Organocatalytic stereoselective synthesis of amino acid-fused quinazolinone based triazacyclic new chemical entities.

Chiral polycyclic quinazolinone scaffolds bearing multiple stereocenters are prevalent in natural products and pharmaceuticals, making their asymmetric synthesis highly desirable. Herein, we report the design and stereoselective synthesis of novel quinazolinone-fused triazacyclic frameworks integrating two biologically significant motifs into a single, densely functionalized scaffold via an efficient, transition metal-free, organocatalytic one-pot protocol. The use of a chiral Brønsted acid catalyst facilitates higher diastereoselectivity, enabling the generation of a diverse library of diastereomerically enriched polycyclic quinazolinone based new chemical entities (NCEs) in good yields under mild conditions. Furthermore, the protocol should be applicable to other imine substrates, offering a potential route to diverse complex molecular scaffolds of pharmaceutical interest.