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Updated: May 5, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Formal [2 + 2 + 1 + 1] Annulation Enabled Synthesis and Anti-inflammatory Evaluation of Dimeric
Kai-Lu Zheng1,2, Mei-Yin Wu1,2, Wen-Wen Li1,2
1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523710, P. R. China.
Abstract:
This work presents a facile, metal-free, and atom-economical synthesis of pyrimido[2,1-a:4,3-a']diisoquinolines via an acid-promoted formal [2 + 2 + 1 + 1] annulation of readily available 1,2,3,4-tetrahydroisoquinoline and arylglyoxal monohydrates. This annulation proceeds through an azomethine ylide intermediate, achieving the direct N-H/α-C(sp3)-H difunctionalization of 1,2,3,4-tetrahydroisoquinolines and concurrent formation of multiple C-C and C-N bonds. The resulting polycyclic scaffolds are readily transformed into multifunctional photoluminescent materials that display aggregation-induced delayed fluorescence (AIDF) emission. Preliminary biological evaluation revealed that several derivatives potently inhibit key inflammatory mediators in lipopolysaccharide-activated macrophages, indicating their potential as promising anti-inflammatory lead candidates.
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