Potassium tert-Butoxide-Mediated Cascade Synthesis of Rutaecarpine Alkaloid Analogues: Access to Molecular Complexity on Multigram Scales

In this study, we present a novel and cost-effective approach for synthesizing biologically significant analogues of rutaecarpine alkaloid through a one-step cascade reaction. The pentacyclic core of rutaecarpine alkaloid analogues is efficiently constructed using 2-aminobenzonitriles and substituted indole-2-carbaldehydes in the presence of the affordable base KOtBu. The salient feature of this approach is the promotion of a sequential cascade process within a single reaction vessel including the formation of a dihydroquinazolinone ring, oxidation, and cyclization. This method can be successfully applied on a larger scale, making it economically viable.