diethyl (2R,3S)-3-isopropylmalate | 155976-40-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: diethyl (2R,3S)-3-isopropylmalate
• 英文别名: diethyl (2R,3S)-2-hydroxy-3-propan-2-ylbutanedioate
• CAS: 155976-40-2
• 化学式: C₁₁H₂₀O₅
• 分子量: 232.277
• InChiKey: MYKUIPJTFRFCRV-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (2R,3S)-3-isopropylmalate 在 盐酸 作用下， 反应 6.0h， 以82%的产率得到(2R,3S)-3-isopropylmalic acid
  参考文献：
  名称：

  Kinetic Mechanism and Reaction Pathway of Thermus thermophilus Isopropylmalate Dehydrogenase

  摘要：

  Mechanistic studies of isopropylmalate dehydrogenase (IMDH, EC 1.1.1.85),the penultimate enzyme in leucine biosynthesis in bacteria and yeast, have been conducted. It performs two chemical operations, oxidation and decarboxylation, on isopropylmalate to produce alpha-ketoisocaproate. A recombinant enzyme encoded by the leuB gene of the thermophilic bacterium T. thermophilus was used for experiments addressing the kinetic mechanism and chemical pathway of IMDH. A new, asymmetric synthesis of the substrate, (2R,3S)-isopropylmalate, has been developed starting from (2R,3R)tartaric acid. On the basis of kinetic inhibition patterns and exchange experiments, it has been shown that the enzyme follows an ordered sequential bi-tri mechanism, with cofactor NAD binding before substrate beta-isopropylmalate. The release of products occurs in the order CO2, alpha-ketoisocaproate, and NADH. The enzyme catalyzes the exchange of solvent protons into the cu-position of the product, implying that an enol/enolate intermediate is formed. The enzyme conducts two discrete steps: dehydrogenation to isopropyloxaloacetate, which was prepared and shown to be a competent substrate, and decarboxylation to give product.

  DOI：

  10.1021/jo00088a025
• 作为产物：
  描述：

  diethyl (2R,3S)-2-<(3',5'-dinitrobenzoyl)oxy>-3-isopropylsuccinate 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以95%的产率得到diethyl (2R,3S)-3-isopropylmalate
  参考文献：
  名称：

  Kinetic Mechanism and Reaction Pathway of Thermus thermophilus Isopropylmalate Dehydrogenase

  摘要：

  Mechanistic studies of isopropylmalate dehydrogenase (IMDH, EC 1.1.1.85),the penultimate enzyme in leucine biosynthesis in bacteria and yeast, have been conducted. It performs two chemical operations, oxidation and decarboxylation, on isopropylmalate to produce alpha-ketoisocaproate. A recombinant enzyme encoded by the leuB gene of the thermophilic bacterium T. thermophilus was used for experiments addressing the kinetic mechanism and chemical pathway of IMDH. A new, asymmetric synthesis of the substrate, (2R,3S)-isopropylmalate, has been developed starting from (2R,3R)tartaric acid. On the basis of kinetic inhibition patterns and exchange experiments, it has been shown that the enzyme follows an ordered sequential bi-tri mechanism, with cofactor NAD binding before substrate beta-isopropylmalate. The release of products occurs in the order CO2, alpha-ketoisocaproate, and NADH. The enzyme catalyzes the exchange of solvent protons into the cu-position of the product, implying that an enol/enolate intermediate is formed. The enzyme conducts two discrete steps: dehydrogenation to isopropyloxaloacetate, which was prepared and shown to be a competent substrate, and decarboxylation to give product.

  DOI：

  10.1021/jo00088a025

文献信息

• Kinetic Mechanism and Reaction Pathway of Thermus thermophilus Isopropylmalate Dehydrogenase
  作者：Michael C. Pirrung、Hyunsoo Han、David S. Nunn

  DOI：10.1021/jo00088a025

  日期：1994.5

  Mechanistic studies of isopropylmalate dehydrogenase (IMDH, EC 1.1.1.85),the penultimate enzyme in leucine biosynthesis in bacteria and yeast, have been conducted. It performs two chemical operations, oxidation and decarboxylation, on isopropylmalate to produce alpha-ketoisocaproate. A recombinant enzyme encoded by the leuB gene of the thermophilic bacterium T. thermophilus was used for experiments addressing the kinetic mechanism and chemical pathway of IMDH. A new, asymmetric synthesis of the substrate, (2R,3S)-isopropylmalate, has been developed starting from (2R,3R)tartaric acid. On the basis of kinetic inhibition patterns and exchange experiments, it has been shown that the enzyme follows an ordered sequential bi-tri mechanism, with cofactor NAD binding before substrate beta-isopropylmalate. The release of products occurs in the order CO2, alpha-ketoisocaproate, and NADH. The enzyme catalyzes the exchange of solvent protons into the cu-position of the product, implying that an enol/enolate intermediate is formed. The enzyme conducts two discrete steps: dehydrogenation to isopropyloxaloacetate, which was prepared and shown to be a competent substrate, and decarboxylation to give product.