Chemical Science Symposium 2022

Biocompatible energy induced late-stage modifications of bioactive compounds and biomolecules Chien-Wei Chiang Soochow University, Chinese Taipei The growing interest in late-stage modifications of bioactive compounds and in peptides and antibody-drug conjugates as drug candidates in current therapeutics has stimulated increased interest in new synthetic strategies. Therefore, introducing new late-stage modification methods has become essential and attractive to researchers. Herein, we report on the mild biomolecule modifications with a single electron transfer (SET) process through the photoredox and electrolysis technologies, achieving the transformation of tryptophan- and tyrosine- containing molecules, respectively.For example, we have achievedan indirect electrochemical strategy and a photoredox method that could incorporate the trifluoromethyl group into tryptophan residue. Besides, wereported an electrochemical strategy to perform the E-bioconjugation of tyrosine residue with phenothiazine derivatives. Importantly, this electrochemical system allowed various polypeptides and proteins labeled with phenothiazine in excellent site- and chemo-selectivity.These protocols would be expected to provide new toolkits for late-stage modification labeling and peptide–drug bioconjugation. References 1. Y. Weng, B. Ding, Y. Liu, C. Song, L.-Y. Chan, and C.-W. Chiang, * “Late-Stage Photoredox C–H Amidation of N-Unprotected Indole Derivatives: Access to N-(Indol-2-yl)amides”, Org. Lett., 2021 , 23, 2710-2714. 2. Y. Weng, C. Song, C.-W. Chiang,* and A. Lei*, “Single electron transfer-based peptide/protein bioconjugations driven by biocompatible energy input”, Commun. Chem., 2020 , 3 , 171. 3. B. Ding, Y. Weng,* Y. Liu, C. Song, L. Yin, J. Yuan, Y. Ren, A. Lei*, and C.-W. Chiang * , “Selective Photoredox Trifluoromethylation of Tryptophancontaining Peptides”, Eur. J. Org. Chem., 2019 , 46 , 7596-7605. 4. C. Song, K. Liu, Z. Wang, B. Ding, S. Wang, Y. Weng,* C.-W. Chiang,* and A. Lei,* “Electrochemical Oxidation Induced Selective Tyrosine Bioconjugation for the Modification of Biomolecules”, Chem. Sci. , 019 , 10 , 7982-7987.

P21

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