FeCl3-Mediated Boc Deprotection: Mild Facile Boc-Chemistry in Solution and on Resin

A mild, practical, and straight forward method for Boc deprotection and its use in peptide synthesis both in solution and on solid support is presented. Boc protecting group is removed from the N-terminal amino acid of the amino acid and the peptide using environment-friendly cost-effective Lewis acid, FeCl3. The deprotected amino group undergoes C-N bond formation with the next Boc-protected amino acid in the presence of a suitable coupling reagent and base. A library of di- to tetrapeptides is synthesized with moderate to good yield from standard and nonstandard Boc-protected amino acids in solution. Most importantly, this protocol can be used for the solid-phase peptide synthesis (SPPS) using Boc-protected amino acids on the acid-sensitive Rink amide resin, which is usually used for Fmoc chemistry. This protocol thus allows practicing Boc chemistry in a greener manner, and on-demand switching from Fmoc to Boc chemistry and vice-versa while synthesizing one oligopeptide on the same resin. The inherent orthogonality of Fmoc and Boc chemistry allows facile synthesis of branched and cyclized peptides on the resin as well.