Kanno Asahi, Tanifuji Ryo, Yoshida Satoshi, Sato Sota, Maki-Yonekura Saori, Takaba Kiyofumi, Kang Jungmin, Tono Kensuke, Yonekura Koji, Oguri Hiroki
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Applied Chemistry, School of Engineering, The University of Tokyo, FS CREATION, Mitsui LINK Lab Kashiwanoha 1, 6-6-2 Kashiwanoha, Kashiwa, Chiba, 227-0882, Japan.
Beilstein J Org Chem. 2025 Jan 28;21:226-233. doi: 10.3762/bjoc.21.14. eCollection 2025.
The integration of copper(I)-catalyzed three-component coupling with gold(I)-mediated 6- cyclization streamlines the rapid and modular assembly of the substructure of bis-tetrahydroisoquinoline (THIQ) alkaloids. The design of the key synthetic intermediate bearing a 2,3-diaminobenzofuran moiety allows both gold(I)-mediated regiocontrolled 6- hydroamination and temporary protection of nitrile and phenolic hydroxy groups. The synthetic strategy enabled the efficient synthesis of the substructure of saframycins bearing isoquinoline and THIQ units in just four steps from the modular assembly of the three components. We also found the unexpected involvement of a fluorescent intermediate in the cascade synthetic process.
铜（I）催化的三组分偶联与金（I）介导的6-环化反应相结合，简化了双四氢异喹啉（THIQ）生物碱亚结构的快速模块化组装。带有2,3-二氨基苯并呋喃部分的关键合成中间体的设计，既允许金（I）介导的区域控制6-氢胺化反应，又能对腈基和酚羟基进行临时保护。该合成策略仅通过三步组分的模块化组装，就能在短短四步中高效合成含有异喹啉和THIQ单元的saframycins亚结构。我们还发现了一种荧光中间体意外参与级联合成过程。
