Enzymatic Synthesis Of 2,3-Dihydroquinazoline-4(1H)-one Derivatives By Protease

2,3-Dihydroquinazoline-4(1H)-one derivatives belong to an important class of nitrogen heterocycles, that attracted much attention because these quinazolinone scaffolds as core unit for a wide spectrum of nature plant alkaloids and pharmacological compounds which comprising quinazolin-4(1H)-one core structure exhibit different biological pharmacological activity. 2,3-Dihydroquinazolin-4(1H)-one derivative as intermediates could be oxidized to the corresponding quinazolin-4(3H)-ones. In recent years, the “green synthesis”has become the mainstream in the organic synthesis, and enzymes have been widely used as green catalysts to catalyze organic synthesis reaction. This paper explored the cyclocondensation of 2-aminobenzamide with aldehydes catalyzed by bio-enzymes, and the new methods of green synthesis of the 2,3-dihydroquinazolin-4(1H)-ones have been discovered. The main contents are as follows:Pepsin-catalyzed synthesis of 2,3-hydrogen-quinazoline-4(1H) derivatives research. The different enzymatic promiscuous ability which to catalyze cyclocondensation of aldehydes with 2-aminobenzamides were researched under alcohol solvent, and pepsin was determined as the best catalyst. The catalytic activity of pepsin was evaluated through investigating the temperature, the enzyme loading and the ratio of substrates in the enzyme catalyzed reaction, and the best reaction conditions were identified: the 5mg pepsin could catalyze aldehydes with 2-aminobenzamides to afforded the corresponding 2,3-dihydroquinazolin-4(1H)-ones successfully in high yields(89%-98%) at 65℃.The research of the synthesis of 2,3-hydrogen-quinazoline-4(1H) derivatives catalyzed by α-chymotrypsin. The eight kinds of proteases were studied to catalyze cyclocondensation of aldehydes with 2-aminobenzamides, and the α-chymotrypsin was determined as the best catalyst. The cyclocondensation of aldehydes with 2-aminobenzamides were catalyzed by α-chymotrypsin for 30-60 min, to afforded the corresponding 2,3-dihydroquinazolin-4(1H)-ones successfully in the yield of 90%-98%. Moreover, the immboilized α-chymotrypsin was used as catalyst, obtained 83% yield of products, and the immboilized α-chymotrypsin could be recycled.The research of the green synthesis of 2,3-hydrogen-quinazoline-4(1H) derivatives under water. The no-catalyzed synthesis of 2,3-dihydroquinazolin-4(1H)-ones by direct cyclocondensation of 2-aminobenzamide with aromatic aldehydes under water at 90℃. This synthetic method has the advantages of with no catalyst, no organic solvents, and high products yield.