(1R,1'S,3S)-3-carboxy-1-(1',2'-dihydroxyethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (1R,1'S,3S)-3-carboxy-1-(1',2'-dihydroxyethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (1R,3S)-1-[(1S)-1,2-dihydroxyethyl]-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 化学式: C₁₂H₁₅NO₆
• 分子量: 269.254
• InChiKey: DCJLAZTZJRNILL-WHGOUJPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  130
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  D-(+)-甘油醛 、 左旋多巴 以 phosphate buffer 为溶剂， 反应 3.0h， 以600 mg的产率得到(1R,1'S,3S)-3-carboxy-1-(1',2'-dihydroxyethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Pictet–Spengler condensation of the antiparkinsonian drug l-DOPA with d-glyceraldehyde. Opposite kinetic effects of Fe3+ and Cu2+ ions and possible implications for the origin of therapeutic side effects

  摘要：

  In 0.05 M phosphate buffer, pH 7.4. and at 37 degreesC, L-DOPA. a widely used antiparkinsonian drug, reacted smoothly with D-glyceraldehyde to afford diastereoisomeric (1R,1 'S,3S)-3-carboxy-1-( 1 ' .2 ' -dihydroxyethyl)-6,7-dihydroxy- 1,1,3,4-tetrahydroisoquinoline (1) and (1S,1 'S,3S)-3-carboxy-1-( 1 ' ,2 ' -dihydroxyethyl)-6,7-dihydroxy- 1,2,3,4-tetrahydroisoquinoline (2) in an approx. 3:2 ratio. The prevalent formation of 1 over 2 reflects stereoselective cyclisation of a transient Schiff base in accord with the Felkin-Anh model. Fe3+ ions, present at relatively high levels in parkinsonian brains, markedly accelerated formation of 1 and 2. whereas Cu2+ decreased the reaction rate, due apparently to different sites of chelate formation between L-DOPA and the metal ions. Both metal ions markedly decreased the stereoselectivity of the reaction. Product 1 exhibited chelating properties toward metal ions comparable or stronger than those of L-DOPA. These results throw new light on the effects of transition metal ions on the Pictet-Spengler reaction and suggest a possible role of tetrahydroisoquinoline products from L-DOPA and carbohydrate metabolites in the severe side effects of the drug. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00309-6

文献信息

• Pictet–Spengler condensation of the antiparkinsonian drug l-DOPA with d-glyceraldehyde. Opposite kinetic effects of Fe3+ and Cu2+ ions and possible implications for the origin of therapeutic side effects
  作者：Paola Manini、Marco d'Ischia、Giuseppe Prota

  DOI：10.1016/s0968-0896(00)00309-6

  日期：2001.4

  In 0.05 M phosphate buffer, pH 7.4. and at 37 degreesC, L-DOPA. a widely used antiparkinsonian drug, reacted smoothly with D-glyceraldehyde to afford diastereoisomeric (1R,1 'S,3S)-3-carboxy-1-( 1 ' .2 ' -dihydroxyethyl)-6,7-dihydroxy- 1,1,3,4-tetrahydroisoquinoline (1) and (1S,1 'S,3S)-3-carboxy-1-( 1 ' ,2 ' -dihydroxyethyl)-6,7-dihydroxy- 1,2,3,4-tetrahydroisoquinoline (2) in an approx. 3:2 ratio. The prevalent formation of 1 over 2 reflects stereoselective cyclisation of a transient Schiff base in accord with the Felkin-Anh model. Fe3+ ions, present at relatively high levels in parkinsonian brains, markedly accelerated formation of 1 and 2. whereas Cu2+ decreased the reaction rate, due apparently to different sites of chelate formation between L-DOPA and the metal ions. Both metal ions markedly decreased the stereoselectivity of the reaction. Product 1 exhibited chelating properties toward metal ions comparable or stronger than those of L-DOPA. These results throw new light on the effects of transition metal ions on the Pictet-Spengler reaction and suggest a possible role of tetrahydroisoquinoline products from L-DOPA and carbohydrate metabolites in the severe side effects of the drug. (C) 2001 Elsevier Science Ltd. All rights reserved.