单甲基化表没食子儿茶素没食子酸酯的化学合成

The Chemical Synthesis of Monomethylated Epigallocatechin Gallate

表没食子儿茶素没食子酸酯(EGCG)经甲基化后在抗过敏、降血脂等方面具有更高的生物活性。但茶叶中甲基化EGCG含量较低,为进一步研究其生物活性,本文对其半合成路线进行了优化。先以EGCG为原料制得五苄基化的表没食子儿茶素(EGC),然后将没食子酸丙酯经4-甲氧基苯甲醛二甲缩醛保护,甲基化,脱保护,苄基化,水解得到3,4-二苄氧基-5-甲氧基苯甲酸,再与苄基化EGC酯化和脱苄基得到表没食子儿茶素3-O-甲基没食子酸酯(3″-Me-EGCG);同样将没食子酸丙酯经全乙酰化、选择性甲基化、脱除乙酰基、苄基化、水解得到3,5-二苄氧基-4-甲氧基苯甲酸,再与苄基化EGC酯化和脱苄基得到表没食子儿茶素4-O-甲基没食子酸酯(4″-Me-EGCG);总产率分别为53%和57%。

(-)-Epigallocatechin 3-O-methyl gallate(3″-Me-EGCG)and(-)-epigallocatechin 4-O-methyl gallate(4″-Me-EGCG),minor natural compounds of green tea polyphenol,exihibit antiallergic and hypolipidemic activity.In this study,semisynthetic methods of 3″-Me-EGCG and 4″-Me-EGCG were modifidied to investigate their biological activity.The key intermedite pentabenzylated epi gallocatechin(EGC)was prepared by benzylation of epigallocatechin gallate(EGCG)and hydrolysis of perbenzylated EGCG.Protection of propyl gallate by 4-methoxybenzaldehyde dimethyl acetal with subsequent methylation,deprotection,benzylation,and hydrolysis produced 3,4-bis(benzyloxy)-5-methoxybenzoic acid.This acid was then reacted with pentabenzylated EGC to afford an ester which was debenzylated to provide 3″-Me-EGCG;Acetylation of propyl gallate with subsequent selective methylation,removal of acetyl,benzylation,and hydrolysis gave 3,5-bis(benzyloxy)-4-methoxybenzoic acid,which was reacted with penbenzylated EGC to get another ester which was debenzylated to obtain 4″-Me-EGCG.The total yields of 3″-Me-EGCG and 4″-Me-EGCG were 53%and 57%,respectively.