  日期：2002.4

  Racemic and optically active 2-benzyl-2-methyl-3,4-epoxybutanoic acids were synthesized and evaluated as inactivators for carboxypeptidase A. a representative zinc-containing proteolytic enzyme. Only the threo-form of the inactivator is effective and its potency in terms of k(inact)/K-I value is lower by 42-fold compared with 2-benzyl-3,4-epoxybutanoic acid, indicating that the alpha-methyl group affects adversely in the inactivation contrary to the expectation that it would enhance the inactivation activity of the inhibitor through additional interactions of the methyl group with a small cavity (alpha-methyl hole) present next to the S-1' hydrophobic pocket. Of the enantiomeric pair, the inactivator having the (2S,3R)-configuration is more potent than its enantiomer by 44-fold. The observed kinetic results may be rationalized on the basis that the methyl group in the inactivator having the (2R,3S)configuration experiences the van der Waals repulsive interactions with the bottom of the active site crevice in binding to CPA, casting a doubt on the presence of the so-called alpha-methyl hole at the active site of carboxypeptidase A. (C) 2002 Elsevier Science Ltd. All rights reserved.