DNA-Compatible Cyclization Reaction to Access 1,3,4-Oxadiazoles and 1,2,4-Triazoles
Gaonan Wang, Yu Tan, Hanzhi Zou, Xihang Sui, Zhanlong Wang, Alexander L. Satz, Letian Kuai, Wenji Su, Qi Zhang
Abstract
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.