Tonakiamides A and B, Antitrypanosomal Lipopeptides Isolated from a Marine Okeania sp. Cyanobacterium

Abstract

The structure elucidation of peptidic natural products is often hindered by extensive N-methylation and repetitive sequence motifs, which complicate NMR spectral analysis. Tonakiamides A and B (1 and 2), two lipopeptides isolated from a marine Okeania sp. cyanobacterium collected in Japan, represent such challenging compounds. Tonakiamides A and B (1 and 2) are acyclic nonapeptides composed of a hexanoic acid moiety and nine amino acid residues, six of which are N-methylated, resulting in complex mixtures of rotamers. Their structures were elucidated through a combination of spectroscopic and spectrometric analyses together with the characterization of three partial hydrolysates obtained under mild hydrolysis conditions. Tonakiamides A and B exhibited moderate growth-inhibitory activities against Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness.