Studies On Chemical Transformation Of Hesperidin And Synthesis Of New Flavonoids And Their Biological Activities

Flavonoids comprise a large group of naturally occurring,low molecular weight, polyphenolic compounds widely distributed in the plant kingdom as secondary metabo- lites.They represent one of the most important and interesting classes of biologically active compounds and occur both in the free state and as glycosides. Both hesperidin and its aglycone hesperetin which are mainly contained in Citrus cultivation as an abundant and inexpensive by-product have been reported to possess a wide range of pharmacological properties, including antivascular-disease activity, antiinfective and antifertility activity, anticarcinogenic activity, antiviral activity, antioxidant effect.In order to meet the needs for studying on synthesis method and select the substances with biological activities. This thesis aims at the studies on the semisynthesis of a series of new flavonoids from hesperidin and synthesis of four new flavonoids and their bioactivity.1.four key intermediates, hesperetin, methylhesperetin, methylhesperetin chalcone and diosmetin, were synthesized from hesperidin, through hydrolyzation, methyl- lation, Ring-Opening reaction, dehydrogenation. These four compounds reacted with trans, trans-farnesyl bromide or prenyl bromide, synthesized eight new flavonoids, including 1c, 1d, 1e, 1f, 1g, 2b, 2c, 3b.2.Synthetic routes of flavonoids derivatives were proposed. On the basis of the designation, which chalcones act as the key intermediates and 3,5-dihydroxybenzoic acid acts as a raw material, a series of new flavonoids were synthesized, including 5a, 5b, 6a, 6b, 6c, 7a, 7b, 7c, 7d, through esterification, etherification, oxidation, deoxidization, aldol condensation.3.The biological activities of the new flavonoids were tested, using two international standard model MMP-9 (anti-osteoporosis) and CCLT (anti-cancer). Results showed that four compounds have inhibition activity. 7b has inhibition of MMP-9 and 6c, 7b, 7c, 7d has inhibition of CCLT [6c for SGC-7901 (gastric cancer cell line); 7b for BGC-83 (gastric cancer cell line);7c for MDA-MB-231 (breast cancer cell line); 7b, 7c, 7d for U251 (human glioma cell line); 7b, 7d for B16 (murine melanoma cell line)].4.All of the compounds have been confirmed by MS, IR, ¹H NMR and ¹³C NMR.