Reaction development for DNA-encoded library technology: From evolution to revolution?

DNA-encoded libraries of organic, synthesized molecules are an emerging technology for target-based compound screening. The design of first generation encoded libraries placed emphasis on ever increasing compound numbers that were synthesized from large sets of starting materials with a few well-established synthesis methods. In the last two years there has literally been an explosion of published research activities that have expanded the toolbox of reactions for designing DNA-encoded libraries. In this digest, we highlight latest developments that include modern photoredox chemistries as well as strategies to perform encoded compound synthesis in organic solvents or exploit nano-heterogeneous systems. The new chemistry developments carry the potential to revolutionize the technology as they enable access to unprecedented molecular diversity.