Orthogonal Electrochemical Amine Deprotection: Toward Sustainable Strategies for Peptide Synthesis

Deprotection steps employed in peptide synthesis often require harsh conditions and excess reagents, limiting substrate compatibility and sustainability. Electrochemically cleavable protecting groups (e-PGs) offer an attractive alternative. Here, we report the use of 1,3-dithiane-based e-PGs for orthogonal protection of lysine ε-amines in peptide synthesis. Under constant potential electrolysis, deprotection proceeds selectively and orthogonally to other common amino acid protecting groups (Alloc, Boc, Dde, Fmoc, Trt, Pbf, tBu), highlighting potential applications in sustainable peptide synthesis.