Synthesis of phenanthridine derivatives by a water-compatible gold-catalyzed hydroamination

Abstract

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.