The use of crown ethers in peptide chemistry. Part 2. Syntheses of dipeptide complexes with cyclic polyether 18-crown-6 and their derivatisation with DMSO

Abstract

As part of a study the aim of which is to use crown compounds as non-covalent protecting groups in peptide synthesis, we have explored the reactivity of 18-crown-6-ether-dipeptide complexes with dicyclohexylcarbodi-imide (DCC) in dimethyl sulphoxide (DMSO). At a reactant concentration of ca. 0.02 mol dm^–3 the DCC did not activate the dipeptide, and the N-acylurea derivative slowly formed. At concentrations of ca. 0.2 mol dm^–3 the complexes proved to be unstable and reacted with the solvent to form a DMSO-peptide adduct. The reaction mechanism leading to the latter was elucidated and shown to involve an initial acid-catalysed addition of DMSO to DCC. The presence in solution of nucleophiles gave the peptide ester thus indicating DCC-mediated activation of the peptide carboxylic acid group. The results from this study were used to design the conditions necessary for an effective noncovalent protection of the amino group during peptide synthesis.