Iron‐Catalyzed Biomimetic Dimerization of Tryptophan‐Containing Peptides
Iron‐Catalyzed Biomimetic Dimerization of Tryptophan‐Containing Peptides
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铁催化含色氨酸肽的仿生二聚
DOI：
10.1002/anie.202302404
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Tokuyama Hidetoshi
中科院分区：
文献类型：
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作者：
Ueda Hirofumi;Sato Soichiro;Noda Kenta;Hakamata Hiroyuki;Kwon Eunsang;Kobayashi Nagao;Tokuyama Hidetoshi
以氧为主体氧化剂，八羧基铁酞菁配合物为催化剂，建立了色氨酸衍生物在水相中的仿生氧化二聚反应。活性极高的铁催化剂的发现使得在烧瓶中进行有氧酶模拟氧化成为可能。该方法适用于各种色氨酸衍生物的氧化二聚，包括各种二肽和寡肽，具有显著的官能团耐受性，而无需保护氨基酸残基。此外，氧化二聚色氨酸衍生物轴承二氧哌嗪单元，使收敛全合成五个天然吡咯并吲哚化合物和非天然同系物。已建立的化学方法提供了方便的途径来获得广泛的二聚肽，其具有独特的支架来连接两个转弯结构，这将成为创建新的小分子和中等大小的分子作为候选药物的有力工具。
Biomimetic oxidative dimerization of tryptophan derivatives in aqueous media with oxygen as a bulk oxidant catalyzed by an iron octacarboxy phthalocyanine complex was established. The discovery of the extremely active iron catalyst enables aerobic enzyme‐mimetic oxidation to be performed in a flask. This method was applicable to the oxidative dimerization of a wide range of tryptophan derivatives, including various dipeptides and oligopeptides, with remarkable functional‐group tolerance without the protection of the amino acid residues. Furthermore, oxidative dimerization of tryptophan derivatives bearing dioxopiperazine units enabled the convergent total synthesis of five natural pyrroloindole compounds and unnatural congeners. The established chemical method provides facile access to a broad range of dimerized peptides with a unique scaffold to link two turn structures, which will serve as a powerful tool to create new small‐ and medium‐sized‐molecules as drug candidates.