Construction of functionalized tricyclic dihydropyrazino-quinazolinedione chemotypes via an Ugi/N-acyliminium ion cyclization cascade

• Published in: Tetrahedron letters Vol. 54; no. 33; pp. 4467 - 4470
• Main Authors: Gunawan, Steven, Hulme, Christopher
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 14.08.2013; Elsevier
• Subjects: Alkaloids; Cascades; Chemistry; Chemistry, Organic; Construction; Heterocycles; Libraries; Marine; Multi-component reaction; N-acyliminium ion; Peptidomimetics; Physical Sciences; Science & Technology; Sequences; Synthesis; Tetrahedrons; Ugi reaction; Heterocycles; N-acyliminium ion; Peptidomimetics; Ugi reaction; Multi-component reaction; DIKETOPIPERAZINES; ONE-POT SYNTHESIS; SOLID-PHASE SYNTHESIS; BICYCLIC LACTAMS; STRATEGY; CHEMISTRY; MULTICOMPONENT SYNTHESIS; METATHESIS; ACCESS; multi-component reaction; heterocycles
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2013.06.042

Herein, we report the production of a diversified tricyclic scaffold in 3 synthetic operations involving an Ugi multicomponent reaction followed by an N-acyliminium ion cyclization cascade. Further functionalization of the biologically appealing tricyclic core 24 was achieved via sequential N-alkylation and N-acylation and/or sulfonation. Dihydropyrazino-quinazolinedione chemotypes are complex and structurally challenging structures of biological interest, being found in the marine alkaloids such as brevianamide M–N and fumiquinazolines A–C. Herein we report the synthesis of this tricyclic system in three synthetic operations by means of an Ugi multi-component reaction (MCR) followed by a tandem N-acyliminium ion cyclization-intramolecular nucleophilic addition reaction sequence. Additional structural diversification for further library enrichment was also accomplished via sequential N-alkylation and N-acylation/sulfonation.