Solid-Phase-Based Synthesis of Lactazole-Like Thiopeptides
Solid-Phase-Based Synthesis of Lactazole-Like Thiopeptides
复制标题
乳唑类硫肽的固相合成
DOI：
10.1021/acs.orglett.2c02870
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发表时间：
2022
期刊：
影响因子：
5.2
通讯作者：
Suga Hiroaki
中科院分区：
文献类型：
--
作者：
Zhang Yue;Vinogradov Alexander A.;Chang Jun Shi;Goto Yuki;Suga Hiroaki
本文报道了一种合成新发现的内酰胺唑类硫肽的方法。该方法围绕中心三杂环氨基酸的聚合和可扩展制备及其在Fmoc固相肽合成中的应用，用于模块化肽链组装。还描述了制备用于生物学研究的c端功能化硫肽的技术。11种tnik抑制剂硫肽及其6种多毫克量衍生物的合成突出了所开发方案的实际效用。
A strategy for the synthesis of de novo discovered lactazole-like thiopeptides is reported. The approach revolves around a convergent and scalable preparation of the central triheterocyclic amino acid and its utilization in Fmoc solid-phase peptide synthesis for modular peptide chain assembly. A technique for preparing C-terminally functionalized thiopeptides for biological studies is also described. The syntheses of 11 TNIK-inhibitor thiopeptides and 6 of their derivatives in multimilligram quantities highlight the practical utility of the developed protocols.