Solid phase library synthesis of cyclic depsipeptides: Aurilide and aurilide analogues
Solid phase library synthesis of cyclic depsipeptides: Aurilide and aurilide analogues
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DOI：
10.1021/cc020091r
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发表时间：
2003-07-01
影响因子：
--
通讯作者：
Bray, AM
中科院分区：
文献类型：
--
作者：
Takahashi, T;Nagamiya, H;Bray, AM
描述了环状缩酚酸肽金内酯（1）及其类似物的固相组合合成方法。使用Fmoc策略将肽部分2组装在三苯甲基接头官能化的SynPhase Crowns上。使用平行多重合成和LC/MS分析进行四肽组装体5的优化。使用DIC/ HOBt将脂肪族部分3a与固载2偶联。在线性前体26的脱保护和裂解之后，在高稀释条件下实现大环化。除去甲硫基甲基保护基得到金内酯（1），总收率11%。使用TranSort技术，用类似的方案完成奥瑞内酯衍生物4的组合文库的合成。
A solid-phase combinatorial synthesis approach toward the cyclic depsipeptide aurilide (1) and related analogues is described. The peptide moiety 2 was assembled on trityl linker-functionalized SynPhase Crowns using an Fmoc strategy. Optimization of the tetrapeptide assembly 5 was carried out using parallel multiple synthesis and LC/MS analysis. The aliphatic moiety 3a was coupled with the solid-supported 2 using DIC/ HOBt. Following deprotection and cleavage of linear precursor 26, macrocyclization was achieved under high dilution conditions. Removal of the methylthiomethyl protecting group provided aurilide (1) in 11% overall yield. Synthesis of a combinatorial library of aurilide derivatives 4 was accomplished with a similar protocol using the TranSort technique.