Isolation, structure determination, and biological activity of lyngbyabellin A from the marine cyanobacterium Lyngbya majuscula
Isolation, structure determination, and biological activity of lyngbyabellin A from the marine cyanobacterium Lyngbya majuscula
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DOI：
10.1021/np990543q
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发表时间：
2000-05-01
影响因子：
5.1
通讯作者：
Mooberry, SL
中科院分区：
文献类型：
--
作者：
Luesch, H;Yoshida, WY;Mooberry, SL
Lyngbyabellin A(1)是一种具有显著细胞毒性的化合物，具有不同寻常的结构特征，从关岛的海洋蓝藻Lyngbya majuscula菌株中分离出来。这种新型肽在结构上与dolabellin(2)相关，因为这两种肽都含有一个二氯-羟基酸和两个功能化的噻唑羧酸单位。其总体结构已通过光谱分析，包括二维核磁共振技术阐明。通过水解产物的手性高效液相色谱分析和降解产物甲基7,7-二氯-3-羟基-2,2-二甲基辛酸酯(3)及其相应的酸4的表征，确定了1的绝对立体化学性质。分子模型研究进一步支持了总结构。从L. majuscula中分离到1再次支持了许多最初从海洋中分离到的化合物是蓝藻起源的建议。Lyngbyabellin A(1)被证明是细胞微丝网络的有效破坏者。
Lyngbyabellin A (1), a significantly cytotoxic compound with unusual structural features, was isolated from a Guamanian strain of the marine cyanobacterium Lyngbya majuscula. This novel peptolide is structurally related to dolabellin (2) in that both depsipeptides bear a dichlorinated beta-hydroxy acid and two functionalized thiazole carboxylic acid units. Its gross structure has been elucidated by spectral analysis, including 2D NMR techniques. The absolute stereochemistry of 1 was determined by chiral HPLC analysis of hydrolysis products and by characterization of the degradation products methyl 7,7-dichloro-3-hydroxy-2,2-dimethyloctanoate (3) and the corresponding acid 4. The total structure was further supported by molecular modeling studies. The isolation of 1 from L. majuscula once more supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are of cyanobacterial origin. Lyngbyabellin A (1) was shown to be a potent disrupter of the cellular microfilament network.