DNA-Compatible Synthesis of Pyrrolidine-Fused Scaffolds via a One-Pot Three-Component Cycloaddition Strategy

作者：Xianfeng Li, Shoucai Ma, Yijun Li, Yijun Li, Yuting Gao, Gong Zhang, Peng Zhao, Yangfeng Li, Yangfeng Li, Xiaohong Fan, Yizhou Li, Yizhou Li · 发表于：Organic Letters · 年份：2025 · DOI：10.1021/acs.orglett.5c02757 · 被引用次数：11 · 研究领域：Chemical Synthesis and Analysis、Click Chemistry and Applications、Synthesis and Catalytic Reactions

Pyrrolidines are privileged scaffolds commonly found in natural products, endowed with distinctive biological activities and significant pharmaceutical relevance. Herein, we describe a robust, DNA-compatible strategy for the efficient synthesis of pyrrolidine-fused scaffolds via a three-component cycloaddition of azomethine ylides. The resulting scaffolds, bearing reactive N-termini, can be further diversified using a range of reagents, thereby enhancing the chemical diversity of drug-like pyrrolidine-fused DNA-encoded library (DEL). Critically, the practical utility of this methodology was demonstrated through its application to on-DNA synthesis of bioactive compounds and the construction of prototype DELs.