天然5,7-二羟基-3-异戊烯基黄酮与5-羟基-3-异戊烯基黄酮的全合成

以2,4,6-三羟基苯乙酮和2,6-二羟基苯乙酮为原料, 分别通过甲基保护酚羟基、 苯甲酰氯酰化、 Bake-Venkataraman重排、 异戊烯基化、 酸催化关环及EtSLi脱去甲基等6步反应, 以高收率完成了天然5,7-二羟基-3-异戊烯基黄酮(1a, 收率80.6%)和5-羟基-3-异戊烯基黄酮(1b, 收率84.9%)的全合成, 所有化合物均经 ¹H NMR 和 ¹³C NMR表征确定. 通过密度泛函理论方法对目标产物(1a和1b)的生物活性进行了预测. 结果表明, 3位异戊烯基侧链的存在能大大增强化合物相应的生物活性, 而且是化合物生物活性增强必需的取代基. 另外, 目标产物1a的生物活性高于产物1b, 归因于黄酮类化合物分子中A环上的7-OH属增效基团, 起到增强生物活性的作用, 化合物1a分子中A环上有7-OH, 而化合物1b分子中则无该基团. 本合成方法对其它3-烃基黄酮类天然化合物的合成具有潜在的适用性, 所预测的生物活性结果为3-烃基黄酮类化合物的构效关系研究奠定了基础.

Total Syntheses of 5,7-Dihydroxy-3-isopentenylflavone and 5-Hydroxy-3-isopentenylflavone Natural Compounds

The total syntheses for 5,7-dihydroxy-3-isopentenylflavone(1a,yield 80.6%) and 5-hydroxy-3-isopentenylflavone(1b,yield 84.9%) were performed through selective protection of phenolic hydroxyl groups,acylation,Bake-Venkataraman rearrangement,prenylation,cyclization and demethylation,which started from 2,4,6-trihydroxyacetophenone and 2,6-dihydroxyacetophenone,respectively.The structures of all the compounds were characterized by 1H NMR and 13C NMR,and the biological activities of the target compounds(1a and 1b)were predicted by the density functional theory(DFT) calculations.The results showed that the isopentenyl substituent at C3 could remarkably improve the biological activities of the flavonoids,and it was requirement for various biological activities of the flavonoids.In addition,the biological activities were 5,7-dihydroxy-3-isopentenylflavone(1a)>5-hydroxy-3-isopentenylflavone(1b).The reason might lie in the fact that the 7-OH of the flavonoids could enhance the biological activities.The synthetic routes in the present work might reveal potential applicability in the total syntheses of other 3-alkylfavones natural compounds and the biological activities of the target compounds could lay a good foundation on studying the structure-activity relationship of 3-alkylfavones.