5-(2-pivalamidoethyl)-1,2,4-benzenetriol | 155592-12-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 5-(2-pivalamidoethyl)-1,2,4-benzenetriol
• 英文别名: N-(2,4,5-trihydroxyphenethyl)pivalamide；2,2-dimethyl-N-[2-(2,4,5-trihydroxyphenyl)ethyl]propanamide
• CAS: 155592-12-4
• 化学式: C₁₃H₁₉NO₄
• 分子量: 253.298
• InChiKey: OYQVJXMDMJFWET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(2-pivalamidoethyl)-1,2,4-benzenetriol 在 氨 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 4-amino-6-(2-pivalamidoethyl)resorcinol
  参考文献：
  名称：

  Model Reactions for the Quinone-Containing Copper Amine Oxidases. Anaerobic Reaction Pathways and Catalytic Aerobic Deamination of Activated Amines in Buffered Aqueous Acetonitrile

  摘要：

  The quinone form 2 of the N-pivaloyl derivative of 6-hydroxydopamine, developed as a model for the quinone form of the peptidyl 2,4,5-trihydroxyphenylalanine (TOPA) cofactor of the copper amine oxidases, is an effective catalyst for aerobic oxidative deamination of activated amines (e.g., benzylamine and cinnamylamine) in buffered aqueous acetonitrile. The reaction efficiency increases at higher pH and exceeds six turnovers for benzylamine at pH 10, where an apparent alpha-C deuterium kinetic isotope effect of 10 is observed. The yield is limited by the eventual conversion of 2 to the corresponding benzoxazoles (confirming nucleophilic attack of amine at the most electrophilic C-5 carbonyl) and other forms which are incapable of oxidative recycling. Copper(II) inhibits the reaction, in contrast to the free TOPA amino acid, which deaminates benzylamine only when Cu(II) is present. Under anaerobic ''single turnover'' conditions, the products of catalyst reduction are (alkylamino)resorcinols formed via redox cycling reactions of the initial reduced cofactor (either benzenehiol or aminoresorcinol) in the presence of excess amine. Unactivated amines exhibit low deaminative turnover and at high concentrations effect side-chain cleavage of the quinone catalyst induced by C-l Michael addition of amine to the intermediate N-alkyl quinone imines.

  DOI：

  10.1021/ja00116a014
• 作为产物：
  描述：

  2,4,5-tris(benzyloxy)phenetylamine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醚 、 乙醇 为溶剂， 25.0~40.0 ℃ 、413.69 kPa 条件下， 反应 4.0h， 生成 5-(2-pivalamidoethyl)-1,2,4-benzenetriol
  参考文献：
  名称：

  Synthesis and Characterization of Models for the 2,4,5-Trihydroxyphenylalanine (TOPA)-Derived Cofactor of Mammalian Copper Amine Oxidases, and Initial Amine Reactivity Studies

  摘要：

  The mammalian copper amine oxidases effect the oxidative deamination of primary amines through utilization of an ''active carbonyl'' cofactor, shown recently to be the quinone form (TPQ) of a protein-based 2,4,5-trihydroxyphenylalanine (TOPA) residue. We synthesized three models for the cofactor in both reduced (benzenetriol) and oxidized (hydroxyquinone) forms, which differ in the nature of the alkyl substituent mimicking the connection to the protein backbone: hydantoinylmethyl, phthalimidoethyl, and pivalamidoethyl. The quinone forms were capable of deaminating benzylamine in aqueous CH3CN both stoichiometrically and catalytically (in the presence of O-2), but incapable of deaminating non-benzylic amines. In order to clarify the various reactions potentially occurring during aerobic autorecycling deamination, we studied the pH-dependent benzenetriol --> hydroxyquinone autoxidation as well as the possible reaction of amines with the benzenetriol forms. The latter undergo stoichiometric substitution with amines to give (alkylamino)resorcinols, not via cyclohexadienone tautomerization previously proposed, but via a redox cycling mechanism involving condensation of the amines with traces of hydroxyquinone present in the benzenetriol preparations. This observed substitution regiochemistry, as well as structural characterization of the hydroxyquinone arylhydrazine derivatives, confirms that amines react exclusively at the electrophilic C5 carbonyl position of TPQ models. Both the hydroxyquinone and benzenetriol forms were found to react with ethylenediamine in the presence of O-2 to give 6-hydroxy-7-(2-pivalamidoethyl)quinoxaline, consistent with the postulated generation of such moiety when lysyl oxidase is inactivated by ethylenediamine.

  DOI：

  10.1021/jo00088a023

文献信息

• 3-Pyrrolines Are Mechanism-Based Inactivators of the Quinone-Dependent Amine Oxidases but Only Substrates of the Flavin-Dependent Amine Oxidases
  作者：Younghee Lee、Ke-Qing Ling、Xingliang Lu、Richard B. Silverman、E. M. Shepard、D. M. Dooley、Lawrence M. Sayre

  DOI：10.1021/ja0205434

  日期：2002.10.1

  previously reported that 3-pyrroline and 3-phenyl-3-pyrroline effect a time-dependent inactivation of the copper-containing quinone-dependent amine oxidase from bovine plasma (BPAO) (Lee et al. J. Am. Chem. Soc. 1996, 118, 7241-7242). Quinone cofactor model studies suggested a mechanism involving stoichiometric turnover to a stable pyrrolylated cofactor. Full details of the model studies are now reported

  我们之前曾报道过，3-吡咯啉和 3-苯基-3-吡咯啉会影响牛血浆中含铜醌依赖性胺氧化酶 (BPAO) 的时间依赖性失活（Lee 等人，J. Am. Chem. Soc. 1996, 118, 7241-7242)。醌辅因子模型研究表明涉及化学计量转换为稳定的吡咯化辅因子的机制。现在报告了模型研究的全部细节以及 3-芳基-3-吡咯啉（芳基 = 取代苯基、1-萘基、2-萘基）家族对 BPAO 抑制的数据，4-甲氧基-3 -硝基苯基类似物是最有效的。同时，母体 3-苯基类似物是来自牛肝的黄素依赖性线粒体单胺氧化酶 B 的纯底物。对被 4-甲氧基-3-硝基苯基类似物灭活的 BPAO 的光谱研究（包括共振拉曼）与 2,4,5-三羟基苯丙氨酸醌 (TPQ) 辅因子的共价衍生一致。作为一个胺氧化酶家族的灭活剂和另一个胺氧化酶家族的纯底物的一类化合物的区别代表了开发哺乳动物含铜胺氧化酶的选择性抑制剂的独特线索。
• Synthesis and Characterization of Models for the 2,4,5-Trihydroxyphenylalanine (TOPA)-Derived Cofactor of Mammalian Copper Amine Oxidases, and Initial Amine Reactivity Studies
  作者：Fengjiang Wang、Jin-Young Bae、Alan R. Jacobson、Younghee Lee、Lawrence M. Sayre

  DOI：10.1021/jo00088a023

  日期：1994.5

  The mammalian copper amine oxidases effect the oxidative deamination of primary amines through utilization of an ''active carbonyl'' cofactor, shown recently to be the quinone form (TPQ) of a protein-based 2,4,5-trihydroxyphenylalanine (TOPA) residue. We synthesized three models for the cofactor in both reduced (benzenetriol) and oxidized (hydroxyquinone) forms, which differ in the nature of the alkyl substituent mimicking the connection to the protein backbone: hydantoinylmethyl, phthalimidoethyl, and pivalamidoethyl. The quinone forms were capable of deaminating benzylamine in aqueous CH3CN both stoichiometrically and catalytically (in the presence of O-2), but incapable of deaminating non-benzylic amines. In order to clarify the various reactions potentially occurring during aerobic autorecycling deamination, we studied the pH-dependent benzenetriol --> hydroxyquinone autoxidation as well as the possible reaction of amines with the benzenetriol forms. The latter undergo stoichiometric substitution with amines to give (alkylamino)resorcinols, not via cyclohexadienone tautomerization previously proposed, but via a redox cycling mechanism involving condensation of the amines with traces of hydroxyquinone present in the benzenetriol preparations. This observed substitution regiochemistry, as well as structural characterization of the hydroxyquinone arylhydrazine derivatives, confirms that amines react exclusively at the electrophilic C5 carbonyl position of TPQ models. Both the hydroxyquinone and benzenetriol forms were found to react with ethylenediamine in the presence of O-2 to give 6-hydroxy-7-(2-pivalamidoethyl)quinoxaline, consistent with the postulated generation of such moiety when lysyl oxidase is inactivated by ethylenediamine.
• Model Reactions for the Quinone-Containing Copper Amine Oxidases. Anaerobic Reaction Pathways and Catalytic Aerobic Deamination of Activated Amines in Buffered Aqueous Acetonitrile
  作者：Younghee Lee、Lawrence M. Sayre

  DOI：10.1021/ja00116a014

  日期：1995.3

  The quinone form 2 of the N-pivaloyl derivative of 6-hydroxydopamine, developed as a model for the quinone form of the peptidyl 2,4,5-trihydroxyphenylalanine (TOPA) cofactor of the copper amine oxidases, is an effective catalyst for aerobic oxidative deamination of activated amines (e.g., benzylamine and cinnamylamine) in buffered aqueous acetonitrile. The reaction efficiency increases at higher pH and exceeds six turnovers for benzylamine at pH 10, where an apparent alpha-C deuterium kinetic isotope effect of 10 is observed. The yield is limited by the eventual conversion of 2 to the corresponding benzoxazoles (confirming nucleophilic attack of amine at the most electrophilic C-5 carbonyl) and other forms which are incapable of oxidative recycling. Copper(II) inhibits the reaction, in contrast to the free TOPA amino acid, which deaminates benzylamine only when Cu(II) is present. Under anaerobic ''single turnover'' conditions, the products of catalyst reduction are (alkylamino)resorcinols formed via redox cycling reactions of the initial reduced cofactor (either benzenehiol or aminoresorcinol) in the presence of excess amine. Unactivated amines exhibit low deaminative turnover and at high concentrations effect side-chain cleavage of the quinone catalyst induced by C-l Michael addition of amine to the intermediate N-alkyl quinone imines.