On-DNA Synthesis of 2-Hydroxy Dithiocarbamates

We present a modular on-DNA bridging strategy that addresses key reactivity challenges in DNA-encoded library synthesis. By generation of a reactive carbamodithioic acid intermediate from secondary amines, this method enables efficient coupling with epoxides to produce diverse 2-hydroxy dithiocarbamate scaffolds. Gentle and DNA-compatible, it offers a versatile platform for rapid, structurally diverse DEL construction with significant drug discovery potential.