Total Synthesis of Racemic Benzomalvin E, a Quinazolinone Isolated from Pencilium sp. FN070315 and Exploration to the Direct Synthesis of (E)-Benzomalvin B

We present the first total synthesis of (+/-) benzomalvin E, featuring a quinazolino moiety with a 6-6-6-7-fused tetracyclic skeleton containing three nitrogen atoms. The key transformation involves Cu-catalyzed intramolecular C-N arylation of quinazolinone, leading to a sclerotigenin analogue that undergoes nucleophilic addition with benzaldehyde, enabling the synthesis of (+/-) benzomalvin E in six linear steps with a 33% overall yield. The (+/-) benzomalvin E's structure was validated by 2-D NMR and single crystal XRD analysis and was further transformed into (E)-benzomalvin B.