sp 3 ‐Rich Heterocycle Synthesis on DNA: Application to DNA‐Encoded Library Production

作者：Felix Gruber, Anthony W. McDonagh, Victoria Rose, James H. Hunter, Laura Guasch, Rainer E. Martin, Stefanie N. Geigle, Robert Britton · 发表于：Angewandte Chemie International Edition · 年份：2024 · DOI：10.1002/anie.202319836 · 被引用次数：10 · 研究领域：Chemical Synthesis and Analysis、RNA and protein synthesis mechanisms、Click Chemistry and Applications

Abstract DNA encoded library (DEL) synthesis represents a convenient means to produce, annotate and store large collections of compounds in a small volume. While DELs are well suited for drug discovery campaigns, the chemistry used in their production must be compatible with the DNA tag, which can limit compound class accessibility. As a result, most DELs are heavily populated with peptidomimetic and sp 2 ‐rich molecules. Herein, we show that sp 3 ‐rich mono‐ and bicyclic heterocycles can be made on DNA from ketochlorohydrin aldol products through a reductive amination and cyclization process. The resulting hydroxypyrrolidines possess structural features that are desirable for DELs and target a distinct region of pharmaceutically relevant chemical space.