Total synthesis of natural benzoazepinoquinolinone alkaloid irrepairzepine via Au(I)-catalyzed cycloisomerization and regioselective functionalization

Abstract

Irrepairzepine (1), a unique benzoazepinoquinolinone alkaloid isolated from an endophytic fungus, exhibits synthetic lethality targeting in PTEN-deficient glioblastoma cells. Herein, the first synthesis of irrepairzepine was achieved through a series of high-yielding reactions. The key steps include the synthesis of quinoline via the Au(I)-catalyzed cycloisomerization of N-propargyl aniline and construction of the azepinone core through the acid-catalyzed lactamization of an aminophenyl cyanoquinoline precursor, which was prepared using a simple umpolung approach that involves regioselective bromination followed by the Rosenmund-von Braun reaction.