1-methyl-1,2,3,4-tetrahydro-β-carboline-5,6-dione | 137743-78-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-methyl-1,2,3,4-tetrahydro-β-carboline-5,6-dione
• 英文别名: 1-Methyl-2,3,4,9-tetrahydro-1H-beta-carboline-5,6-dione；1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-5,6-dione
• CAS: 137743-78-3
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: QLAJIPPQYOXQCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  485.3±45.0 °C(Predicted)
• 密度：
  1.320±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-methyl-1,2,3,4-tetrahydro-β-carboline-5,6-dione 在 phosphate buffer 作用下， 反应 0.67h， 生成 (S)-2-Amino-4-[(R)-1-(carboxymethyl-carbamoyl)-2-(1-methyl-5,6-dioxo-2,3,4,5,6,9-hexahydro-1H-β-carbolin-8-ylsulfanyl)-ethylcarbamoyl]-butyric acid
  参考文献：
  名称：

  Influence of Glutathione on the Oxidation of 1-Methyl-6-hydroxy- 1,2,3,4-tetrahydro-β-carboline:  Chemistry of Potential Relevance to the Addictive and Neurodegenerative Consequences of Ethanol Abuse

  摘要：

  Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetaldehyde, which would react with unbound 5-hydroxytryptamine (5-HT) to give 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1), known to be formed at elevated levels in the brain following ethanol drinking, and HO. necessary to oxidize this alkaloid. In this study, it is demonstrated that the HO.-mediated oxidation of 1 at physiological pH yields 1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (8) that reacts avidly with free glutathione (GSH), a significant constituent of axons and nerve terminals, to give diastereomers of 8-S-glutathionyl-1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (9A and 9B). In the presence of free GSH, ascorbic acid, other intraneuronal antioxidants/reductants, and molecular oxygen diastereomers, 9A/9B redox cycle in reactions that generate H2O2 and, via trace transition metal ion catalyzed decomposition of the latter compound, HO.. Further reactions of 9A/9B with GSH and/or HO. generate several additional glutathioxyl conjugates that also redox cycle in the presence of intraneuronal reductants and molecular oxygen forming H2O2 and HO.. Thus, intraneuronal formation of 1 and HO. as a consequence of ethanol drinking and resultant endogenous synthesis of 8, 9A, and 9B would, based on these in vitro chemical studies, be expected to generate elevated fluxes of H2O2 and HO. leading to oxidative damage to serotonergic axons and nerve terminals and the irreversible loss of GSH, both of which occur in the brain as a consequence of ethanol drinking. Furthermore, deficiencies of 5-HT and loss of certain serotonergic pathways in the brain have been linked to the preference for and addiction to ethanol.

  DOI：

  10.1021/jm9504870
• 作为产物：
  描述：

  5-羟基色胺盐酸盐 在 水 作用下， 以 水 为溶剂， 反应 12.83h， 生成 1-methyl-1,2,3,4-tetrahydro-β-carboline-5,6-dione
  参考文献：
  名称：

  中央哺乳动物生物碱1-甲基-6-羟基-1,2,3,4-四氢-β-咔啉的氧化化学和生物化学。

  摘要：

  已在热解石墨电极（PGE）的中性水溶液中研究了哺乳动物中央生物碱1-甲基-6-羟基-1,2,3,4-四氢-β-咔啉（1）的电化学氧化。1的伏安图显示两个紧密间隔的氧化峰Ia和IIa。在电位小于峰值Ia的峰值电位（Ep）的情况下，1被氧化成自由基中间体，该中间体二聚化得到5,5'-bi（1-methyl-6-hydroxy-1,2,3， 4-四氢-β-咔啉）（5和6）。在比峰1a的电位更强的Ep上，假定的自由基中间体被进一步电氧化为以C（5）为中心的碳正离子，在离子-底物反应中与1反应生成5和6或与水反应生成最终的1-甲基1,2,3,4-四氢-β-咔啉-5,6-二酮（12）。二聚体5和6在PGE处产生两个可逆的氧化峰，第二个对应于在1伏安图中观察到的峰IIa。由于5和6是易于氧化的化合物，因此它们仅在受控电势电氧化的初始阶段被观察到1.酪氨酸酶/ O2，人铜蓝蛋白/ O2和过氧化物酶/ H2

  DOI：

  10.1021/jm00079a010

文献信息

• Influence of Glutathione on the Oxidation of 1-Methyl-6-hydroxy- 1,2,3,4-tetrahydro-β-carboline:  Chemistry of Potential Relevance to the Addictive and Neurodegenerative Consequences of Ethanol Abuse
  作者：Qing-Ping Han、Glenn Dryhurst

  DOI：10.1021/jm9504870

  日期：1996.1.1

  Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetaldehyde, which would react with unbound 5-hydroxytryptamine (5-HT) to give 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1), known to be formed at elevated levels in the brain following ethanol drinking, and HO. necessary to oxidize this alkaloid. In this study, it is demonstrated that the HO.-mediated oxidation of 1 at physiological pH yields 1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (8) that reacts avidly with free glutathione (GSH), a significant constituent of axons and nerve terminals, to give diastereomers of 8-S-glutathionyl-1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (9A and 9B). In the presence of free GSH, ascorbic acid, other intraneuronal antioxidants/reductants, and molecular oxygen diastereomers, 9A/9B redox cycle in reactions that generate H2O2 and, via trace transition metal ion catalyzed decomposition of the latter compound, HO.. Further reactions of 9A/9B with GSH and/or HO. generate several additional glutathioxyl conjugates that also redox cycle in the presence of intraneuronal reductants and molecular oxygen forming H2O2 and HO.. Thus, intraneuronal formation of 1 and HO. as a consequence of ethanol drinking and resultant endogenous synthesis of 8, 9A, and 9B would, based on these in vitro chemical studies, be expected to generate elevated fluxes of H2O2 and HO. leading to oxidative damage to serotonergic axons and nerve terminals and the irreversible loss of GSH, both of which occur in the brain as a consequence of ethanol drinking. Furthermore, deficiencies of 5-HT and loss of certain serotonergic pathways in the brain have been linked to the preference for and addiction to ethanol.
• Oxidation chemistry and biochemistry of the central mammalian alkaloid 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-.beta.-carboline
  作者：Fa Zhang、R. N. Goyal、C. LeRoy Blank、Glenn Dryhurst

  DOI：10.1021/jm00079a010

  日期：1992.1

  The electrochemical oxidation of the central mammalian alkaloid 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1) has been studied in neutral aqueous solution at a pyrolytic graphite electrode (PGE). Voltammograms of 1 show two closely spaced oxidation peaks, Ia and IIa. At potentials less positive than the peak potential (Ep) for peak Ia, 1 is oxidized to a radical intermediate which dimerizes

  已在热解石墨电极（PGE）的中性水溶液中研究了哺乳动物中央生物碱1-甲基-6-羟基-1,2,3,4-四氢-β-咔啉（1）的电化学氧化。1的伏安图显示两个紧密间隔的氧化峰Ia和IIa。在电位小于峰值Ia的峰值电位（Ep）的情况下，1被氧化成自由基中间体，该中间体二聚化得到5,5'-bi（1-methyl-6-hydroxy-1,2,3， 4-四氢-β-咔啉）（5和6）。在比峰1a的电位更强的Ep上，假定的自由基中间体被进一步电氧化为以C（5）为中心的碳正离子，在离子-底物反应中与1反应生成5和6或与水反应生成最终的1-甲基1,2,3,4-四氢-β-咔啉-5,6-二酮（12）。二聚体5和6在PGE处产生两个可逆的氧化峰，第二个对应于在1伏安图中观察到的峰IIa。由于5和6是易于氧化的化合物，因此它们仅在受控电势电氧化的初始阶段被观察到1.酪氨酸酶/ O2，人铜蓝蛋白/ O2和过氧化物酶/ H2