Total Synthesis and Stereochemical Revision of the Anti-Tuberculosis Peptaibol Trichoderin A

Abstract

The first total synthesis of the postulated structure of the aminolipopeptide trichoderin A and its epimer are reported. A late-stage solution phase C-terminal coupling was employed to introduce the C-terminal aminoalcohol moiety. This methodology provides a foundation to prepare analogues of trichoderin A to establish a structure-activity relationship. NMR spectroscopic analysis established that the C-6 position of the 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (AHMOD) residue in trichoderin A possesses an (R)-configuration as opposed to the originally proposed (S)-configuration.