Studies On The Synthesis,Characterization And Cytotoxic Activities Of 13-cis-Retinoyl Ferrocene Derivatives

Both Ferrocene and 13-cis-Retinoyl acid have strong cytotoxic activity against cancer cells. At present, they have been used widely in the field of medicine and clinical treatment. This thesis is mainly about the work of synthesis of 13-cis-Retinoyl Ferrocene Derivatives and test of their cytotoxic activities. Three parts are contained in this thesis as follows:1. A series of ferrocene alcohols and phenols 1-10 were synthesized according to the typical reactions of ferrocene, and their structures were characterlized, these compounds have potential cytotoxic acitivities and can be used as reactants in the next step. During the synthesis work, three ferrocene alcohols 8-10 were synthesized through Suzuki reaction with high yield of production successfully. The middling product ferrocene boric acid whose toxicity is small can be prepared very easily. So Suzuki reaction is a convenient new method to combine ferrocene with other substances.2. In order to decrease toxicities of retinoids, enhance physiological Activities against cancer cells and increase absorbency in the organisms, nine novel 13-cis-Retinoyl Ferrocene Derivatives 11-19 that have cytotoxic activity were synthesized through Mitsunobu reaction and their structures were characterized Mitsunobu reaction have many advantages on the synthesis of such compounds as following: (1) The environment of reaction is mild, It inherits the advantage of DCC/DMAP method, the structure of 13-cis-Retinoyl was not changed. (2) The reaction time is 20-22h shorter than DCC/DMAP method. (3) The yield of production is higher than 80%. Compared to DCC/DMAP method, it is 30% higher. (4) Resolved the problem that the products and by-products were hard to separate becasuse their polarity is similar in the DCC/DMAP method.3. The cytotoxic activities of the compounds that were synthesized in part 2 and part 3 were determined in vitro by MTT assay using human cancer lines including A549 cells,BEL7407 cells and Tca cells lines. Results showed that all the compounds have cytotoxic activities and the 13-cis-Retinoyl Ferrocene Derivatives that were modified by ferrocene groups exhibited more excellent cytotoxic activities against cancer cells than reactants.19 compounds were synthesized in this thesis, ten were ferrocene alcohols and phenols, nine were 13-cis-Retinoyl Ferrocene Derivatives.