tert-butyl 2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoacetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoacetate
• 英文别名: Tert-butyl 2-[[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-2-oxoacetate
• 化学式: C₁₂H₂₁NO₅
• 分子量: 259.302
• InChiKey: YEWZBCVTWRAKRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoacetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以93.6%的产率得到N-草酰甘氨酸
  参考文献：
  名称：

  O-Alkyl Hydroxamates as Metaphors of Enzyme-Bound Enolate Intermediates in Hydroxy Acid Dehydrogenases. Inhibitors of Isopropylmalate Dehydrogenase, Isocitrate Dehydrogenase, and Tartrate Dehydrogenase¹

  摘要：

  The inhibition of Thermus thermophilus isopropylmalate dehydrogenase by O-methyl oxalohydroxamate was studied for comparison to earlier results of Schloss with the Salmonella enzyme. It is a fairly potent (1.2 mu M), slow-binding, uncompetitive inhibitor against isopropylmalate and is far superior to an oxamide (25 mM K-i competitive) that is isosteric with the ketoisocaproate product of the enzyme. This improvement in inhibition was attributed to its increased NH acidity, which presumably is due to the inductive effect of the hydroxylamine oxygen. This principle was extended to the structurally homologous enzyme isocitrate dehydrogenase from E. coli, for which the compound O-(carboxymethyl) oxalohydroxamate is a 30 nM inhibitor, uncompetitive against isocitrate. The pH dependence of its inhibition supports the idea that it is bound to the enzyme in the anionic form. Another recently discovered homologous enzyme, tartrate dehydrogenase from Pseudomonas putida, was studied with oxalylhydroxamate. It has a relatively low affinity for the enzyme, though it is superior to tartrate. On the basis of these leads, squaric hydroxamates with increased acidity compared to squaric amides directed toward two of these enzymes were prepared, and they also show increased inhibitory potency, though not approaching the nanomolar levels of the oxalylhydroxamates.

  DOI：

  10.1021/jo952090+
• 作为产物：
  描述：

  tert-butyl glyoxylate 在 ammonium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以64%的产率得到tert-butyl 2-((2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoacetate
  参考文献：
  名称：

  发现氧化还原系统使C–N–C键形成：前所未有的Aza-Cannizzaro反应

  摘要：

  描述了涉及乙醛酸酯原位氧化还原转化为甘氨酸的新型反应。简单的原料和合成甘氨酸衍生物的温和条件可能表明了通往益生元化学的途径。该过程类似于涉及氨的坎尼扎罗反应，因此可以称为分子内Aza-Cannizzaro型反应。借助计算分析详细检查了该反应，以证实所提出的机理。

  DOI：

  10.1016/j.tetlet.2017.04.010

文献信息

• <i>O</i>-Alkyl Hydroxamates as Metaphors of Enzyme-Bound Enolate Intermediates in Hydroxy Acid Dehydrogenases. Inhibitors of Isopropylmalate Dehydrogenase, Isocitrate Dehydrogenase, and Tartrate Dehydrogenase¹
  作者：Michael C. Pirrung、Hyunsoo Han、Jrlung Chen

  DOI：10.1021/jo952090+

  日期：1996.1.1

  The inhibition of Thermus thermophilus isopropylmalate dehydrogenase by O-methyl oxalohydroxamate was studied for comparison to earlier results of Schloss with the Salmonella enzyme. It is a fairly potent (1.2 mu M), slow-binding, uncompetitive inhibitor against isopropylmalate and is far superior to an oxamide (25 mM K-i competitive) that is isosteric with the ketoisocaproate product of the enzyme. This improvement in inhibition was attributed to its increased NH acidity, which presumably is due to the inductive effect of the hydroxylamine oxygen. This principle was extended to the structurally homologous enzyme isocitrate dehydrogenase from E. coli, for which the compound O-(carboxymethyl) oxalohydroxamate is a 30 nM inhibitor, uncompetitive against isocitrate. The pH dependence of its inhibition supports the idea that it is bound to the enzyme in the anionic form. Another recently discovered homologous enzyme, tartrate dehydrogenase from Pseudomonas putida, was studied with oxalylhydroxamate. It has a relatively low affinity for the enzyme, though it is superior to tartrate. On the basis of these leads, squaric hydroxamates with increased acidity compared to squaric amides directed toward two of these enzymes were prepared, and they also show increased inhibitory potency, though not approaching the nanomolar levels of the oxalylhydroxamates.
• Discovery of redox system enabling C–N–C bonds formation: Unprecedented Aza-Cannizzaro reaction
  作者：Abhishek Sud、Pramod S. Chaudhari、Ishu Agarwal、Amjad Basha Mohammad、Vilas H. Dahanukar、Rakeshwar Bandichhor

  DOI：10.1016/j.tetlet.2017.04.010

  日期：2017.5

  derivatives probably indicate a pathway towards prebiotic chemistry. This proceeds analogous to Cannizzaro reaction involving ammonia therefore it can be termed as intramolecular Aza-Cannizzaro type reaction. This reaction is examined in detail with an aid of computational analysis to corroborate the proposed mechanism.

  描述了涉及乙醛酸酯原位氧化还原转化为甘氨酸的新型反应。简单的原料和合成甘氨酸衍生物的温和条件可能表明了通往益生元化学的途径。该过程类似于涉及氨的坎尼扎罗反应，因此可以称为分子内Aza-Cannizzaro型反应。借助计算分析详细检查了该反应，以证实所提出的机理。