Study On The Synthesis And Antibacterial Activities Of 4, 7-Dihydroxycoumarin Derivatives

Coumarins are a kind of natural compounds exhibiting extensive biological activities. Many coumarins with antibacterial activities are extracted from narural plants.In order to find new coumarins being have antibacterial activities and investigate structure-activity relationships,we report the synthesis and antibacterial activities of 4,7-dihydroxycoumarin derivatives.1.The simple and best feasible synthetic routes of 4,7-dihydroxycoumarin derivatives were proposed.We used resorcinol and cyanoacetic as materials,and then it was get the key intermediate 4,7-dihydroxycoumarin(2) by Pechmann reaction and hydrolyzation with yield of 31%.4-methoxy-7-hydroxycoumarin(3) and 4-ethoxy-7-hydroxycoumarin(5) were synthesized from 4,7-dihydroxycoumarin(2) by etherization reaction with yield of 82%and 71%.Later,nineteen 4,7-dihydroxycoumarin derivatives,that is 4-methoxy-7-alkyloxy coumarins(4a-4i),4-ethoxy-7-alkyloxycoumarins(6a-6i) and 4-ethoxy-7-methoxycoumarin (8) were synthesized from 4-methoxy-7-hydroxycoumarin(3) and 4-ethoxy-7-hydroxy coumarin(5) with tetrabutyl ammonium bromide(TBAB) as the phase transfer catalyst by Williamson reaction with yield of 57%-95%.4,7-dimethoxycoumarin(7) was synthesized from 4,7-dihydroxycoumarin(2) by Williamson reaction with yield of 80%.On the basis of the designation,twenty four compounds were synthesized,including four intermediates and twenty target compounds(two series),in these compounds twenty were novel compounds. All of the synthesized compounds were confirmed by IR,MS and ~1H NMR.2.Synthesis route of the key intermediate 4,7-dihydroxycoumarin(2) has been studied. The yield of route 1 use resorcinol and malonc acid with anhydrous zinc chloride and phosphorus oxychloride as catalysts and route 2 use resorcinol and malonic acid with boron trifluoride etherate as catalyst were very low.So we adopted Pechmann reaction and hydrolyzation to synthesis 4,7-dihydroxycoumarin(2).We also determined the effect of reaction time,temperature and the dosage of TBAB on Williamson reaction.Optimum conditions for Williamson reaction were:in DMF,n(3) or n(5):n(alkylhalides):n (anhydrous potassium carbonate):n(TBAB)=1:1.5:2.5:0.1,reacting at 60℃-80℃for 10h -27h. 3.Antibacterial activities.The antibacterial activities of some synthesized coumarins against Rhizoctonia solani,Fusarium graminearum,Botrytis cinerea Pers,Phytophara capsici,Alternaria solani and Xanthomonas oryzae pv.oryzae were analysed.The rusults showed that some coumarins were active in against plant fungus pathogens.Among them, 4-methoxy-7-ethoxycoumarin(4a) has the strongest antibacterial activities against Xanthomonas oryzae pv.oryzae.