绿色合成理念融入药物化学实验教学——以伊马替尼的合成和鉴定为例

Integrating Green Synthesis Concept into Medicinal Chemistry Experimental Teaching:Imatinib Synthesis and Identification as an Example

为将绿色合成理念融入药物化学实验教学中,笔者将科研工作中取得的研究成果融入实验教学,设计了伊马替尼的合成和鉴定的综合实验案例。优化化学过程是绿色合成化学的核心任务之一,在设计的综合实验案例中,将伊马替尼的文献合成方法后2步骤的合成方法--化合物3与对氯甲基苯甲酰氯反应得到苯甲酰胺化合物4,然后由4与N-甲基哌嗪反应得到伊马替尼游离碱5,优化为将步骤4和5两步反应改为在“一锅”反应瓶中通过In-situ原位连续串联反应得到。实验综合了多种基本单元操作和多种测试分析方法。通过本实验,学生不仅巩固了多个基本合成技能,还加深了药物合成原理的理解,充分感受到了药物绿色合成的乐趣与挑战性。

To integrate concept of green synthesis into Medicinal Chemistry experiment teaching,the author has incorporated research achievements obtained during scientific research work into teaching,and designed a comprehensive experiment case for the synthesis and identification of Imatinib.Optimizing chemical processes is one of the core tasks in green synthetic chemistry,in the designed case,the synthesis method of Imatinib from the literature was optimized by modifying the last key two steps-compound 3 reacting with p-chloromethylbenzoyl chloride to form benzamide compound 4,followed by the reaction between 4 and N-methylpiperazine to form Imatinib free base 5-into a single-pot reaction through in-situ continuous tandem reaction.The case combines multiple basic unit operations and analysis methods.Through this experiment,students have not only consolidated multiple basic synthetic skills,but also deepened their understanding of drug synthesis principles,fully enjoyed the pleasure and challenges from green chemical synthesis.