On-DNA Synthesis of Multisubstituted Indoles
András Gy Németh1,2, Levente Kollár1,3,2, Krisztina Németh1,4
1Medicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary.
Abstract:
The increasing role of the DNA-encoded library technology in early phase drug discovery represents a significant demand for DNA-compatible synthetic methods for therapeutically relevant heterocycles. Herein, we report the first on-DNA synthesis of multisubstituted indoles via a cascade reaction of Sonogashira coupling and intramolecular ring closure. Further functionalization by Suzuki coupling at the third position exploits a diverse chemical space. The high fidelity of the method also enabled the construction of an indole-based mock library.
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