Ionic Liquid In The Liquid Phase Parallel Synthesis Of Natural Products Triterpenoid

Oleanolic acid(OA)(3β-hydroxy-olea-12-en-28-oic acid) is a triterpenoid distributed widely in nature.OA and its derivatives exhibited many kinds of bioactivities such as antitumor,anti-viral and anti-inflammatory activities,etc.To find novel anti-tumor compounds,the modification of OA is of particular interest.In the last decade,ionic liquids(IL) attracted significant and growing interests for their intrinsically useful properties such as high thermal and chemical stability,no measurable vapor pressure,and high loading capacity.IL is a perfect kind of green solvent.In which numerous chemical reactions can be carried out.Recently,some low weight ionic liquids have been used as soluble support for organic synthesis.The reaction was carried out in liquid phase,and its purification simplified by washing or extracting.So we began to explore the application of IL-supported modification of OA.We designed and synthesized the p-alkoxy benzyloxy moiety as the linker for conjugation of OA and IL,because the linker could be cleaved by weak acid treatment or hydrogenation.The functionalized ionic liquid 16 was prepared through seven steps which was linked to OA to furnish IL-supported OA(8) starting from the p-hydroxyl benzoic acid.Then C-3 hydroxyl of 8 was modified with acyl chlorides and cleaved to afford the desired products.The IL-supported compounds are well solved in highly polar organic solvent such as methanol and acetonitrile,and slightly solved in less polar organic solvent.They could be washed by ether or ethyl acetate for purification after reaction.Finally,the desired OA derivatives were obtained through the cleavage by acid hydrolysis or hydrogenation.Unfortunately the reaction that ionic liquid 8 linked to OA couldn't be purified by simple washing or extracting due to the poor solubility of OA in less poor organic solvent.So we designed another reaction route to overcome this problem.The linker was linked to OA firstly,then OA with linker reacted with functionalized ionic liquid to prepare compound 9.In fact,the compound 45 was tried to be prepared because of the stability of compound 9.We have also tried to prepare another type of IL-supported OA with ester-acetal linker which can be cleaved under milder acid in condition than the p-alkoxy benzyloxy cleavage.This route wasn't completed for the limited time.