Backbone Amide Linker Strategy for the Synthesis of 1,4-Triazole-Containing Cyclic Tetra- and Pentapeptides

✍ Scribed by Jasper Springer; Kimberly R. de Cuba; Sandrine Calvet-Vitale; Jan A. J. Geenevasen; Pedro H. H. Hermkens; Henk Hiemstra; Jan H. van Maarseveen

• Book ID: 102173006
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 335 KB
• Volume: 2008
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200800143

✦ Synopsis

Abstract

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^I^‐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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)