Dudawalamides A–D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium Moorea producens

A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A–D (1–4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens 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.一类含有2,2-二甲基-3-羟基-7-辛炔酸（Dhoya）的环酯肽家族，命名为dudawalamides A~D（对应编号1~4），通过生物活性导向分离与光谱学手段，从巴布亚新几内亚野外采集的蓝细菌Moorea producens中分离得到。dudawalamides A~D的平面结构通过一维与二维核磁共振（NMR）实验结合质谱（MS）分析得以解析，其绝对构型则通过X射线晶体衍射、改良马尔菲分析、手性气相色谱-质谱联用（chiral-phase GCMS）以及手性高效液相色谱（chiral-phase HPLC）确定。dudawalamides A~D具有广谱抗寄生虫活性，且对哺乳动物细胞的细胞毒性极低。对含Dhoya的脂肽类家族开展比较分析，可揭示这类由非核糖体肽合成酶-聚酮合酶（NRPS-PKS）衍生的代谢物及其衍生物的构效关系特征。