Tan Lik Tong, Sitachitta Namthip, Gerwick William H
College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
J Nat Prod. 2003 Jun;66(6):764-71. doi: 10.1021/np020492o.
The guineamides (1-6) are novel cyclic depsipeptides isolated and characterized from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. The planar structures of these new natural products were established using an extensive array of 1D and 2D NMR experiments, including HSQC, TOCSY, and HMBC. Absolute stereochemistry was determined using a combination of chemical manipulations as well as Marfey's method. These metabolites all contain beta-amino or beta-hydroxy carboxylic acid residues, an increasingly common feature in marine cyanobacterial metabolites. The identification of 2,2-dimethyl-3-hydroxyhexanoic acid (Dmhha) in guineamides E (5) and F (6) represents the first report of such a residue in a natural product. In addition, characterization of the unique beta-amino acid 2-methyl-3-aminopentanoic acid (Mapa) in guineamide A (1), which has also been reported as a component of several marine molluscan metabolites, especially from those of Dolabella auricularia, further supports the diet-derived nature of such compounds as isolated from marine invertebrates. Guineamides B (2) and C (3) possess moderate cytotoxicity to a mouse neuroblastoma cell line with IC(50) values of 15 and 16 microM, respectively.
几内亚酰胺（1 - 6）是从巴布亚新几内亚采集的海洋蓝藻巨大鞘丝藻中分离并鉴定出的新型环缩肽。这些新天然产物的平面结构通过一系列广泛的一维和二维核磁共振实验得以确定，包括异核单量子相干谱（HSQC）、全相关谱（TOCSY）和异核多键相关谱（HMBC）。绝对立体化学通过化学操作以及马尔菲法相结合的方式确定。这些代谢产物均含有β - 氨基或β - 羟基羧酸残基，这在海洋蓝藻代谢产物中是越来越常见的特征。在几内亚酰胺E（5）和F（6）中鉴定出2,2 - 二甲基 - 3 - 羟基己酸（Dmhha），这是该残基在天然产物中的首次报道。此外，几内亚酰胺A（1）中独特的β - 氨基酸2 - 甲基 - 3 - 氨基戊酸（Mapa）的表征，该氨基酸也被报道为几种海洋软体动物代谢产物的组成部分，尤其是来自耳状芋螺的代谢产物，进一步支持了从海洋无脊椎动物中分离出的此类化合物源自饮食的性质。几内亚酰胺B（2）和C（3）对小鼠神经母细胞瘤细胞系具有中等细胞毒性，其半数抑制浓度（IC50）值分别为15和16微摩尔。
