Serendipitous Emergence of Pyrrolo[2,3,4-kl]acridin-1(2H)-one Derivatives: From Unexpected Discovery to Synthetic Development.

Serendipitous discoveries have often opened new doors in organic synthesis for the synthesis of unknown reaction paths and molecular frameworks. The well-known method to synthesize acridine derivatives is the classical multicomponent condensation of amines, carbonyl compounds, and 1,3-dicarbonyl compounds. In 2012, Kefayati and coworkers reported the remarkable unprecedented synthesis of pyrrolo[2,3,4-kl]acridin-1(2H)-one derivatives from a multicomponent reaction combining isatin, dimedone, and aniline derivatives. The complex pyrroloacridine scaffold, a motif associated with many natural products and bioactive molecules, was directly synthesized by this unexpected transformation, which was distinct from the traditional synthesis of acridines. Significant advancements have been made in the design of several synthetic approaches for pyrroloacridine derivatives since this landmark discovery. This comprehensive review summarizes the advances covering synthetic approaches, mechanistic insights, and future perspectives.