Visible‐light photoredox‐catalyzed desulfurization of thiol‐ and disulfide‐containing amino acids and small peptides

Abstract

A scalable protocol for the desulfurization of cysteine by using visible light, the photocatalyst Ir(dF(CF )ppy) (dtb-bpy)PF and triethylphosphite under biphasic reaction conditions has been developed. The loading of the catalyst can be as low as 0.01 mol%, which can be efficiently removed during the workup (≤0.3 ppm), giving rise to the corresponding desulfurized product in high yields. This method has been applied also to cystine, penicillamine, and reduced and oxidized glutathione. The desulfurization has been found to be pH sensitive, with an optimal pH value of 6.5 and 7.0 for the cysteine derivatives and glutathione, respectively. In addition, during the desulfurization of a decapeptide containing cysteine and methionine, concurrent oxidation of the two sulfur-containing residues to disulfide and sulfoxide has been observed. Therefore, whereas the presented protocol allows a straightforward visible light-mediated desulfurization of simple thiols by using very low catalyst loading and a cost-effective trialkylphosphite as thiyl radical trapping agent, its application to complex substrates needs to be carefully validated. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Visible-Light-Triggered C–C and C–N Bond Formation by C–S Bond Cleavage of Benzylic Thioethers

“…Even if this approach has been extensively studied to synthesize sulfoxides, 5 it remains a surprisingly underexplored strategy concerning the fragmentation of thioethers. 6 Only in 2013, Bowers and co-workers made a proof of this concept with the first example of photocatalyzed glycosylation of thioglycosides induced by selective oxidation of a thioether. 7 More recently, our group reported an efficient synthesis of αsubstituted amides by photoredox-catalyzed C−S bond cleavages of α-amidosulfides.…”

“…In the meantime, the selective oxidation of thioethers is efficiently ensured by photoredox catalysis since it does not proceed by coordination of the sulfur atom to the catalyst. Even if this approach has been extensively studied to synthesize sulfoxides, it remains a surprisingly underexplored strategy concerning the fragmentation of thioethers . Only in 2013, Bowers and co-workers made a proof of this concept with the first example of photocatalyzed glycosylation of thioglycosides induced by selective oxidation of a thioether .…”

Advances in Native Chemical Ligation–Desulfurization: A Powerful Strategy for Peptide and Protein Synthesis

“…a) Desulfurization catalyzed by [Ru(bpy) 3 ] 2+ . b) Desulfurization catalyzed by [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6 . c) Metal‐free desulfurization of polymer by utilizing visible light …”

“…Followed by this, another visible‐light‐mediated method using [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6 was reported by Reiser and co‐workers in 2017. In this study, only simple Cys derivatives and small thiol‐containing peptides were investigated and the desulfurized products were obtained in acceptable yields.…”

“…[18] b) Desulfurization catalyzed by [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6 . [19] c) Metal-free desulfurization of polymer by utilizing visible light. [20] 12 hours, whereas the TCEP/LiBEt 3 Hs ystem worked well at room temperature.…”