DNA-Compatible Synthesis of β-Ketoamides as Intermediates for On-DNA Chemical Diversification

The β-ketoamide motif represents both a privileged scaffold and a versatile synthetic intermediate in medicinal chemistry. Herein, we developed a DNA-compatible method for the efficient conversion of various DNA-conjugated amines into β-ketoamides. The resulting β-ketoamides facilitate rapid diversification into a panel of structurally diverse molecular scaffolds. Importantly, the synthetic route and subsequent derivatization steps were validated to be fully compatible with DNA encoding, offering a reliable and versatile platform for DNA-encoded library synthesis.