Synthesis of the Leu-Trp Component of the Celogentin Family of Cyclic Peptides Through a C-H Activation-Cross-Coupling Strategy

Abstract

A bioinspired approach to the central leucine(C3)-tryptophan(C6) cross-linked moiety present in the celogentin family of cyclic peptide natural products was achieved. The key transformation was enabled through a palladium-catalyzed C-H activationcross-coupling of leucine quinoline amide and 6-iodotryptophan derivatives. X-Ray crystallographic analysis of a β-(indol-6-yl)-leucine derivative confirms the stereochemistry of the cross-linked adduct matches that of the natural products. The method enables the preparation of the Leu-Trp adduct as a single stereoisomer from l-leucine and l-tryptophan. © 2010 CSIRO.