Department of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Org Lett. 2022 Nov 4;24(43):7894-7899. doi: 10.1021/acs.orglett.2c02870. Epub 2022 Oct 25.
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.
本文报道了一种从头发现的乳唑类硫肽的合成策略。该方法围绕着中心三杂环氨基酸的收敛和可扩展制备展开，并将其用于 Fmoc 固相肽合成，以实现模块化肽链组装。本文还描述了一种用于生物研究的 C 端功能化硫肽的制备技术。以毫克级规模合成了 11 种 TNIK 抑制剂硫肽及其 6 种衍生物，突出了所开发方案的实际应用价值。
