Studies On Synthesis Of Citrus Polymethoxyflavonoids And Flavonoid-glucoside Derivatives

Polymethoxyflavonoids (PMFs) are a class of natural products which widely exist in citrus plants. There has been increasing most concern from chemists and medicine chemists in the studies about PMFs due to their distinguished biological activities, including anticarcinogenic, antiviral, antiinflammatory, antioxidant, antithrombogenic, and anti-atherogenic properties. In order to further research the biologial activities of this class compounds and meet the need of new drug development, we would like to synthesize a series of polymethoxy flavonoids and flavonoid-glucoside derivatives.1. A key intermediate 2,3,4,6-tetramethoxyphenol (4) was synthesized from readily available material resorcinol through bromination, esterification and then nucleophilic substituent in high yields. We would like to synthesize pentamethoxybenzene (5), but to our surprise, the product was identified to be a demethyl compound (4), as the precursor of compound (5), which could be transformed to (5) by treatment with (CH3)2SO4 and K2CO3 in acetone. This is a new synthetic method for the preparation of 2,3,4,6-tetramethoxyphenol. We studied the reaction about synthesis of compound (4) and optimized the reaction condition. It should be mentioned it was an unexpected finding in the third step and it seems that we could never directly get the compound (5) in the third step throughout our experiment.2. A simple and feasible synthetic route was designed to synthesize a series of polymethoxy flavonoids. Compounds (6a) and (6b), which are the acetylation product of compound 5, reacted with various 3-, 4- or 5-methoxy substituted benzaldehydes (9a, 9b, 9c) and 1,4-Phthalaldehyde (14) to give polymethoxychalcones (10a, 10b, 10c, 12, 15). Then a series of polymethoxyflavonoids were synthesized by different cylization from the above chalcones. We improved a method to synthesize a group of hydroxylated polymethoxyflavonoids, which possibly pose some more strong bioactivities, with hydroxyl in 5-position by using Aluminum chloride/ether system in room temperature. This method has advantages of simple reagents, mild reaction conditions, easy separation of products and high yields.3. An important natural product 5,6,7,8,3′,4′-hexanemethoxyflavone-3-O-β- glucoside was first synthesized by an improved method from flavonol. In this work, the desired flavone-O-glucoside was synthesized from glucose by several steps including acetylation, bromization, glycosidation and deacetylation reaction. The synthetic procedure of glycosidation was modified by using anhydrous K₂CO₃ in acetone and TBBA as a phase transfer catalyst.4. All of the compounds have been confirmed by MS, IR, ¹H NMR and ¹³C NMR.