Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia:: isolation, structure determination, synthesis, and biological activity
Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia:: isolation, structure determination, synthesis, and biological activity
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DOI：
10.1016/j.tet.2004.06.125
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发表时间：
2004-09-13
期刊：
影响因子：
2.1
通讯作者：
Yamada, K
中科院分区：
文献类型：
--
作者：
Suenaga, K;Mutou, T;Yamada, K
通过对日本海兔DolLabella aurceraria的细胞毒性成分进行生物测定指导的分离，得到了26个成员的环磷脂肽(1)。通过波谱分析，包括二维核磁共振技术，确定了1的大体结构。绝对立体结构是通过手性高效液相分析1的酸性水解物和通过对二羟基脂肪酸部分产生的降解产物的对映选择性合成来确定的。1以12%的总收率(16步)完成了对映体选择性合成，证实了1的绝对立体结构。合成的样品对HeLa S-3细胞具有较强的细胞毒作用，IC50为0~011ug/mL。进一步的生物学和药理研究已经使用合成的1。(C)2004年爱思唯尔有限公司。版权所有。
The bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dollabella auricularia led to the isolation of aurilide (1), a 26-membered cyclodepsipeptide. The gross structure of 1 was established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1 and by the enantioselective synthesis of a degradation product arising from a dihydroxylated fatty acid portion. The enantioselective synthesis of 1 was achieved in 12% overall yield (16 steps) and confirmed the absolute stereostructure of 1. The cytotoxicity of 1 was evaluated using a synthetic sample, which was found to exhibit potent cytotoxicity against HeLa S-3 cells with an IC50 of 0-011 mug/mL. Further biological and pharmacological studies of I have been carried out by using synthetic 1. (C) 2004 Elsevier Ltd. All rights reserved.