Synthesis Of Quinazolinones And β-Carbolines Catalyzed By Metal Oxide Nanoparticals

Quinazolinones and β-Carbolines were two kinds of ubiquitous compounds which belong to N-fused heterocycles. They played an important role in medicinal chemistry and had been reported of broad-spectrum bioactivities. The development of an efficient method to synthesize heterocycles was an active research area. Recently, the metal oxide nanoparticles exhibited a good catalytic activity when applicated on the construction of N-fused heterocycles. In this thesis, new metal oxide nanoparticles-catalyzed methods have been developed for synthesis of quinazolinone and metyl-β-carboline-3-carbonate derivatives.A facile and efficient metal oxide nanoparticles-catalyzed one-pot reaction has been developed for synthesis of 3-acylaminoquinazolinone derivatives from isatoic anhydride, benzhydrazide and aldehyde. The protocol was carried out under mild conditions with satisfied product yield by using CeO2 nanoparticles as catalyst, and ethanol as solvent.35 Quinazolinone derivatives containing 3-acrylamino motif were obtained in good to excellent yield. This process performed simple and easy operation, using minor amount of catalyst and high substrate tolerance. The practical method provides a useful strategy for synthesis of quinazolinone derivatives. Four phytopathogenic fungi were chosen to test the antifungal activities of 36 3-acrylamino quinazolinone derivatives. The results presented that most compounds showed a mild activity against each of the fungi (MIC value minimum up to 32 μg/mL). The structure and relationship (SAR) study showed the amide moiety in the compounds was crucial for the activities. Docking studies were established and verified the important interaction between the amide moiety and the protein, and also preliminary explaned the potential antifungal mechanism of these derivatives.A convenient and efficient metal oxide nanoparticles-catalyzed method has been developed via reaction of isatoic anhydride,2-formylbenzoic acid and hydrazides or aromatic hydrazines. The protocol employed TiO2 nanoparticles as catalyst and aqueous ethanol (EtOH/H2O=1:1, v/v) as solvent.16 Isoindolo[2,1-a]quinazoline derivatives and phthalazino[1,2-b]quinazoline-5,8-dione derivatives were obtained in good to excellent yield. The method carried out under mild condition and presented a novel and useful approach for the synthesis of the two kinds of fused quinazolinones.A new metal oxide nanoparticles-catalyzed one-step method has been developed for the synthesis of β-carboline derivatives. The protocol used CuO nanoparticles as the catalyst, readily available methyl L-Tryptophan methyl ester and substituted aldehydes as the starting materials and aqueous ethanol (EtOH/H2O=1:1, v/v) as solvent. The cyclization-dehydrogenation reaction was performed well under mild conditions under air condition without addition of any ligand or additive.11 Target compounds were obtained. This practical method showed advantages as facile and efficient catalyst system, environmental friendly solvent and oxidant from air. The method has provided a new strategy for the synthesis of β-carboline derivatives.