Switchable Synthesis of 7-and 14-Membered Cyclic Peptides Containing N-Methyl- and & beta;-Amino Acids Utilizing Microflow Technology

Smaller cyclic peptides containing non-proteinogenic amino acids have garnered much attention for use as drugs, but their chemical synthesis is extremely challenging. In this study, a rapid (60.5 min) synthesis of 7- and 14-membered cyclic peptides containing N-methyl- and & beta;-amino acids was achieved by only switching the concentrations (0.20 M or 0.01 M) of the substrates. The developed approach required neither expensive transition-metals nor expensive coupling agents. As far as we could ascertain, this is the first report of the synthesis of smaller (& LE;16-membered) cyclic N-methylated peptides via dimerization-cyclization strategy.

Automated summary

In this study, smaller cyclic peptides containing non-proteinogenic amino acids were synthesized in a rapid manner (60.5 min) by switching the substrate concentrations. Expensive transition-metals and coupling agents were not required. This is the first report of synthesizing smaller (≤16-membered) cyclic N-methylated peptides via a dimerization-cyclization strategy.