大学化学 >> 2026, Vol. 41 >> Issue (5): 210-221.doi: 10.12461/PKU.DXHX202510066

所属专题： 第5届全国大学生化学实验创新设计大赛

专题 上一篇    

抗癌药物艾乐替尼的生物电子等排体的合成

刘伟哲, 时铭慧, 朱瑞祺, 潘斌, 黄国富   

  1. 潍坊科技学院化工与环境学院, 山东 寿光 262700
  • 收稿日期:2025-10-16 录用日期:2025-12-26 发布日期:2026-05-21
  • 通讯作者: 潘斌, 黄国富 E-mail:bpan@wfust.edu.cn;hgflh007@163.com Bin Pan, Guofu Huang
  • 基金资助:
    潍坊市科技发展计划2025GX040

Synthesis of a bioisostere of the anticancer drug Alectinib

Weizhe Liu, Minghui Shi, Ruiqi Zhu, Bin Pan, Guofu Huang   

  1. School of Chemical Engineering and Environment, Weifang University of Science and Technology, Shouguang 262700, Shandong Province, China
  • Received:2025-10-16 Accepted:2025-12-26 Published:2026-05-21
  • Contact: Bin Pan, Guofu Huang E-mail:bpan@wfust.edu.cn;hgflh007@163.com

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摘要： 本研究以抗癌一线药物艾乐替尼为研究对象，设计并完成了呋喃基中间体的合成实验。以廉价易得的原料通过3步连续反应获得目标产物。该实验优化了中间体分离和纯化步骤，将总时长控制在8 h内，总收率稳定在75%-80%，适合本科实验教学开设。通过对产物的核磁共振氢谱(1H NMR)和质谱(MS)的解析提升了学生的分析能力，使学生熟悉有机化学研究的一般流程。本实验旨在将课堂思政元素(原创药物对国家安全的重大意义)与有机化学基础(缩合反应、取代反应)、药物化学基础(生物电子等排)、有机波谱学(NMR、MS)等多学科知识相结合，培养学生提出问题、分析问题、解决问题的能力。将前沿药物发展引入教学中，培养多学科交叉的科学思维，将学无止境深植于学习理念中。锻炼学生知行合一的能力，为将来从事科学研究积累经验、培养技能、增强信心。本实验充分尊重学生学习能力的个体差异，通过设定阶梯化难度目标，满足学生的差异化学习诉求，在有机化学和药物化学理论教学和实验创新做了有益探索。

关键词: 生物电子等排, 艾乐替尼, 芳香亲核取代, 缩合反应, 核磁共振氢谱

Abstract: This study focused on the first-line anticancer drug Alectinib, designing and synthesizing a furan-based intermediate through a three-step reaction sequence using cost-effective and readily available starting materials. The optimized protocol minimized intermediate isolation and purification steps, achieving completion within 8 hours with a consistent yield of 75%–80%, making it suitable for undergraduate laboratory instruction. Structural characterization by proton nuclear magnetic resonance spectrum (1H NMR) and mass spectrometry (MS) enhanced students’ analytical skills while familiarizing them with standard organic synthesis workflows. The experiment successfully integrated ideological education (highlighting the national security significance of original drug development) with multidisciplinary knowledge spanning organic chemistry (condensation and substitution reactions), medicinal chemistry (bioisosterism), and spectroscopic analysis (NMR and MS). Designed to cultivate problem-solving abilities, this pedagogical approach introduces cutting-edge pharmaceutical research while fostering interdisciplinary thinking and lifelong learning principles. Through tiered learning objectives, the experiment accommodates diverse student capabilities, serving as an innovative model for integrating theoretical and practical education in organic and medicinal chemistry.

Key words: Principle of bioisosterism, Alectinib, Nucleophilic aromatic substitution, Condensation reaction, Proton nuclear magnetic resonance spectrum