Studies on Peptides. LXXIII. Examination of the Methanesulphonic Acid Procedure for the Synthesis of Peptides containing Methionine

Abstract

Aromatic ethers, such as anisole or phenetole, were cleaved smoothly with methanesulphonic acid (MSA) or trifluoromethanesulphonic acid in the presence of Met to form methionine-S-methyl (or ethyl) sulphonium salt (I). When the protecting group of Z-Met-OH or Boc-Met-OH was cleaved in the MSA-anisole system, (I) was found as a major product, besides a samll amount of S-benzyl or S-tert-butyl derivative. Thus a Met-containing peptide, H-Tyr-Gly-Gly-Gly-Lys-Met-Gly-OH named endorphin, was synthesized after deprotection of Z (OMe)-Tyr-Gly-Gly-Gly-Lys (Z)-Met (O)-Gly-OH by the MSA-anisole procedure followed by reduction of the Met (O) moiety to the parent amino acid residue with dithiothreitol.