Jin Yunhe, Jiang Min, Wang Hui, Fu Hua
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P.R. China.
Sci Rep. 2016 Feb 2;6:20068. doi: 10.1038/srep20068.
Readily available natural α-amino acids are one of nature's most attractive and versatile building blocks in synthesis of natural products and biomolecules. Peptides and N-heterocycles exhibit various biological and pharmaceutical functions. Conjugation of amino acids or peptides with N-heterocycles provides boundless potentiality for screening and discovery of diverse biologically active molecules. However, it is a great challenge to install amino acids or peptides on N-heterocycles through formation of carbon-carbon bonds under mild conditions. In this article, eighteen N-protected α-amino acids and three peptides were well assembled on phenanthridine derivatives via couplings of N-protected α-amino acid and peptide active esters with substituted 2-isocyanobiphenyls at room temperature under visible-light assistance. Furthermore, N-Boc-proline residue was successfully conjugated with oxindole derivatives using similar procedures. The simple protocol, mild reaction conditions, fast reaction, and high efficiency of this method make it an important strategy for synthesis of diverse molecules containing amino acid and peptide fragments.
易于获得的天然α-氨基酸是天然产物和生物分子合成中自然界最具吸引力和多功能性的构建单元之一。肽和N-杂环具有多种生物和药物功能。氨基酸或肽与N-杂环的共轭为筛选和发现各种生物活性分子提供了无限潜力。然而,在温和条件下通过形成碳-碳键将氨基酸或肽安装在N-杂环上是一项巨大的挑战。在本文中,在可见光辅助下,通过N-保护的α-氨基酸和肽活性酯与取代的2-异氰基联苯在室温下的偶联反应,将18种N-保护的α-氨基酸和3种肽很好地组装在菲啶衍生物上。此外,使用类似的方法成功地将N-Boc-脯氨酸残基与氧化吲哚衍生物共轭。该方法操作简单、反应条件温和、反应速度快且效率高,使其成为合成含氨基酸和肽片段的各种分子的重要策略。