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A bridging strategy demonstrates effective on-DNA Dithiocarbamate synthesis in medicinal chemistry, implying new therapeutic avenues.
Dithiocarbamates (DTCs) are privileged scaffolds in medicinal chemistry, yet inaccessible via DNA‐encoded libraries (DELs) due to a lack of robust on‐DNA synthesis. We developed a general procedure for on‐DNA DTC formation using a carbon disulfide (CS 2 ) bridging strategy. This method efficiently links diverse aliphatic secondary amines and alkyl halides under mild conditions with high conversions and excellent DNA compatibility. The utility of this method was demonstrated by constructing a prototype DEL, thereby bridging a critical gap in chemical space and facilitating the rapid discovery of DTC‐based therapeutics.
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Wang et al. (2026) studied this question.
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