On-DNA Synthesis of Functionalized 4 H -Pyran Scaffolds for Focused DNA-Encoded Chemical Libraries.

The functionalized 4 H -pyran scaffold has aroused synthetic attention because it is widely found in many interesting pharmacologically relevant compounds. We here disclose its incorporation into DNA-encoded chemical libraries, combining this scaffold with the merits of scaffold architecture in drug design. Under the optimized DNA-compatible conditions, functionalized 4 H -pyrans were efficiently formed with a broad substrate scope. Among the 4 H -pyrans formed, the axial structure features rotational restriction, and the spirocyclic structure provides rigidity and three-dimensionality. These efforts open the door for the construction of DNA-encoded chemical libraries with more consideration for this structural architecture.