Micelle-Mediated Sonogashira Coupling for DNA-Encoded Library Synthesis

DNA-Encoded Libraries (DELs) are becoming widely established as a hit identification strategy for drug discovery campaigns. Their successful application relies on the availability and efficiency of the reactions that can be carried out on DNA. These reactions should proceed with high conversion to the desired product and have a broad substrate scope to synthesise chemically diverse and drug-like DELs. The Sonogashira coupling provides a unique means of coupling an sp-hybridized carbon centre to an aryl halide and methods to achieve this reaction on DNA are highly desirable. We report the application of our micellar technology for on-DNA chemistry to the Sonogashira reaction. This method gives highly efficient conversions for the coupling of (hetero)aromatic and aliphatic alkynes to (hetero)aryl iodides and bromides allowing the preparation of highly diverse DELs.

Automated summary

DNA-Encoded Libraries (DELs) are widely used as a hit identification strategy for drug discovery campaigns. The success of DELs relies on efficient reactions that can be carried out on DNA. The Sonogashira coupling is an important reaction for on-DNA chemistry, allowing the efficient coupling of alkynes to aryl halides. Our micellar technology provides highly efficient conversions for the Sonogashira reaction, enabling the synthesis of diverse DELs.