大学化学 >> 2022, Vol. 37 >> Issue (6): 2201038.doi: 10.3866/PKU.DXHX202201038

化学实验 上一篇    下一篇

6, 7-二甲氧基-1, 2, 3, 4-四氢异喹啉-3-羧酸甲酯的制备——介绍一个大学药物化学综合实验

郭举(), 高艺, 胡诗敏, 樊可, 龙思会   

  • 收稿日期:2022-01-19 录用日期:2022-04-15 发布日期:2022-04-25
  • 通讯作者: 郭举 E-mail:guoju1984@163.com
  • 作者简介:郭举, Email: guoju1984@163.com
  • 基金资助:
    武汉工程大学校长基金(XZJJ2021095);武汉工程大学科学研究基金项目(K2021009)

Preparation of Methyl 6, 7-Dimethoxy-1, 2, 3, 4-Tetrahydroisoquinoline-3-Carboxylate: A Comprehensive College Medicinal Chemistry Experiment

Ju Guo(), Yi Gao, Shimin Hu, Ke Fan, Sihui Long   

  • Received:2022-01-19 Accepted:2022-04-15 Published:2022-04-25
  • Contact: Ju Guo E-mail:guoju1984@163.com

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摘要：

介绍了我校制药工程专业和药物制剂专业开展的一个综合药物化学实验，该实验以合成PARP1抑制剂的关键中间体6, 7-二甲氧基-1, 2, 3, 4-四氢异喹啉-3-羧酸甲酯为目标分子，该化合物是作者课题组目前正在研究的PARP1抑制剂的关键中间体，其合成方法是以L-3, 4-二甲氧基苯丙氨酸为原料，甲醇为溶剂，二氯亚砜为脱水剂，室温条件下合成L-3, 4-二甲氧基苯丙氨酸甲酯，再以多聚甲醛为原料，二氯甲烷为溶剂，三氟乙酸为催化剂，经Pictet-Spengler反应合成6, 7-二甲氧基-1, 2, 3, 4-四氢异喹啉-3-羧酸甲酯，目标化合物的结构使用1H NMR、MS等分析方法进行表征。本实验有益于激发学生独立思考能力和研究意识，训练学生的综合实验操作技能和有机化合物的结构鉴定能力，培养学生掌握药物合成科学研究的基本思路和基本方法。

关键词: L-3, 4-二甲氧基苯丙氨酸, 多聚甲醛, Pictet-Spengler反应, 6,7-二甲氧基-1, 2, 3, 4-四氢异喹啉-3-羧酸甲酯

Abstract:

A comprehensive medicinal chemistry experiment performed by students in our school majoring in pharmaceutical engineering and pharmaceutics is introduced. In this experiment, L-3, 4-dimethoxyphenylalanine methyl ester was synthesized from L-3, 4-dimethoxyphenylalanine and methanol by using dichlorosulfoxide as the dehydrating agent at room temperature. Then, methyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylate was prepared from L-3, 4-dimethoxyphenylalanine methyl ester and paraformaldehyde via the Pictet-Spengler reaction using dichloromethane as the solvent and trifluoroacetic acid as a catalyst. The structure was characterized using 1H NMR spectroscopy and MS. This experiment is beneficial to students for the following reasons: stimulating independent thinking and cultivating research-mindedness, comprehensively training both technical lab skills and structural identification of organic compounds, and mastering the principles and methods of scientific research on drug synthesis.

Key words: L-3, 4-Dimethoxyphenylalanine, Paraformaldehyde, Paraformaldehyde, Pictet-Spengler reaction, Methyl 6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylate