Development of Solid-Phase DNA-Encoded Library Synthesis of Oxazoles
Solution-phase chemistry has been extremely useful for DNA-Encoded Library (DEL) synthesis. However, not all chemical reactions are compatible with solution-phase methods. To broaden our arsenal of on-DNA reactions and diversify our library collections, we explored solid-phase DEL synthesis in the context of a highly desirable oxazole formation. This work addresses key operational challenges in solid-phase DEL chemistry and demonstrates a modular, scalable workflow for oxazole library construction. Our approach enables further exploration of oxazole-based chemical space and supports solid-phase synthesis as a viable strategy for future DEL development, especially for cases where solution-phase chemistry is not amenable.