Dudawalamides A–D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium <i>Moorea producens</i>

A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A–D (<b>1</b>–<b>4</b>), was isolated from a Papua New Guinean field collection of the cyanobacterium <i>Moorea producens</i> using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A–D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey’s analysis, chiral-phase GCMS, and chiral-phase HPLC. Dudawalamides A–D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure–activity relationship features of these NRPS–PKS-derived metabolites and their derivatives