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Evolution of the Process to an Advanced GPR40 Agonist (1)

有机合成与工艺文献分享 2025-04-15 07:35
文章摘要
本文主要探讨了高级GPR40激动剂(1)的合成工艺优化。背景方面，传统药用化学路线通常采用预先引入手性中心的芳基碘化物(2)与取代脯氨醇(3)偶联的方法。研究目的旨在开发克级规模的合成新路线，提出通过α,β-不饱和酯23的分子内迈克尔加成形成吡咯烷环的创新方法。结论表明，该环化反应在过量碱存在下可在室温以下高效进行，能以7:1的比例优势获得所需的反式(1,2-反式)立体构型产物35，同时研究还发现可通过与4-氟硝基苯(25)的SNAr反应高产率地引入手性哌啶醇片段。
Evolution of the Process to an Advanced GPR40 Agonist (1)
查看文献： Evolution of the Synthetic Process to an Advanced GPR40 Agonist
查看期刊：Organic Process Research & Development
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