Desulfurative Borylation of Small Molecules, Peptides, and Proteins

We introduce a direct conversion of alkyl thiols into boronic acids, facilitated by a water-soluble phosphine, 1,3,5-triaza-7-phospha-adamantane (PTA), in conjunction with tetrahydroxy-diboron (B-2(OH)(4)), acting as both a radical initiator and a boron source. This desulfurative borylation reaction has been successfully applied to various substrates, including cysteine residues in oligopeptides and small proteins, primary alkyl thiols found in pharmaceutical compounds, disulfides, and seleno-cysteine. Optimization of reaction conditions was undertaken to reduce the formation of unwanted reactions, such as the reduction of alanyl or other primary radicals, and to prevent deleterious reactions between the phosphine and N-terminal amine that lead to methylene adducts by utilizing a buffer containing glycine-glycine (GG) dipeptide. The developed method is characterized by its operational simplicity and robustness. Moreover, its compatibility with various functional groups present in peptides and proteins makes it a promising tool for late-stage functionalization, extending its potential application across a broad spectrum of chemical and biological targets.

Automated summary

We introduce a method for the direct conversion of alkyl thiols into boronic acids, which is characterized by its operational simplicity and compatibility with various functional groups present in peptides and proteins, making it a promising tool for late-stage functionalization.