DNA-Compatible Synthesis of Pyrrolidine-Fused Scaffolds via a One-Pot Three-Component Cycloaddition Strategy
Xianfeng LiChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical SciencesShoucai MaChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical SciencesYijun LiChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical SciencesYuting GaoChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical SciencesGong ZhangChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical SciencesPeng ZhaoChina Academy of Engineering PhysicsYangfeng LiChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical SciencesXiaohong FanChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical SciencesYizhou LiChongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences
ABI
Abstract
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.
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