Synthesis and biological evaluation of analogues of the marine cyclic depsipeptide obyanamide
Synthesis and biological evaluation of analogues of the marine cyclic depsipeptide obyanamide
复制标题
海洋环缩酚酸奥苯酰胺类似物的合成及生物学评价
DOI：
10.1002/psc.1361
复制
发表时间：
2011-07-01
影响因子：
2.1
通讯作者：
Li, Yingxia
中科院分区：
文献类型：
--
作者：
Zhang, Wei;Ding, Ning;Li, Yingxia
在全合成obyanamide的基础上，通过Z/OtBu法在西半球制备三肽片段，Boc/OMe法在东半球制备二肽片段，并在此基础上合成了20个海洋环缩肽类似物。和（iii）在最后一步中进行片段偶联、去除保护基（Boc和OtBu，在一锅中）和大环化。细胞毒性试验表明，三种合成化合物对HL-60、KB、LOVO和A549细胞系表现出中等活性。根据结果，发现β-氨基酸残基在生物活性中起关键作用。此外，酯键沿着与Ala（Thz）部分也是必不可少的生物活性。然而，得出瓦尔/Phe的N-甲基化可导致更高或更低的细胞毒活性的结论似乎还为时过早。版权所有© 2011欧洲肽协会和约翰威利父子有限公司。
On the basis of the total synthesis of obyanamide, 20 analogues of this marine cyclic depsipeptide have been synthesized by (i) preparation of the tripeptide fragments in the western hemisphere using Z/OtBu protocol; (ii) preparation of the dipeptide fragments in the eastern hemisphere using Boc/OMe protocol; and (iii) fragments coupling, removal of protecting groups (Boc and OtBu, in one pot), and macrocyclizaion in the last step. The cytotoxic test showed that three synthetic compounds exhibited moderate activities against HL‐60, KB, LOVO, and A549 cell lines. According to the results, the β‐amino acid residue was found to play a critical role in the biological activities. Additionally, the ester bond along with the Ala(Thz) moiety was also essential for biological activities. However, it seems too early to draw a conclusion that the N‐methylation of Val/Phe can lead to higher or lower cytotoxic activities. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.