Reagent-Based Scaffold Diversity for DNA-Encoded Library Design: Solid Phase Synthesis of DNA-Tagged sp3‑Rich Heterocycles by SnAP Chemistry

Reactions that require strictly dry conditions are challenging to translate to a DNA-encoded library format. Controlled pore glass solid support-connected DNA oligonucleotide–aldehyde conjugates could be condensed with SnAP reagents and cyclized to various sp3-rich heterocycles. The Boc-group of products provided a handle for product purification, and its facile removal under acidic conditions was tolerated by a chemically stabilized barcode. The reaction provides reagent-based scaffold diversity with functionalities for further library synthesis.