Issue 2, 2018

Scalable thioarylation of unprotected peptides and biomolecules under Ni/photoredox catalysis

Abstract

Site-specific functionalization of unprotected native peptides and biomolecules remains a useful transformation in synthetic design and chemical biology, yet until recently, advancements in transition metal-catalyzed methods, which have prevailed in organic synthesis, have been relatively ineffective when applied to large and structurally complex biomolecules. Here, the mechanistically distinct, Ni/photoredox-catalyzed arylation of unprotected, native thiols (e.g., cysteine residues) is reported – a process initiated through a visible light-promoted, hydrogen atom transfer (HAT) event under ambient conditions. Sub-stoichiometric loadings of the dual-catalyst system (≤5 mol%) are employed, granting excellent site-specificity, broad substrate scope, and low chemical waste. Reaction scalability (from μg to grams) has been achieved through modest reagent adjustments, and high throughput experimentation (HTE) demonstrates the ease of reaction setup, enabling prompt screening of aryl halide coupling partners and conditions. Scores of thiol substrates and aryl entities were examined and effectively conjugated, suggesting further diverse, practical applications.

Graphical abstract: Scalable thioarylation of unprotected peptides and biomolecules under Ni/photoredox catalysis

Supplementary files

Article information

Article type
Edge Article
Submitted
02 Okt. 2017
Accepted
04 Nov. 2017
First published
13 Nov. 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 336-344

Scalable thioarylation of unprotected peptides and biomolecules under Ni/photoredox catalysis

B. A. Vara, X. Li, S. Berritt, C. R. Walters, E. J. Petersson and G. A. Molander, Chem. Sci., 2018, 9, 336 DOI: 10.1039/C7SC04292B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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