Solid-Phase Synthesis Utilizing Azido-α-Amino Acids: Reduction of Azido-Protected Proline

Abstract

During an evaluation of azido-α-amino acids and their utility in solid-phase peptide chemistry, the octapeptide angiotensin II and a tripeptide thyrotropin-releasing hormone (TRH) analog have been prepared using Meldal’s procedure [1]. A necessary novel step was the reduction of the azido moiety of L-proline, a secondary amine constrained by a ring, to the corresponding free amine for coupling and peptide elongation. In this step a solution of tin(II)chloride (SnCl₂), thiophenol (PhSH) and triethylamine (TEA) [2] in dimethylformamide (DMF) was added at ambient temperature to the azido-L-proline-peptide-resin to afford the desired free amino group (Figure 1) and make the use of azido- α-amino acids more general for solid-phase peptide synthesis.