Development of Methods for Convergent Synthesis of Chloroalkene Dipeptide Isosteres and Its Application
Development of Methods for Convergent Synthesis of Chloroalkene Dipeptide Isosteres and Its Application
复制标题
氯烯二肽电子等排体的趋同合成方法开发及其应用
DOI：
10.1021/acs.joc.0c03019
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Tamamura Hirokazu
中科院分区：
文献类型：
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作者：
Kobayakawa Takuya;Azuma Chika;Watanabe Yuki;Sawamura Shunsuke;Taniguchi Atsuhiko;Hayashi Yoshio;Tsuji Kohei;Tamamura Hirokazu
报道了利用氯烯二肽电子等排体（CADI）收敛合成肽模拟物的改进方法。在该合成中，Fmoc-或Boc-保护的羧酸可以通过Evanssynaldol反应从对应于每种氨基酸起始材料的N-和C-末端类似物制备，然后利用Ichikawa烯丙基氰酸酯重排反应进行[3.3] σ迁移重排。利用这种策略，Fmoc保护的CADI可以直接用于固相肽合成。使用这种方法，我们还鉴定了含有CADI的环[-Lys-Leu-Val-Phe-Phe-]肽模拟物，其是比母体肽更好的淀粉样蛋白-β聚集的上级抑制剂。
Improved methods of convergent synthesis for peptidomimetic utilizing a chloroalkene dipeptide isostere (CADI) are reported. In this synthesis, Fmoc- or Boc-protected carboxylic acids can be produced fromN- andC-terminal analogues corresponding to each amino acid starting material via an Evanssynaldol reaction, followed by a [3.3] sigmatropic rearrangement utilizing the Ichikawa allylcyanate rearrangement reaction. With this strategy, an Fmoc-protected CADI can be directly applied for solid-phase peptide synthesis. Using this approach, we have also identified the CADI-containingcyclo[-Lys-Leu-Val-Phe-Phe-] peptidomimetic, which is a superior inhibitor of amyloid-β aggregation than the parent peptide.