Highly Efficient Synthesis Of Bioactive Oleanane-type Saponins And The Development Of Copper-mediated Aryl-O-glycosylation

Carbohydrates play an important role in organisms,many of which have been used in the treatment of diseases.However,these endogenous are often present in low concentrations and micro-heterogeneous forms,making them extremely difficult to isolate and characterize.Therefore,chemical synthesis provides an important access.Saponins,complex glycosides of steroids or triterpenes,are widely distributed in plant kingdom and many of which have been claimed to possess a variety of bioactivities.Elatoside E,a typical oleanane-type saponin and isolated from the root cortex of Aralia elata Seem,is shown to lower the elevation of plasma glucose level.Its derivatives have also been shown to have different biological activities.The research work focused on the chemical synthesis of a group of structurally typical bioactive saponins isolated from plants.Firstly,we started with the economically available oleanolic acid and monosaccharides,leveraging on Schmidt glycosylation method.A highly efficient approach to obtain oleanane-type triterpene saponins was established.To further study its biological activity and structure-activity relationship,the cytotoxic activity of the obtained triterpenoid saponins was evaluated through bioactivity investigation,and the preliminary structure-activity relationship was deduced.This laid the foundation for exploring the relationship between the structure of sugar chains in saponins and their biological activities.Phenolic glycosides,a kind of the O-glycosides,generally have good biological activities and pharmacological effects.Over the past decades,chemists have developed a number of methods for the synthesis of phenolic glycosides.However,it still has several shortcomes,for example,the preparation of reactants is cumbersome and their properties are unstable,and the reaction would be accompanied by the formation of aryl-C-glycosides.Developing a highly efficient and convenient method for synthesizing phenolic glycosides has great significance.Herein,an efficient and novel methodology for phenolic glycoside has been established by using copper-mediated couplings of boronic acids with carbohydrates.The optional reaction conditions we selected:1.0 equiv.Cu（OAc）₂ as the promotor,reacting at 40 ^oC for 24 hours.This protocol has good substrate suitability and compatibility of protecting groups,which is appropriated for multifarious sugar substrates,such as glucose,galactose,mannose,fucose and so forth.Ayriad of phenolic glycosides could be synthesed in good yields.Furthermore,the formation of C-glycoside could be effectively avoided.