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为了立体选择性合成全甲基化没食子儿茶素没食子酸酯(GCG),本文以全甲基化表没食子儿茶素没食子酸酯(EGCG)为原料,通过酯水解和Mitsunobu反应立体选择性地合成了构型C-3位翻转的目标产物全甲基化GCG。全甲基化GCG经水解得到5,7,3′,4′,5′-五氧甲基没食子儿茶素(GC),再经Mitsunobu反应得到全甲基化EGCG。经核磁和旋光验证,所合成的全甲基化EGCG与原料全甲基化EGCG相同。核磁测试证实两次Mitsunobu反应产物C-3均发生立体构型翻转。初步细胞实验表明1μmol/L全甲基化GCG与紫杉醇共同作用于P-gp高表达LCC6/MDR乳腺癌耐药细胞株时,紫杉醇IC50为10.1nmol/L,全甲基化GCG逆转倍数(RF)达到13.9。
In order to stereoselectively synthesize full-GCG, GCG was prepared by using the fully methylated epigallocatechin-3-gallate (EGCG) as a starting material through stereoselective esterification and Mitsunobu reaction The target product of methylated GCG was synthesized. The fully methylated GCG is hydrolyzed to give 5,7,3 ’, 4’, 5’-pentoxymethyl gallate (GC), followed by Mitsunobu reaction to obtain fully methylated EGCG. The results of NMR and polarimetry show that the synthesized methylated EGCG is the same as the original methylated EGCG. Nuclear magnetic test confirmed that both Mitsunobu reaction products C-3 stereotypes flip. Preliminary cell experiments showed that paclitaxel IC50was10.1nmol / L, the methylation GCG reversal fold (RF) was10|Ìmol / L when the methylated GCG and paclitaxel combined with P-gp overexpressing LCC6 / MDR breast cancer cell lines ) Reached 13.9.