β-榄香烯含S, Se糖苷衍生物的设计合成

以β-榄香烯(1)为先导化合物, 经由其13位氯代物(2), 依据生物电子等排原理将具有相似共价半径的杂原子S和Se分别引入到β-榄香烯的骨架中, 得到一对相应的类似物3和6; 进而通过多种方法与系列糖供体对接, 立体选择性地合成了相应的乙酰化1,2-反式糖苷类衍生物11a~11c和12a~12c, 经水解脱去保护基团, 得到目标产物β-榄香烯含S糖苷13a~13c及其类似物β-榄香烯含Se糖苷14a~14c. 目标化合物的结构经IR, 1H NMR, 13C NMR, 77Se NMR, HRMS等方法确证.

Design and Synthesis of β-Elemene Glycoside Derivatives Containing Heteratom S or Se

For the purpose of hunting for better water solubility and anti-tumor activity derivatives, structural modification of anticancer agent β-elemene was reported. Significant heteroatom S and Se were introduced into the skeleton of β-elemene and a pair of bioisosteres 3, 6 were obtained. Whereafter, conjugation with a series of glycosyls selectively gave the corresponding 1,2-trans-glycosides 11a—11c, 12a—12c via several approaches. Then target compounds 13a—13c, 14a—14c were obtained in high yields after deprotection. Heteroatom Se and hydrophilic saccharides were introduced into the skeleton of β-elemene for the first time, and a convenient method was set up for the synthesis of selenide of β-elemene. The glycosylation results demonstrate that glycosyl trichloroacetimidate was a suitable donor for the glycoside synthesis of β-elemene. The structures of products were confirmed via IR, 1H NMR, 13C NMR, 77Se NMR and HRMS spectra.