Marco Potowski; Verena Kunig; Florian Losch; Andreas Brunschweiger
Med. Chem. Commun., 2019, 10, 1082-1093
https://doi.org/10.1039/C9MD00042A

Abstract

DNA-encoded libraries of chemically synthesized compounds are an important small molecule screening technology. The synthesis of encoded compounds in solution is currently restricted to a few DNA-compatible and water-tolerant reactions. Encoded compound synthesis on short DNA-barcodes covalently connected to solid support benefits from a broad choice of organic solvents. Here we show that this encoded chemistry approach allows for synthesis of DNA-coupled isoquinolones by Yb(III)-mediated Castagnoli-Cushman reaction under anhydrous reaction conditions and for the synthesis of highly substituted pyrrolidines by Ag(I)-mediated 1,3-dipolar azomethine ylide cycloaddition. An encoding scheme for these DNA-barcoded compounds based on a DNA hairpin is demonstrated.