Total Synthesis Of Six Coumarins And Evaluation Of Its Antioxidant And Antitumor Activities

Coumarins are lactones which are widely occurring in plants,they have anti-HIV,antitumor,antimarlarial activities.However,their contents in plants are very low and the process of their extraction and purification is complex.To improve the yields of synthetic coumarins and reduce the cost of production,we use benzaldehyde derivatives as the commercially starting materials,via pivaloyl chloride protect the hydroxyl group of the phenols,then iodide the intermediates by N-iodosuccinimide,hydrolysis of the aromatic iodide,ring-closure via the Wittig reaction at last.We gain five naturally occurring coumarins,namely isofraxidin 1,scopoletin 2,6,7,8-trimethoxycoumarin 4,scoparone 5,daphnetin 6 and one synthetic coumarin 6-ethoxy-7-hydroxycoumarin 3.In addition,five important intermediates 2,4-dihydroxy-3,5-dimethoxybenzaldehyde 16,2,4-dihydroxy-5-methoxybenzaldehyde 17,5-ethoxy-2,4-dihydroxybenzaldehyde 18,2-hydroxy-3,4,5-trimethoxybenzaldehyde 23,2-hydroxy-4,5-dimethoxybenzaldehyde 24 were gained.We analyze these comounds by 1H NMR,13C NMR,IR and MS.The yields of most of the coumarins are improved compared literature reports.We use Vitamin C as comparative to evaluate the DPPH radical scavenging activity of these coumarins,the results turned out that all the coumarins are less active than Vitamin C,however,isofraxidin and daphnetin are relatively higher than other couamrins.We use MTT method to evaluate the antitumor activity of the coumarins,7-hydroxycoumarins as comparative.We draw a conclusion that,all the coumarins showing concentration dependent activity and selectivity against different cancer cells.For prostate cancer cells PC-3,the IC50 values of coumarin 1 and 5 are smaller than 7-hydroxycoumarin.For hepatoma cells 7721,the IC50 values of coumarin 2,3,4 are smaller than 7-hydroxycoumarin.For breast cancer cells MCF-7,the IC50 values of coumarin 3 and 6 are smaller than 7-hydroxycoumarin.