Synthesis and biological evaluation of a beauveriolide analogue library.
Synthesis and biological evaluation of a beauveriolide analogue library.
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DOI：
10.1021/cc050084d
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发表时间：
2006-03
影响因子：
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通讯作者：
Kenichiro Nagai;T. Doi;Takafumi Sekiguchi;I. Namatame;T. Sunazuka;H. Tomoda;S. Ōmura;Takashi Takahashi
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文献类型：
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作者：
Kenichiro Nagai;T. Doi;Takafumi Sekiguchi;I. Namatame;T. Sunazuka;H. Tomoda;S. Ōmura;Takashi Takahashi
通过使用2-氯三苯甲基接头固相组装线性缩肽，然后进行液相环化，合成了巨噬细胞中脂滴积累抑制剂白僵菌素III（1b）。在此基础上，利用射频编码组合化学技术构建了白僵菌类似物的组合文库。在使用制备型反相HPLC自动纯化后，测试文库在巨噬细胞中CE合成的抑制活性以确定白僵菌内酯的结构-活性关系。其中，我们发现联苯衍生物7{9，1}的效力是1b的10倍。
Synthesis of beauveriolide III (1b), which is an inhibitor of lipid droplet accumulation in macrophages, was achieved by solid-phase assembly of linear depsipeptide using a 2-chlorotrityl linker followed by solution-phase cyclization. On the basis of this strategy, a combinatorial library of beauveriolide analogues was carried out by radio frequency-encoded combinatorial chemistry. After automated purification using preparative reversed-phase HPLC, the library was tested for inhibitory activity of CE synthesis in macrophages to determine structure-activity relationships of beauveriolides. Among them, we found that diphenyl derivative 7{9,1} is 10 times more potent than 1b.