目的设计并合成白藜芦醇的多种糖苷衍生物,测定其与全反式维甲酸(ATRA)联合用药后对人类急性早幼粒细胞白血病细胞株(MB4)的诱导分化作用。方法应用保护基策略,采用Schmidt成苷法制得目标产物;采用NBT还原法测定细胞分化百分率。结果与结论合成了10个白藜芦醇的单糖苷化衍生物,其中,Res-3-Rha、Res-4′-Rha、Res-4′-Xyl、Res-4′-Ara是未见文献报道的新化合物;Res-3-Xyl和Res-3-Ara为首次合成的化合物,其结构均经核磁共振氢谱和质谱确证。自藜芦醇及其10个糖苷衍生物与ATRA的联合给药初筛结果表明,Res-3-Glc、Res-3-Ara、Res-3-Rha、Res-4′Glc、Res-4′-Ara、Res-4′-Xyl及5μmol·L^-1的白藜芦醇和Res-4′-Rha均能明显提高ATRA的诱导细胞分化活性。
Aim To find novel resveratrol glycosides with differentiation effects of NB4 cells after combining administration with all-trans retinoic acid (ATRA). Methods The target compounds were synthesized by Schmidt's glycosidation method, and were screened by NBT reduction assay. Results and conclusion Ten resveratrol glycoside derivatives were synthesized, including four new compounds Res-3-Rha, Res-4′-Rha, Res-4′-Xyl, Res-4′-Ara and two firstly synthesized compounds Res-3-Xyl and Res-3-Ara, and their structures were identified by ^1H-NMR and ESI-MS. The differentiation rates of groups treated with combination of ATRA with Res-3-Glc, Res-4′-Glc, Res-4′-Xyl, Res-3-Ara, Res-4′-Ara, Res-3-Rha at the concentration of 5 μmol· L^ - 1 and 10μmol· L^- 1, and resveratrol, Res-4′-Rha at the concentration of 5 μmnol· L^ -1 were significantly higher than those treated with the same dose of ATRA alone.