Tandem Nitro Reduction and Amide Condensation for the On-DNA Synthesis of Natural Product-Inspired Skeletons

To facilitate the efficient incorporation of natural product elements into DNA-encoded libraries, a robust, metal-free, DNA-compatible protocol for nitro reduction and in situ amide condensation has been developed. This methodology utilizes DNA-conjugated (hetero)aromatic nitro electrophiles and simple amino acids as starting materials, enabling the efficient synthesis of structurally diverse DNA-conjugated skeletons that represent core motifs commonly found in bioactive molecules or natural products.