Katarzyna Joanna Malawska, Masashi Suzuki, Junko Sasaki, Masaki Koshimizu, Kazuma Kaitoh, Hiroyuki Miyachi, Motomu Kanai

Organic Letters

DOI: 10.1021/acs.orglett.6c02201

Abstract

DNA-encoded libraries (DELs) enable the rapid interrogation of vast chemical spaces for ligand discovery; however, their structural diversity remains constrained by the availability of DNA-compatible chemical transformations. Incorporating pharmacologically active scaffolds that require oxidative or heterocycle-forming reactions is challenging because of the sensitivity of DNA. Here, we demonstrate that a tryptophan-selective bioconjugation based on the keto-ABNOH/TEMPO⁺ system is fully compatible with DEL synthesis, enabling the construction of a biologically privileged hydroxypyrroloindoline carboxylic acid (HPIC) scaffold.