Backbone amide linker strategy for the synthesis of 1,4-triazole-containing cyclic tetra- and pentapeptides

A backbone amide linker strategy was chosen for the solid-phase synthesis of triazole-containing Cyclic tetra- and pentapeptides. An alkyne-substituted linker derived from 4-hydroxy-2-methoxybenzaldehyde was elongated by using standard Fmoc-based solid phase chemistry and terminated by coupling of an azido acid. In solution, the peptides were cyclized by a Cu-1-catalyzed azide-alkyne cycloaddition reaction. The solid-supported synthesized linear peptides had to be cleaved prior to cyclization. As an example of cyclic tetrapeptides, a triazole analog of cyclo-[Pro-Val-Pro-Tyr] (2) was prepared by the solid-phase/solution-phase method. For the cyclic pentapeptides, segetalin B (3) was chosen as a model compound to show the applicability of this method. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).