Indeno Bicyclopyrrole Synthesis And 2-substituted Heterocyclic Ketene Indanone Amines

Bicyclic pyrroles possess anti-tumor, anti-bacterial, anti-inflammatory and analgesic drug activity, and so on. Pemetrexed, moxifloxacin, zopiclone and other drugs also contain the structures of bicyclopyrroles unit. The indanones have been found in natural products, drugs, pesticides and other biologically active molecules, exhibiting anti-tumor, anti-hypertensive, anti-allergy and other excellent biological activity. Therefore, the synthesis of bicyclic pyrroles and indanones have attracted more and more widely attention.The benzoyl substituted mercaptals2were synthesized by acetophenone derivatives1. Compound2were then reacted with ethane-1,2-diamine, propane-1,3-diamine, butane-1,4-diamine or cyclohexanediamine to obtain heterocyclic ketene amine3(3a-3t).To the heterocyclic ketene amine as blocks, the main research contents and results were as follows:1. In this thesis, cheap and easily available ninhydrin4and heterocyclic ketene amine3were used as raw materials. Twenty novel target compounds indenobicyclic-pyrroles5a-5t (A series) were synthesized in EtOH and under room temprature conditions, the yield was88-97%.2. Ninhydrin4and heterocyclic ketene amine3g,3k were also used as raw materials to react with alcohols6or anilines7which catalyzed by acid conditions to get eighteen O-alkyl substituted and N-aryl amines substituted indenobicyclicpyrroles8a-8r (B series) with three-component and one-pot synthesis protocol, the yield was85-93%.3.1,3-indandione9, ethyl orthoformate10and heterocyclic ketene amine3were refluxed under solvent-free condition to obtain ten novel2-indanone substituted heterocyclic ketene amines11a-11j by one step method, the yield was81-92%.4. The synthetic methods above had the advantages of readily available raw materials, simplicity and efficiency, stable product.5. The in vitro anti-cancer activity of2-indanone substituted heterocyclic ketene amine were were studied on five types of cell lines. The results showed three compounds had good inhibitory activity on human lung adenocarcinoma cell line.6. The synthesized compounds have not been seen in the literature, all the target compounds were characterized by IR,1H NMR,13C NMR and HR-MS.