A novel method for the synthesis of macrocyclic peptides using arylsulfonyloxyacetic acids as N-terminus functional groups

We have successfully introduced arylsulfonyloxyacetic acids with long alkyl chains as lipophilic tags to the N-terminus of peptides in the final step of solid phase peptide synthesis in order to purify tagged peptides. Also, the tags allow the linear peptides to be purified by solidification after liquid–liquid extraction. Moreover, macrocyclic peptide 1 after cyclization reaction was pre-purified easily by separating the arylsulfonate produced from tags. In this report, we described the application of this methodology to the synthesis of macrocyclic peptides such as carbetocin analogues with thioether-, amino-, ether- and ester-linkage could be derived from tagged peptides.