Coupling-Reagent-Free Synthesis of Dipeptides and Tripeptides Using Amino Acid Ionic Liquids

A general method for the synthesis of dipeptides has been developed, which does not require any coupling reagents. This method is based on the reaction of readily available HCl salts of amino acid methyl esters with tetrabutylphosphonium amino acid ionic liquids. The isolation procedure of stepwise treatment with AcOH is easy to carry out. The method was extended to the synthesis of tripeptide, tyrosyl‐glycyl‐glycine, present in IMREG‐1, also. Free at last! A novel coupling‐reagent‐free method for the synthesis of dipeptides by reaction of readily available HCl salts of amino acid methyl esters with phosphonium‐based amino acid ionic liquids (AAIL) was developed. A variety of dipeptides can be prepared in good to high yields by this procedure and their isolation is accomplished by simple treatment with AcOH.