On-DNA Synthesis of Privileged Dihydropteridinones via Diboron-Mediated Cyclizations

DNA-encoded chemical library (DECL) technology has emerged as a pivotal platform for high-throughput screening in drug discovery. Expanding the chemical space of DECLs requires the development of novel, robust, and DNA-compatible transformations, with atom-economical cyclizations being particularly attractive for generating drug-like scaffolds. The 7,8-dihydropteridinone core represents a pharmacologically important heterocycle whose incorporation into DECLs has been hampered by harsh synthetic conditions. Herein, we report two distinct diboron-mediated catalytic strategies that enable efficient on-DNA synthesis of diverse 7,8-dihydro-6(5H)-pteridinone derivatives. Both methods proceed under mild, aqueous-compatible conditions and afford high conversions, providing a powerful solution for accessing this privileged scaffold.