Studies On The Synthesis Of Polymethoxy Flavonoids Hydroxyethylated And Aminoalkylated Derivatives

Flavonoids are widely found in nature and have pharmacological activities such as anti-oxidation,antibacterial,anti-allergic,hemostatic,anti-pyretic?and cardiovascular and cerebrovascular protection.However,due to their poor water solubility and low bioavailability,their structures need to be modified to increase activity.Hydroxyethylation is not only increases solubility,but also improves chemical stability.Through the Hofmann alkylation reaction,a nitrogen atom-containing group can be introduced on the basis of the original compound.This nitrogen-containing group belongs to the active group in medicine,and many flavonoid drugs contain nitrogen-containing groups,not only can increase the water solubility of flavonoids,but also greatly improve its pharmacological activity.Many flavonoids contain nitrogen-containing groups,which can effectively improve the pharmacology of activity and solubility.This paper synthesized a series of hydroxyethylated and aminoalkylated polymethoxy flavones derivatives by using tangerine and nobiletin from polymethoxy flavonoids as starting materials.1?Natural product 3-hydroxytangerine and 3-hydroxynobiletin were synthesized through DMDO oxidation,using tangerine and nobiletin as raw materials,which are abundant in yield,very easy to get and inexpensive polymethoxylated flavonoid compounds.Compounds 3-hydroxyethoxy-4',5,6,7,8-pentamethoxyflavone(1)and 3-hydroxyethoxy-3',4',5,6,7,8-hexamethoxyflavone(2)were synthesized through hydroxyethylation of the phenolic hydroxyl groups,using 3-hydroxytangerine and 3-hydroxynobiletin as raw materials.2?Natural product 5-hydroxytangerine and 5-hydroxynobiletin were synthesized by 5-demethylation using tangerine and nobiletin as raw materials,which are abundant in yield,very easy to obtain,and inexpensive polymethoxylated flavonoids.5-(2-bromoethoxy)-4',6,7,8-tetramethoxyflavone(3)was synthesized through 5-hydroxytangerine with 1,2-dibromoethane occurred substitution reaction.Also,5-(2-bromoethoxy)-3',4',6,7,8-pentamethoxyflavone(4)was synthesized through 5-hydroxynobiletin with 1,2-dibromoethane occurred substitution reaction.3?A series of aminoalkylated polymethoxy flavones derivatives 3a?3h were synthesized through Hofmann alkylation reaction of secondary amines by using compound 3 as the substrati on.And,a series of aminoalkylated polymethoxy flavones derivatives 4a-4h were synthesized through Hofmann alkylation reaction of secondary amines by using compound 4 as the substration.4?Eighteen hydroxyethylated and aminoalkylated polymethoxy flavones derivatives were synthesized in this paper,they are all new compounds that have not been reported in the literature.The structure of the synthesized compounds have been confirmed by1H NMR,13C NMR and MS techniques.