Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Yoshida, Kyoto, 606-8501, Japan.
Chemistry. 2022 Jun 27;28(36):e202201120. doi: 10.1002/chem.202201120. Epub 2022 May 26.
Conventional methods for the construction of dehydroamino acids (ΔAAs), which are a unique class of non-proteinogenic amino acids, require the pre-installation of special amino acids. Herein, we report and demonstrate the practical utility of an N-chloropeptide strategy for the rapid construction of ΔAA-containing peptides. The electrophilic N-chlorination of peptide bonds is drastically accelerated by a catalytic amount of quinuclidine (ABCO), and the subsequent β-elimination of N-chloroamide efficiently provides ΔAA-containing peptides in high yield. The strategy enables, for the first time, the construction of a wide variety of ΔAA residues in peptides without any pre-functionalized side chains and facilitates the late-stage installation of ΔAA motifs into already-constructed oligopeptides, including a medicinally important macrocyclic peptide.
常规方法用于构建去氢氨基酸（ΔAAs），这是一类独特的非蛋白质氨基酸，需要预先安装特殊的氨基酸。在这里，我们报告并展示了 N-氯肽策略在快速构建含 ΔAA 肽中的实际应用。肽键的亲电 N-氯化作用被催化量的奎宁环（ABCO）大大加速，随后的 N-氯酰胺的 β-消除反应有效地以高产率提供含 ΔAA 的肽。该策略首次能够在不使用任何预功能化侧链的情况下在肽中构建各种 ΔAA 残基，并有利于在已经构建的寡肽中晚期安装 ΔAA 基序，包括一种具有医学重要性的大环肽。
