| Chalcone is a kind of flavonoid natural products which exists widely in the roots, leaves and pericarps of glycyrrhiza or safflower plants.They have various biological activities such as anti-HIV, anti-inflammation, anti-tummor and so on, as well as its many series of derivatives due to the structure of α,β-ketene with flexibility. However, the low absorption and poor solubility expressed in human body limits its direct application in clinic. Thus, our research group devoted ourself to the modification of the chalcones’molecules by introducing the nitrogen groups to the skeleton via Mannich reaction or Hofmann alkylation reaction in purpose. We also discovered more potential synthetic methods for obtaining polymethoxyflaones （PMFs）, treated as be biological activities-rich. In this thesis, a series of polymethoxychalcones derivatives with nitrogen groups were synthesized and their antiproliferative activities on a panel of three human cancer cell lines were evaluated. The path of synthesizing polyoxymethchalcones was explored in variety, total-synthesis or semi-synthesis, for the further study on PMFs.1.2-Hydroxy-4,6-dimethoxyacetophenone was synthesisd via Friedel-Crafts acetylization and O-methylation with phloroglucinol as a starting compound. Then, 2’-hydroxy-3,4,4’,6’-tetremethoxychalcone （1） was synthesized via the Claisen-Schmide condensation reaction between 2-hydroxy-4,6-dimethoxyacetoPhen-one and veratraldehyde. The semi-synthetic method for compound 1 with hesperidin as a starting compound was employed as well.2. Based on Mannich reaction with microwave assistant method or traditional relux method, aminomethyl groups at 3’-position was introduced to the compound 1 to afford Mannich base derivatives 1a-1g.3. With acetonitrile being solvent, aminoalkyl groups at the 2’-O-position was introduced to compound 2, and eight novel aminoalkyl-substituted polymethoxychal-cone derivatives 2a-2h was synthesized.4. Using the CCK-8 method, the antiproliferative activities of compounds 1, 1a-1g and 2a-2h against three human cancer cell lines （HeLa, HCC 1954 and SK-OV-3） were evaluated, with cis-Platin and Paclitaxel employed as positive controls. Except compounds 1 and le, other compounds expressd some inhibitor activity.The activities of compounds la, lc,2a-2g,2h against HeLa cell, 1a-1c & 2a-2h against HCC 1954, and 2b-2d against SK-OV-3 were more potential than cis-Platin.5.2-Hydroxy-3,4,5,6-tetramethoxyacetophenone （3） was total-synthesized with resorcinol as a starting compound after five-step reactions. Compound 3 was also collected by semi-synthsized by degradation of tangeretin with one step. A series of five novel polyoxymethchalcones compouds 3a-3e with active hydroxide group were synthesized via Claisen-Schmidt condensation between 3 and different benzaldehydes.6. In this thesis,15 nitrogen-containning polyoxymethchalcones and 5 new polyoxymethchalcones have been synthesized. All synthetic compounds above have been confirmed by more than one of the MS,1H NMR and 13C NMR and so on. |
