Switchable Synthesis of 7‐ and 14‐Membered Cyclic Peptides Containing N‐Methyl‐ and β‐Amino Acids Utilizing Microflow Technology

Abstract

AbstractSmaller 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 β‐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 (≤16‐membered) cyclic N‐methylated peptides via dimerization‐cyclization strategy.