Sulphur trioxide/thiol: a novel system for the reduction of methionine sulphoxide

Abstract

A new method for the effective reduction of methionine sulphoxide in protected peptides with sulphur trioxide and thiol has been developed. In practice, a combination of dimethylformamide–sulphur trioxide complex and ethane-1,2-dithiol was found effective, the presence of pyridine in the reaction medium being found necessary for the reduction to proceed. Methionine sulphoxide in two types of protected methionine–enkephalins was efficiently reduced to methionine by this reduction system at 20 °C in an hour. The (p-methylsulphinyl)benzyl protecting group was also reduced to (p-methylthio)benzyl simultaneously with the reduction of methionine sulphoxide. Subsequent deprotection afforded methionine–enkephalin of high purity in each case.