DNA-Compatible Synthesis of Pyrrolidine-Fused Scaffolds via a One-Pot Three-Component Cycloaddition Strategy
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.
Authors
- Peng Zhao (ORCID: https://orcid.org/0000-0003-4377-1035)
- Yuting Gao (ORCID: https://orcid.org/0000-0003-4552-3633)
- Yangfeng Li (ORCID: https://orcid.org/0000-0002-4780-6154)
- Gong Zhang (ORCID: https://orcid.org/0000-0002-6992-176X)
- Yijun Li (ORCID: https://orcid.org/0000-0002-6788-0730)
- Xianfeng Li (ORCID: https://orcid.org/0000-0002-0000-8809)
- Yizhou Li (ORCID: https://orcid.org/0000-0003-1650-3780)
- Xiaohong Fan (ORCID: https://orcid.org/0000-0001-8460-8678)
- Shoucai Ma
Institutions
- Target (United States) (US)
- Chongqing University (CN)
- China Academy of Engineering Physics (CN)
- Institute of Nuclear Physics (UZ)
- Sichuan Mianyang 404 Hospital (CN)
- Chongqing Three Gorges University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1021/acs.orglett.5c02757
- Citations
- 4
- Primary Topic
- Chemical Synthesis and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Chongqing