Studies On Synthesis Of Bioactive Coumarins And Their Aminoalkyl Derivatives

Natural products coumarins are widely used in medicine,chemical fluorescence detection and other fields.As a medicinal natural active compound,the study of structural modification and biological activity of coumarin has always been the focus of research.By introducing active groups into coumarin nucleus,coumarin can be endowed with new structure and connotation.Osthol is a kind of low toxic natural drug.The introduction of isopentenyl has been the key to the synthesis of osthol.In this paper,one compound was synthesized from resorcinol,which is of similar structure with osthol.Moreover,a series of coumarin amino alkyl derivatives were obtained by Hofmann alkylation,which enriched the content of bioactive coumarin derivatives.1.One kind of osthol analogs was total synthesized from resorcinol.The product showed strong inhibitory activity against human cervical cancer Hela cells in the biological activity test in vitro.The key steps of total synthesis were also optimized.And it was found that Florisil catalysis was expected to be a new method for introducing isopentenyl group into coumarin.2.Bromoethoxycoumarin was prepared from 4-methylumbelliferone,then reacted with different secondary amines.Seven coumarin-amine ethoxyl derivatives were obtained by Hofmann alkylation.It is found that the steric hindrance has a great influence on the reaction.Compared with the reaction of dibromobutane with coumarin,dibromoethane is more difficult to react with coumarin,which reaction needs higher temperature.Compared with the reaction of bromobutene coumarin with secondary amine,the yield of coumarin-amine ethoxyl derivatives decreased under the same reaction conditions with more time.A good yield can be obtained better with the temperature increased by 10?.3.Four kinds of coumarin amino acid derivatives were synthesized by the reaction of bromoxyn coumarin and different amino acid methyl ester hydrochloride.It was found that the release of HCl from amino acid methyl ester hydrochloride had a great influence on the reaction yield.Therefore,the removal method of acid was optimized.By analyzing the selection of solvent,temperature in the experiment,a method for synthesizing the coumarin amino acid derivative is obtained.