Qigui Nie; Tingting Xu; Xianfu Fang; Yanrong Dan; Gong Zhang; Yangfeng Li; Jianbo Li; Yizhou Li
Org. Lett., 2025, 27(1), 498–503
https://doi.org/10.1021/acs.orglett.4c04505

Abstract

We here report an efficient DNA-compatible furan-thiol-amine reaction for macrocyclization and late-stage amine transformation. This reaction, conducted under mild conditions, enables the facile cyclization of DNA-conjugated linear peptides into thiopyrrole-grafted macrocycles regardless of ring size or side-chain modification with good to excellent conversion yields. Additionally, this strategy was employed for the late-stage transformation of terminal amines, serving as critical intermediates in the construction of DNA-encoded peptide libraries. Diverse amines were successfully converted into their corresponding thiopyrrole scaffolds, thereby expanding the structural diversity that can be achieved within DNA-encoded libraries.