Peptide Synthesis in Aqueous Solution. I. Application of p-Dialkylsulfoniophenols as a Water-Soluble Coupling Reagent

Abstract (p-Hydroxyphenyl)dimethylsulfonium methyl sulfate(HODMSP·MeSO4−) was found to be an excellent coupling reagent having a water-soluble property and a high reactivity; it worked as satisfactory as usual active esters in regard to the reactivity, product purity, and racemization. The marked advantage of the HODMSP·MeSO4− active ester method was the fact that bifunctional residues such as Arg, Lys, Cys, and Tyr could be selectively acylated when the pH of the reaction mixture was controlled. The molluscan neuropeptide FMRFamide(Phe–Met–Arg–Phe–NH2) was synthesized by this new active ester method for an evaluation of this method to further applications involving peptide syntheses.