Synthesis And Antitumor Activities Of Conjugates Of Podophyllotoxins And Coumarin

This thesis is consisit of two parts: the first part is the synthesis and antitumor activity of conjugates of 4′-demethyl-epipodophyllotoxin and coumarin derivatives;the second part is about the synthetic process of 3-thenoic acid from3-bromothiophene.1.Coumarin,a bicyclic heterocycle consisting of benzene and 2-pyrone ring,exhibit remarkable array of biological properties,such as anti-HIV,antioxidant,anti-inflammatory,antituberculosis,antidepressant activities.Recently,the anticancer activities of coumarin are revealed,however,the defect of poor water-solubility,low bioavailability and unkown mechanism of interactions limitits coumarins used in clinic.Podophyllotoxin has lots of potent activities,exhibiting a promising expectation in antitumor.But podophyllotoxin also shows high toxicity with the normal cells,which limitits its use in clinic.To find novel compounds with potent activities and less toxicity based on natural product,we designed and synthesized a series of conjugates of 4′-demethylepipodophyllotoxins and coumarin derivatives by chemical bridge of 1,2,3-triazole.These compounds showed potent cytotoxic effects on four human tumor cell lines（A549,HeLa,HepG2 and LoVo）,especially compound 75 e exibited the highest cytotoxicities,with IC₅0 values of 4.92–17.48 μM for these four cell lines.Furthermore,compound 75 e interacted with CT DNA induced cell cycle arrest in the G1 phase by regulating level of p21 anf cyclinD1 in LoVo cells.2.3-thiophenecarboxylic acid,a chemical and pharmaceutical intermediate,is commonly used as photographic dye for solar cells.But 3-thiophenecarboxylic acid is expensive in market.In order to find new economic synthetic proceeds for3-thiophenecarboxylic acid,we tried to obtain 3-thiophenecarboxylic acid with3-bromothiophene as the original compound by two methods.The yield reached 76%finally,which will be helpful for mass production of 3-thiophenecarboxylic acid in the future.