posted on 2024-02-09, 19:18authored byGaonan Wang, Yu Tan, Hanzhi Zou, Xihang Sui, Zhanlong Wang, Alexander L. Satz, Letian Kuai, Wenji Su, Qi Zhang
DNA-encoded chemical library (DECL) technology is a commonly
employed
screening platform in both the pharmaceutical industry and academia.
To expand the chemical space of DECLs, new and robust DNA-compatible
reactions are sought after. In particular, DNA-compatible cyclization
reactions are highly valued, as these reactions tend to be atom economical
and thus may provide lead- and drug-like molecules. Herein, we report
two new methodologies employing DNA-conjugated thiosemicarbazides
as a common precursor, yielding highly substituted 1,3,4-oxadiazoles
and 1,2,4-triazoles. These two novel DNA-compatible reactions feature
a high conversion efficiency and broad substrate scope under mild
conditions that do not observably degrade DNA.