(R)-2-苄基-2-甲基丙二酸单甲酯 | 98061-14-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 中文名称: (R)-2-苄基-2-甲基丙二酸单甲酯
• 英文名称: (R)-2-benzyl-2-methylpropanedioic acid monomethyl ester
• 英文别名: (R)-benzylmethylpropanedioic acid monomethyl ester；(R)-2-benzyl-2-methylmalonic acid monomethyl ester；(2R)-2-benzyl-3-methoxy-2-methyl-3-oxopropanoic acid
• CAS: 98061-14-4
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: UUVYQJWFCVSMFP-GFCCVEGCSA-N

物化性质

• 沸点：
  349.9±30.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-2-苄基-2-甲基丙二酸单甲酯 在 N-甲基吗啉 、 盐酸 、 lithium hydroxide 、 ammonium hydroxide 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 39.5h， 生成 methyl (S)-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
• 作为产物：
  描述：

  benzylmethylpropanedioic acid dimethyl ester 生成 (R)-2-苄基-2-甲基丙二酸单甲酯
  参考文献：
  名称：

  HULT, KARL;BOUTELJE, JOHN;GATENBECK, STEN;NORIN, TORBJORN;BJORKLING, FRED+

  摘要：

  DOI：

文献信息

• Enzyme catalysed hydrolysis of dialkylated propanedioic acid diesters, chain length dependent reversal of enantioselectivity
  作者：Fredrik Björkling、John Boutelje、Sten Gatenbeck、Karl Hult、Torbjŏrn Norin、Peter Szmulik

  DOI：10.1016/s0040-4020(01)96536-6

  日期：1985.1

  Enzyme catalysed hydrolyses of dialkylated propanedioic acid diesters have been studied. A novel change of enantioselectivity from pro-S to pro-R in the hydrolysis of ester groups was observed, depending on the chain length of the alkyl substituents of the substrate. Optically pure (S)-(-)-α-methylphenylalanine was prepared by α-chymotrypsin catalysed hydrolysis of benzylmethylpropanedioic acid dimethyl

  已经研究了二烷基化丙二酸二酯的酶催化水解。观察到在酯基水解中从前-S到前-R的对映选择性的新变化，这取决于底物的烷基取代基的链长。通过α-胰凝乳蛋白酶催化的苄基甲基丙二酸二甲酯的水解制备光学纯的（S）-（-）-α-甲基苯基丙氨酸。
• An ESI-MS Method to Determine Yield and Enantioselectivity in a Single Assay
  作者：Maureen E. Smith、Steven A. Knolls、MyLe Thompson、Douglas S. Masterson

  DOI：10.1007/s13361-014-1041-6

  日期：2015.3.1

  A mass spectrometry assay is presented here that allows for the simultaneous determination of yield and enantioselectivity in a single analysis. The assay makes use of molecules that are structurally similar to the analytes of interest as standards. The assay predicts the yields of the reactions reasonably well and with little error. For example, in the pig liver esterase catalyzed hydrolysis of one prochiral malonate, the yield predicted by the assay was 72%, while larger scale isolated reaction yields were within 5% of this value. This assay provides a fast method to determine yield and enantioselectivity in one analysis. The strengths and limitations of this method are discussed.

  这里提出了一种质谱分析方法，可以在单次分析中同时测定产率和对映选择性。该测定利用结构与目标分析物相似的分子作为标准。该测定相当好地预测了反应的产率并且误差很小。例如，在猪肝酯酶催化水解一种前手性丙二酸中，测定预测的产率为72%，而更大规模的分离反应产率在该值的5%以内。该测定提供了一种在一次分析中确定产量和对映选择性的快速方法。讨论了该方法的优点和局限性。
• 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.
• BJOERKLING, F.;BOUTELJE, J.;GATENBECK, S.;HULT, K.;NORIN, T.;SZMULI, P., TETRAHEDRON, 1985, 41, N 7, 1347-1352
  作者：BJOERKLING, F.、BOUTELJE, J.、GATENBECK, S.、HULT, K.、NORIN, T.、SZMULI, P.

  DOI：——

  日期：——