1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole | 67199-08-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole
• 英文别名: 1-acetyl-5-methoxy-2,3,8,8a-tetrahydro-1H-pyrrolo[2,3-b]indol-3a-ol；Cyclic 3-Hydroxy Melatonin；1-(8b-hydroxy-7-methoxy-1,2,3a,4-tetrahydropyrrolo[2,3-b]indol-3-yl)ethanone
• CAS: 67199-08-0
• 化学式: C₁₃H₁₆N₂O₃
• 分子量: 248.282
• InChiKey: VADOSKJWFKUPQF-UHFFFAOYSA-N

物化性质

• 沸点：
  498.2±45.0 °C(Predicted)
• 密度：
  1.328±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  褪黑素 在 peroxynitrite 、 碳酸氢钠 、 sodium chloride 作用下， 以 盐酸 、 phosphate buffer 为溶剂， 反应 0.28h， 生成 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole 、 1-(3alpha-羟基-7-甲氧基-1,2,4,8B-四氢吡咯并[2,3-b]吲哚-3-基)乙酮
  参考文献：
  名称：

  Reaction of Peroxynitrite with Melatonin:  A Mechanistic Study

  摘要：

  The pH profile of the peroxynitrite/melatonin reaction suggests that both peroxynitrous acid (ONOOH) and its anion (ONOO-) are reactive toward melatonin, but at physiological pH most of the reaction with melatonin involves ONOOH and the activated form of peroxynitrous acid (ONOOH*). The formation of hydroxylated products (mainly 6-hydroxymelatonin) suggests that melatonin also reacts with ONOOH*. The overall peroxynitrite/melatonin reaction is first-order in melatonin and first-order in peroxynitrite, but the hydroxylation of melatonin is presumed to be zero-order in melatonin. Melatonin is metabolized in the liver, mainly to 6-hydroxymelatonin, so we do not think this metabolite is a useful biomarker for melatonin's antioxidant activity; however, 6-hydroxymelatonin is a better chain-breaking antioxidant than melatonin and may contribute to the beneficial effects of melatonin in vivo. As is now well-known, CO2 modulates the reactions of peroxynitrite. The reaction of peroxynitrite with melatonin in the absence of added bicarbonate produces mainly 6-hydroxymelatonin and 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-8a-hydroxypyrrolo[2,3-b]indole, with some isomeric 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole. In the presence of added bicarbonate, product yields decrease and 6-hydroxymelatonin is not formed. These facts suggest that melatonin scavenges reactive species (such as CO3.- and (NO2)-N-.) that are produced from the peroxynitrite/CO2 reaction. The spectrum of the melatoninyl radical cation is observed both in the absence and in the presence of added bicarbonate, suggesting that the melatoninyl radical cation is the initial product and the hydroxypyrrolo[2,3-b]indole products are derived from it. Unlike tyrosine, where both nitrated and hydroxylated products can be isolated, nitromelatonin is not found in the final products from the melatonin/peroxynitrite reaction in either the absence or presence of added bicarbonate. However, we suggest that 2-hydroxy-3-nitro- and/or 2-hydroxy-3-peroxynitro-2,3-dihydromelatonin are formed as intermediates and subsequently decompose to give 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-8a-hydroxypyrrolo-[2,3-b]indole. [2,3-b]indole. Since peroxynitrite/CO2 governs the reactions of peroxynitrite in vivo, we suggest that the hydroxypyrrolo[2,3-b]indole products are the main products from the oxidation of melatonin by peroxynitrite-derived species in vivo, and that these products may serve as indexes for melatonin's antioxidant activity.

  DOI：

  10.1021/tx980243t

文献信息

• Reaction of Peroxynitrite with Melatonin:  A Mechanistic Study
  作者：Houwen Zhang、Giuseppe L. Squadrito、Rao Uppu、William A. Pryor

  DOI：10.1021/tx980243t

  日期：1999.6.1

  The pH profile of the peroxynitrite/melatonin reaction suggests that both peroxynitrous acid (ONOOH) and its anion (ONOO-) are reactive toward melatonin, but at physiological pH most of the reaction with melatonin involves ONOOH and the activated form of peroxynitrous acid (ONOOH*). The formation of hydroxylated products (mainly 6-hydroxymelatonin) suggests that melatonin also reacts with ONOOH*. The overall peroxynitrite/melatonin reaction is first-order in melatonin and first-order in peroxynitrite, but the hydroxylation of melatonin is presumed to be zero-order in melatonin. Melatonin is metabolized in the liver, mainly to 6-hydroxymelatonin, so we do not think this metabolite is a useful biomarker for melatonin's antioxidant activity; however, 6-hydroxymelatonin is a better chain-breaking antioxidant than melatonin and may contribute to the beneficial effects of melatonin in vivo. As is now well-known, CO2 modulates the reactions of peroxynitrite. The reaction of peroxynitrite with melatonin in the absence of added bicarbonate produces mainly 6-hydroxymelatonin and 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-8a-hydroxypyrrolo[2,3-b]indole, with some isomeric 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole. In the presence of added bicarbonate, product yields decrease and 6-hydroxymelatonin is not formed. These facts suggest that melatonin scavenges reactive species (such as CO3.- and (NO2)-N-.) that are produced from the peroxynitrite/CO2 reaction. The spectrum of the melatoninyl radical cation is observed both in the absence and in the presence of added bicarbonate, suggesting that the melatoninyl radical cation is the initial product and the hydroxypyrrolo[2,3-b]indole products are derived from it. Unlike tyrosine, where both nitrated and hydroxylated products can be isolated, nitromelatonin is not found in the final products from the melatonin/peroxynitrite reaction in either the absence or presence of added bicarbonate. However, we suggest that 2-hydroxy-3-nitro- and/or 2-hydroxy-3-peroxynitro-2,3-dihydromelatonin are formed as intermediates and subsequently decompose to give 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-8a-hydroxypyrrolo-[2,3-b]indole. [2,3-b]indole. Since peroxynitrite/CO2 governs the reactions of peroxynitrite in vivo, we suggest that the hydroxypyrrolo[2,3-b]indole products are the main products from the oxidation of melatonin by peroxynitrite-derived species in vivo, and that these products may serve as indexes for melatonin's antioxidant activity.