Study On Copper-catalyzed Intermolecular Tandem Synthesis Of 2-acylquinolines From O-aminophenylacetylenes And Glyoxals And Their Pharmaceutical Activity

Quinolines are ubiquitous structural units in biologically active natural products and drugs,among which 2-acylquinolines have been proved to have unique biological activities,such as anticancer activity and antiviral activity.Therefore,the synthesis of2-acylquinoline drugs has important research significance and commercial value.In this paper,o-aminophenylacetylene and glyoxal were used as substrates,cuprous bromide was used as a catalyst,and 2-acylquinolines were synthesized by an intermolecular series cyclization strategy,and preliminary anticancer activity tests were carried out.Specific research contents:(1)Substrate synthesis.The substrate o-aminophenylacetylene compound is prepared from o-aminoiodobenzene compound and trimethyldisilyne through Sonogashira reaction followed by hydrolysis;the substrate glyoxal compound is prepared from methyl ketone compound through oxidation reaction.(2)Exploration of reaction conditions.The optimal reaction conditions were o-aminophenylacetylene and phenylglyoxal as template substrates,piperidine as organic base,cuprous bromide as catalyst,and p-xylene as reaction solvent.(3)Substrate seope.According to the optimal reaction conditions,thirty-six2-acylquinoline compounds were synthesized,showing good universality and reactivity,and the highest yield can reach 86%.(4)Gram-scale experiments and their conversions.This method is practical for the large-scale synthesis of 2-acylquinolines.2-acylquinolines can be synthesized by reduction reaction or cyclization reaction to synthesize methanolic phenylquinolines,indazolones,imidazolines and triazolequinolines,which are of high synthetic value.(5)Research on the reaction mechanism.Through controlled experiments and combined with previous studies,a copper(I)-catalyzed cascade reaction mechanism was proposed.(6)Drug activity research.Twenty-two 2-acylquinoline compounds were selected for preliminary research on their antitumor drug activity,among which(7-methyl-quinolin-2-yl)(phenyl)methyl Ketones,(6-methoxyquinolin-2-yl)(phenyl)methanone and quinolin-2-yl(3,4,5-trimethoxyphenyl)methanone have inhibitory effects on ovarian cancer cells,the number of cells was significantly reduced,the shape was shrunken,rounded and smaller,and it was going to apoptosis,while other drugs showed a promoting effect.This paper successfully developed a green,efficient and simple synthetic route for the synthesis of 2-acylquinoline compounds.This route has good functional group compatibility,among which functional groups such as halogenated,methoxyl,cyano,nitro,and ester groups are all tolerant.Preliminary anticancer activity test studies have shown that some 2-acylquinoline compounds have a certain activity of inhibiting the growth of cancer cells.