Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Bioorg Med Chem. 2024 Nov 1;113:117928. doi: 10.1016/j.bmc.2024.117928. Epub 2024 Sep 16.
Since transition-metal-catalyzed reactions are one of the most powerful and direct approaches for the synthesis of organic molecules, translating them to biological systems for biomedical applications is an emerging field. The manipulation of transition metal reactions in biological settings for uncaging prodrugs and synthesizing bioactive drugs has been widely studied. To expand the toolbox of transition-metal-mediated prodrug strategy, this work introduces the 2'-alkynl-biphenylamine precursors for the synthesis of phenanthridine derivatives using a water-compatible gold-catalyzed hydroamination under mild conditions. Moreover, the structure-reactivity relationship revealed that the nucleophilicity of the amine group in the precursor was critical for facilitating the gold-catalyzed synthesis of phenanthridine derivatives. The research shows the potential to be used for phenanthridine-based prodrug designs in an aqueous solution.
由于过渡金属催化反应是合成有机分子最强大和直接的方法之一，将其转化为生物系统用于生物医学应用是一个新兴领域。在生物环境中操纵过渡金属反应以解笼前药和合成生物活性药物已得到广泛研究。为了扩展过渡金属介导的前药策略的工具包，这项工作引入了 2'-炔基-联苯胺前体，用于在温和条件下使用水兼容的金催化氨化反应合成菲啶衍生物。此外，结构-反应性关系表明，前体中胺基的亲核性对于促进金催化菲啶衍生物的合成至关重要。研究表明，它有可能在水溶液中用于基于菲啶的前药设计。
