The Synthesis Of (E)-7,8-pyran Isoprenyl-3- Benzylidene-hesperidin Derivatives And Study On Anti-Tumor Activity

Flavonoids are common compounds in nature.They are abundant in variety and content.They are important components of natural medicines.Their extraction and preparation process is simple and cheap.Flavonoids have a wide range of pharmacological activities and broad medical application prospects.Flavonoids are synthesized by green plants,which mainly play antioxidant,antimicrobial,antiviral and anti-inflammatory effects in plants,and are used to protect plants.Because natural flavonoids are secondary metabolites of plant enzymes,they mostly contain phenolic hydroxyl groups.Due to the uneven distribution of phenolic hydroxyl groups,catechol OH was not formed and its antioxidant activity was weak.And the water solubility of flavonoids is low,which leads to the low bioavailability of flavonoid glycosides.The content of the paper is divided into three sections:1.Hesperidin and naringin,which are rich in natural resources,simple in extraction process and low in price,are used as raw materials.By adding 3-methylene-phenyl derivatives,the number of rings and phenol OH,-OCH₃ and amino groups can be increased.The conjugation of phenol OH,-OCH₃ and amino groups can be greatly expanded.Lipid-water partition coefficient is easy to adjust.A colorful E-3-?phenyl derivative-methylene?-pyran dihydroflavone derivative can be obtained.2.Using 8,8-dimethylpyran-hesperidin as substrate,organic base+organic acid as catalyst in polar solvent,benzaldehyde derivatives were synthesized by aldol condensation reaction.The mol ratio of pyran?7,8?-dihydroflavone to benzaldehyde derivatives was 3:1-1:3.The reaction temperature was controlled at room temperature-100 C,and the reaction time was controlled for 1h-72h.A novel pyran isoprenyl flavone derivative was synthesized and characterized by¹H-NMR,¹³C-NMR and HRMS.3.A series of new?E?-7,8-pyran isoprenyl-3-benzylidenyl-hesperidin derivatives?HP-1-HP-14?were tested for their antineoplastic activity.The inhibitory effects on human lung cancer cells?A549?,human hepatoblastoma?HEPG2?,proliferating epidermal cancer cells?HELA?and human breast cancer cells?MCF-7?were studied,which laid a foundation for the development of new antineoplastic drugs.The results showed that the water solubility,alcohol solubility and antioxidant activity of the newly synthesized?E?-7,8-pyran isoprenyl-3-benzylidene-hesperidin derivatives were increased.Twelve new compounds?HP1-10,HP13-14?have stronger antitumor activity than hesperetin and hesperidin.It has more advantages,broad clinical application prospects and potential economic and social benefits.