Study On The Synthesis Of Saikosaponins

Saikosaponin A and D were isolated from the traditional Chinese medicinal material Bupleurum Saikos by Shibata Group of Tokyo University in 1965.Studies have shown that Saikosaponin A and D have anti cancer and antidepressant physiological activities.Structurally,saikosaponins A and D have a unique pentacyclic triterpenoid(PT)aglycon structure and a 3-O-(β-D-glucopyranosyl)-β-D-fucosypyranoside fragment at the C3 position,which pose a certain degree of difficulties in the chemical synthesis.In the synthesis of sugar fragments,we used selective glycosylation to efficiently construct a disaccharide backbone,and obtained.glycosylated donors with a satisfactory yield of 53%in 7 steps.For the synthesis of the aglycon part,we took the commercially available raw material oleanolic acid as the starting material,and employed a chiral amine as the directing group to successfully introduce C16-OH of oleanolic acid;then,we used intramolecular nucleophilic substitution reaction to construct 13,28-epoxy-ether moiety;afterwards,oxime was used as the directing group to functionalize the 23 position of oleanolic acid to realize the introduction of key hydroxyl groups.The synthesis of aglycone was achieved with a yield of 11%in 20 steps.Finally,the key glycosidic bond was constructed by the method of gold-catalyzed glycosylation,furnishing the first total synthesis of saikosaponin A.Although there is only one subtle structural variation between saikosaponin A and D,it is difficult to synthesize saikosaponin D according to the strategy of saikosaponin A due to the chirality of the triterpene C16-OH.Considering that the substrate is vulnerable to acidic conditions,we first construct the glycosidic bond,and then reverse the configuration of the triterpene C16-OH.After introducing the C16-one and C23-OH according to the similar method,the synthesis of PT aglycone was completed in 23 steps with a yield of 8.5%.By employing the gold-catalyzed glycosylation method,the required β-glycosidic bonds was constructed.Finally,the synthesis of saikosaponin D was completed through reduction and deprotection operations.Under similar conditions as the synthesis of saikosaponins A and D,we synthesize other congeners.By adjusting the sugar fragments,the method of gold-catalyzed glycosylation was successfully applied to synthesize saikosaponin,Saikogenin Y and Clinposaponin Ⅰ.