Acceleration of the N^α-Deprotection Rate by the Addition of m-Cresol to Diluted Methanesulfonic Acid and Its Application to the Z(OMe)-Based Solid-Phase Syntheses of Human Pancreastatin-29 and Magainin 1

Abstract

In solid-phase peptide synthesis, the addition of m-cresol to dilluted methanesulfonic acid (MSA) in dichloromethane accelerated the deprotection rate of the acid-labine α-amino protecting group, the p-methoxybenzyloxycarbonyl(Z(OMe)) group. Further, 0.1 M MSA, 20% m-cresol/CH₂Cl₂ was found to be a practically useful N^α-deprotecting reagent system, since the deprotection of the Z(OMe) group occurred selectively within 30 min at room temperature, leaving intact the other side chain protecting groups, such as benzyloxycarbonyl, benzyl ester, S-p-methoxybenzyl and N^G-mesitylene-2-sulfonyl groups. This reagent system was applied to the Z(OMe)-based solid phase syntheses of human pancreastatin-29 and magainin 1.