This randomized trial demonstrates how α-aminoamides are synthesized under DNA-compatible conditions, suggesting new possibilities in library development.
We report the first direct solution-phase on-DNA Ugi three-component reaction for the selective synthesis of α-aminoamides under mild, DNA-compatible conditions. The optimized reaction provides selective access to the desired products by minimizing competing reaction pathways. The method exhibits broad substrate scope for DNA-conjugated anilines and is applicable to representative DNA-conjugated aldehydes and isocyanides. This work expands the repertoire of DNA-compatible multicomponent reactions and provides access to privileged α-aminoamide scaffolds for DNA-encoded libraries.
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Lee et al. (2026) studied this question.
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