One-pot Switchable Syntheses Of Quinolone Derivative By Base

Quinolone has been widely used in antibacterial drugs,which plays an important role in the treatment of anti-bacterial infection.Additionally,Quinolone also exhibited anticancer and antimalarial biological activities.Consequently,there are potential values in the development of new with better efficacy and lower toxicity to modify the structure of quinolone.At present,there are many synthetic methods for quinolone derivatives reported in the literature.One of the classical methods uses aniline derivatives and ethyl ?-formylphenylacetate as raw materials,after Friedele-Craft acylation,condensation reaction,acetylation reaction,rearrangement and cyclization reaction to synthesize the target compound,this method requires multiple steps of synthesis,and the operation is cumbersome.Another synthetic method uses a metal(such as Pd,Ni,etc.)catalyst to rapidly synthesize the target compound.This method has fewer synthetic steps,but the reaction process uses anhydrous anaerobic operation,which limits the synthesis of the target compound in large quantities.Therefore,the development of efficient and economical new strategies is still receiving widespread attention.This study is based on a one-pot synthesis strategy that reduces the reaction steps and increases the reaction yield.And for the first time,the benzyl group was inserted between the aldehyde group and the imidazole group in 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde,and two different quinolin-4-ones derivative were constructed:(1)Starting from 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde 1 and benzyl bromide,bromobenzyl was reacted with compound 1 to synthesize the intramolecular Breslow intermediate.If there is a base,Breslow intermediate attacks the phenyl bromide at the 1-position carbon atom by the enol pathway to synthesize the key intermediate I.The intermediate I continues to be converted into the final product benzo[4,5]imidazo[1,2-a]quinoline-5(7H)-one derivative 2.(2)If there is no base involved in the reaction after synthesis,the benzylation would happen at the 2-position of Breslow intermediate via a NHC process to produce intermediate II.Under the catalysis of the base DBU,a ring opening reaction occurs to synthesize the compound 3-arylquinolin-4-one 3.These methods can be used to rapidly and efficiently synthesize quinolones,and these methods have been shown to have good substrate suitability in substrate extension experiments.At the same time,these methods may be used to efficiently construct nitrogen-containing heterocycles to find and develop biologically active lead compounds.The compounds 2a-2i,2k,2o-2q,2r,2u were tested for their cytotoxic antivities for MDA-MB-231,C4-2B and MG803.Among the tested compounds,compounds 2i and 2q displayed potent cytotoxic activities against C4-2B,and compounds 2a-2d,2f-2k,2p-2q exhibited potent inhibition against MG803.Figure [234] table [9] reference [55]...