2-S-Cysteinylepinephrine

• 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: 2-S-Cysteinylepinephrine
• 英文别名: (2R)-2-amino-3-[6-[(1R)-2-amino-1-hydroxyethyl]-2,3-dihydroxyphenyl]sulfanylpropanoic acid
• 化学式: C₁₁H₁₆N₂O₅S
• 分子量: 288.324
• InChiKey: WBFJPWXWFPWDSJ-XPUUQOCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  175
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  去甲肾上腺素 在 盐酸 作用下， 以 水 为溶剂， 反应 0.5h， 生成 2-S-Cysteinylepinephrine
  参考文献：
  名称：

  Oxidative Metabolites of 5-S-Cysteinylnorepinephrine Are Irreversible Inhibitors of Mitochondrial Complex I and the α-Ketoglutarate Dehydrogenase and Pyruvate Dehydrogenase Complexes:  Possible Implications for Neurodegenerative Brain Disorders

  摘要：

  The major initial product of the oxidation of norepinephrine (NE) in the presence of L-cysteine is 5-S-cysteinylnorepinephrine which is then further easily oxidized to the dihydrobenzothiazine (DHBT) 7-(1-hydroxy-2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-NE-1). When incubated with intact rat brain mitochondria, DHBT-NE-1 evokes rapid inhibition of complex I respiration without affecting complex II respiration. DHBT-NE-1 also evokes time- and concentration-dependent irreversible inhibition of NADH-coenzyme Q(1) (CoQ(1)) reductase, the pyruvate dehydrogenase complex (PDHC), and alpha-ketoglutarate dehydrogenase (alpha-KGDH) when incubated with frozen and thawed rat brain mitochondria (mitochondrial membranes). The time dependence of the inhibition of NADH-CoQ(1) reductase, PDHC, and alpha-KGDH by DHBT-NE-1 appears to be related to its oxidation, catalyzed by an unknown component of the inner mitochondrial membrane, to electrophilic intermediates which bind covalently to active site cysteinyl residues of these enzyme complexes. The latter conclusion is based on the ability of glutathione to block inhibition of NADH-CoQ(1) reductase, PDHC, and alpha-KGDH by scavenging electrophilic intermediates, generated by the mitochondrial membrane-catalyzed oxidation of DHBT-NE-1, forming glutathionyl conjugates, several of which have been isolated and spectroscopically identified. The possible implications of these results to the degeneration of neuromelanin-pigmented noradrenergic neurons in the locus ceruleus in Parkinson's disease are discussed.

  DOI：

  10.1021/tx990170t

文献信息

• Oxidation Chemistry of (−)-Norepinephrine in the Presence of <scp>l</scp>-Cysteine
  作者：Xue-Ming Shen、Glenn Dryhurst

  DOI：10.1021/jm960016t

  日期：1996.1.1

  noradrenergic neurotransmitter (-)-norepinephrine (1) is very easily oxidized at physiological pH to an o-quinone (2) that normally cyclizes and subsequently oxidatively polymerizes to black melanin. In this investigation it is demonstrated that L-cysteine (CySH) can divert the melanin pathway by efficiently scavenging o-quinone 2 to give, initially, 5-S-cysteinylnorepinephrine (6) and 2-S-cysteinylnorepinephrine

  去甲肾上腺素能神经递质（-）-去甲肾上腺素（1）在生理pH值下很容易被氧化成邻苯二酚（2），后者通常会环化并随后氧化聚合成黑色素。在这项研究中，证明了L-半胱氨酸（CySH）可以通过有效清除o-醌2最初产生5-S-半胱氨酰去甲肾上腺素（6）和2-S-半胱氨酰去甲肾上腺素（7）来转移黑色素途径。这些半胱氨酰共轭物比1更容易被氧化为邻醌，部分被CySH进一步攻击生成2,5-bi-S-半胱氨酰去甲肾上腺素（8），这是一种更容易氧化的化合物。在6-8氧化后形成的邻醌中间体也可以进行容易的分子内环化反应，生成双环邻醌亚胺，该亚胺氧化半胱氨酰共轭物，它们从它们所衍生的反应序列中首先导致大量的二氢苯并噻嗪。这些化合物中的至少两种，7-（1-羟基-2-氨基乙基）-3,4-二氢-5-羟基-2H-1,4-苯并噻嗪-3-羧酸（9）和8-（1-当将羟基-2-氨基乙基）-3,4-二氢-5-羟基-2H-1、4-苯并噻
• Oxidative Metabolites of 5-<i>S</i>-Cysteinylnorepinephrine Are Irreversible Inhibitors of Mitochondrial Complex I and the α-Ketoglutarate Dehydrogenase and Pyruvate Dehydrogenase Complexes:  Possible Implications for Neurodegenerative Brain Disorders
  作者：Wenkuan Xin、Xue-Ming Shen、Hong Li、Glenn Dryhurst

  DOI：10.1021/tx990170t

  日期：2000.8.1

  The major initial product of the oxidation of norepinephrine (NE) in the presence of L-cysteine is 5-S-cysteinylnorepinephrine which is then further easily oxidized to the dihydrobenzothiazine (DHBT) 7-(1-hydroxy-2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-NE-1). When incubated with intact rat brain mitochondria, DHBT-NE-1 evokes rapid inhibition of complex I respiration without affecting complex II respiration. DHBT-NE-1 also evokes time- and concentration-dependent irreversible inhibition of NADH-coenzyme Q(1) (CoQ(1)) reductase, the pyruvate dehydrogenase complex (PDHC), and alpha-ketoglutarate dehydrogenase (alpha-KGDH) when incubated with frozen and thawed rat brain mitochondria (mitochondrial membranes). The time dependence of the inhibition of NADH-CoQ(1) reductase, PDHC, and alpha-KGDH by DHBT-NE-1 appears to be related to its oxidation, catalyzed by an unknown component of the inner mitochondrial membrane, to electrophilic intermediates which bind covalently to active site cysteinyl residues of these enzyme complexes. The latter conclusion is based on the ability of glutathione to block inhibition of NADH-CoQ(1) reductase, PDHC, and alpha-KGDH by scavenging electrophilic intermediates, generated by the mitochondrial membrane-catalyzed oxidation of DHBT-NE-1, forming glutathionyl conjugates, several of which have been isolated and spectroscopically identified. The possible implications of these results to the degeneration of neuromelanin-pigmented noradrenergic neurons in the locus ceruleus in Parkinson's disease are discussed.