Studies On New Method For Synthesis Of Heterocycles By Multicomponent Reactions Of Isocyanide And Arylglyoxal

The future development direction of pesticide products will be:environment friendly, safe and harmless to humans, high selectivity, low dosage, and the green technological process, namely "green pesticide". Therefore, green synthesis method will also be required of green pesticides. Heterocyclic compounds have shown good prospects in pharmaceuticals and agrochemicals due to their high biological activity, low toxicity and high systemic property. The synthesis of these compounds, the structural transformation and drug activity has always been an trend of organic chemistry and medicinal chemistry research.In this dissertation, we described our works about one-pot synthetic method of divers heterocycles, such as pyrrolidin-5-one,1,2,3,6-tetrahydropyridin-6-one, β-lactam and tetrahydrofuran-5-one, by post-modification of MCRs based on isocyanide and arylglyoxal, and reported the fungicidal and anticancer activity data of the synthesized compounds. It may be summarized as follows:1. The recent application of MCR, including Ugi reaction and Passerini reaction, in heterocyclic synthesis were reviewed.2. A one-pot base-mediated synthesis of5-oxopyrrolidine-2-carboxamides was developed. The reaction of Baylis-Hillman acids, primary amines, arylglyoxals and isocyanides produced the2-aroyl-5-oxopyrrolidine-2-carboxamides6in good yields via a tandem Ugi4CC/SN cyclization at room temperature in the presence of Cs2CO3. As well, we tested antibacterial activity to Gibberella zeae and anticancer activity to HeLa Cell of these compounds, and founded compounds6fa,6fc,6fd and6ff showed good inhibitory activity to HeLa Cell, the IC50values of them were6.2μmol/L,5.4μmol/L,3.7μmol/L and4.9μmol/L, respectively.3. An efficient synthetic approach to1,2,3,6-tetrahydropyridin-6-one-2-carboxamides16has been developed by a domino reaction based on MCR and the hydrolysis of ylide intermediates from Baylis-Hillman Phosphonium salts, primary amines, isocyanides and arylglyoxals in moderate yields in one pot. As well, we tested antibacterial activity to Gibberella zeae of these compounds.4. β-Lactam scaffold was fabricated regioselectively by a facile one-pot base-mediated synthesis. The reactions of a-bromo-carboxylic acids, primary amines, isocyanides and arylglyoxals produced2-aroyl-4-oxoazetidine-2-carboxamide24in good yields via a one-pot tandem Ugi4CC/SN cyclization at room temperature in the presence of Cs2CO3. As well, we tested antibacterial activity to Gibberella zeae and anticancer activity to HeLa Cell of these compounds, and founded compounds 24f,24g and24k showed good inhibitory activity to HeLa Cell, the IC50values of them were24.9μ mol/L,21.0μmol/L and21.8p, mol/L, respectively.5. We described a one-pot base-assisted synthesis of y-lactone28by a tandem Passerini3CC/SN cyclization of Baylis-Hillman acids, arylglyoxals and isocyanides. As well, we tested antibacterial activity to Gibberella zeae of these compounds, and founded compounds28b showed good inhibitory activity to Gibberella zeae under50μg/mL.