DNA-encoded chemical libraries have emerged as a cost-effective alternative to high-throughput screening (HTS) for hit identification in drug discovery. A key factor for productive DNA-encoded libraries is the chemical diversity of the small molecule moieties that are attached to the encoding DNA oligomers. However, library structural diversity is often limited by the available toolbox of DNA-compatible, aqueous chemical reactions. To further expand available structural diversity, we have developed several new conditions for DNA-chemical conjugate synthesis, including two efficient systems for the reduction of nitro groups, and protocols for the multistep synthesis of benzimidazoles and oxadiazoles. The developed nitro reduction conditions provided good to excellent yields of amines in presence of a variety of functional groups, and was utilized in the synthesis of several benzimidazoles and other types of DNA-encoded libraries. The multistep synthesis of oxadiazoles was conducted on DNA-conjugated nitrile substrates and also applied in the synthesis of a DNA-encoded chemical library.

DNA-compatible nitro reduction and multistep synthesis of benzimidazoles and oxadiazoles

2019 Fall National Meeting

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