One common approach to the synthesis of MPs and other macrocyclic compounds is to trap an intramolecular imine linkage with an internal or external nucleophile. Depending on the imine trapping strategy, the products can range from simple amines to interesting heterocycles. Based on the work of Aron and others, 10 we hypothesized that an alternative imine trapping strategy would be to expose the To explore the formation of macrocycles using this chemistry, we synthesized the model starting material shown in Figure on 160 µm TentaGel beads with a Rink-amide (RAM) linker. Oxo represents the glyoxamide formed by NaIO4-mediated oxidation of an N-terminal serine. The Mmt protecting group was removed using a 1:3 mixture of hexafluoroisopropanol (HFIP)/DCM, then the beads were exposed to 3 equivalents of pyridine-2-carboxaldehyde in a 1:1 mixture of acetic acid (AcOH) /trifluoroethanol (TFE) for 10 hours at 30 o C. (While the reaction also could be carried out using 5% AcOH/TFE for 10