Synthesis Of Baicalein Derivatives With Protective Effects Against The Liver Injury

Baicalein has strong protective effects on liver,and that has been proved by clinical application and pharmacological tests. So it will have good prospects in thefield of liver protecting agents to synthesize Baicalein and its derivatives.Although Baicalein has good liver protective effects,thek bioavailability is verylow because of its poor solubility. So we want to find some compounds which have high potency,low toxicity.We studied the SAR of Baicalein and other flavonoids,finding that the presence of free hydroxyl group at C-5 and C-7,the double bond between C-2 and C-3,the carboxide at C-4 and the2-phenyl group essential to keep their activities. On this base,we design the target molecules by modification of molecular structure of Baicaleinl.On the ring B of Baicalein,we use different substitutes such as halo,methoxy Imethylenedioxy,methyl et al to investigate their influence on liver protective effects.2.Remove the hydroxy group at C-6,and use above substitutes on the ring B of Baicalein to investigate the influence of hydroxy group at C-6 on the liver protective effects.According to above ideas,we design two routs to synthesize two series of title compounds respectively:1 .Phloroacetophenone reacts with an excess of an aroyl chloride in the biphase system under Tetrabuylammonium Bromide to get o-hydroxydibenzoylmethanes,Thenthey are cyclized by heating with aqueous 5% potassium carbonate followed bywe treatment with acetic acid. According above method we synthesized five compounds,theirstructures are confirmed by HNMR,MS,IR.2.Phloroacetophenone and substituted ethyl benzoylacetate are condensed under high temperature to get 6-acetyl-5,7-dihyoxyflavones,derivatives,Then by Baeyer-villager oxidation,they are transformedTrihydroxyflavone derivatives. We improved the synthesis method of substituted ethyl benzoylacete and get good results,But the condensation of phloroacetophenone with substituted ethyl benzoylacetate can't go on. It is possible because the acetyl group at phloroacetophenoene decreases its activity. The research of physiological activity of title compounds is in progress.