(R)-methyl 2-benzyl-2-methylmalonamate | 159835-34-4

• 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-methylmalonamate
• 英文别名: R-(+)-methyl 3-amino-2-benzyl-2-methyl-3-oxopropanoate；methyl (2R)-3-amino-2-benzyl-2-methyl-3-oxopropanoate
• CAS: 159835-34-4
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: GTYCVOYDDAIUDI-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：
  69.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-benzyl-2-methylmalonamate 在 N-甲基吗啉 、 盐酸 、 lithium 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 37.25h， 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：

  2-benzyl-2-methylmalononitrile 在 水 、 双氧水 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (R)-methyl 2-benzyl-2-methylmalonamate
  参考文献：
  名称：

  微生物全细胞催化手性丙二酰胺的脱对称：富含对映体的官能化氨基甲酰乙酸酯的实际合成及其在制备异常α-氨基酸中的应用

  摘要：

  在非常温和的条件下，由含酰胺酶的微生物全细胞催化剂红球菌红球菌AJ270催化，对许多官能化的手性丙二酰胺进行对映选择性去对称化反应，以高产率得到氨基甲酰乙酸，且具有中等至优异的对映选择性。R -（-）-α-烯丙基-α-甲基氨基甲酰乙酸的多克级生物催化制备及其转化成药用目的各种α，α-二取代α-氨基酸的合成应用已得到证明化学。

  DOI：

  10.1016/j.tet.2011.05.103

文献信息

• 2-Benzyl-2-methylsuccinic acid as inhibitor for carboxypeptidase A. synthesis and evaluation
  作者：Mijoon Lee、Yonghao Jin、Dong H. Kim

  DOI：10.1016/s0968-0896(99)00110-8

  日期：1999.8

  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.
• Microbial whole cell-catalyzed desymmetrization of prochiral malonamides: practical synthesis of enantioenriched functionalized carbamoylacetates and their application in the preparation of unusual α-amino acids
  作者：Li-Bin Zhang、De-Xian Wang、Mei-Xiang Wang

  DOI：10.1016/j.tet.2011.05.103

  日期：2011.8

  malonamides underwent enantioselective desymmetrization reaction to afford high yield of carbamoylacetic acids with moderate to excellent enantioselectivity. The synthetic application has been demonstrated with a multi-gram scale biocatalytic preparation of R-(−)-α-allyl-α-methyl-carbamoylacetic acid and its conversions to varied α,α-disubstituted α-amino acids of the interest of medicinal chemistry

  在非常温和的条件下，由含酰胺酶的微生物全细胞催化剂红球菌红球菌AJ270催化，对许多官能化的手性丙二酰胺进行对映选择性去对称化反应，以高产率得到氨基甲酰乙酸，且具有中等至优异的对映选择性。R -（-）-α-烯丙基-α-甲基氨基甲酰乙酸的多克级生物催化制备及其转化成药用目的各种α，α-二取代α-氨基酸的合成应用已得到证明化学。