Study On Synthesis And Antitumor Activities Of Derivatives Of Deoxypodophyllotoxin

OBJECTIVE:found on the basis of the pre-preliminary pharmacological study of deoxypodophyllotoxin, the deoxypodophyllotoxin has a good anti-tumor activity, but at the same time, according to the toxicity studies, deoxypodophyllotoxin are highly toxic, it is not conducive to the development as anticancer drugs. On this basis, based on the deoxypodophyllotoxin’s parent structure, modify the structure of deoxypodophyllotoxin to get a series of derivatives of the deoxypodophyllotoxin, screen the Anti-tumor activity to obtain the deoxypodophyllotoxin derivatives of the high anti-cancer activity with low toxicity and make the material basis for the development of Anthriscus sylvestris as well as the development of new anti-tumor drugs.METHODS:On the basis of literature research, according to a comprehensive analysis of the relationships between the position of the deoxypodophyllotoxin and the structure-activity, the final choice of the present study is to modify the4’-position, by firstly removal of the methyl group of the4’position of deoxypodophyllotoxin, and estering with different carboxylic acid. Contrasts to derivatives of the previously reported in the literature, using the cyclic carboxylic acids, the esters were synthesized of deoxypodophyllotoxin derivatives. For the content of deoxypodophyllotoxin in Anthriscus sylvestris(L.)Hoffm very low, It is impossible to separate a large amount of deoxypodophyllotoxin as raw material to synthesize the derivatives within a short time. By the catalytic hydrogenation method of removal of the4-position hydroxyl group, a large amount of deoxypodophyllotoxin was synthesized to be used in pharmacological experiments.RESULTS:According to a lot of experiments, optimize the amount of Pd/C and hydrogen pressure to synthesize the deoxypodophyllotoxin from podophyllotoxin. For example, reducing the amount of palladium on carbon and the pressure of hydrogen, relative to other literature reports, the yield does not reduce. The200g deoxypodophyllotoxin was synthesized, whose purity is more than98%detected by HPLC. At the same time, modifying the deoxypodophyllotoxin’s4’-position, five derivatives of the deoxypodophyllotoxin were synthesized, in which four compounds are new.CONLUSION:Optimize the reaction conditions for the synthesis of deoxypodophyllotoxin from podophyllotoxin, synthesize deoxypodophyllotoxin for the pharmacological response and derivatives, and modify the structure of deoxypodophyllotoxin. Synthesized five derivatives of deoxypodophyllotoxin were synthesized, whose anti-tumor activity were studied and found two derivatives with equal activity and nontoxic to the deoxypodophyllotoxin.