Selective Construction Of Fructofuranose Glycosidic Bonds Through Side-chain Neighboring Group Participation

Vaccine is important in prevention of infectious diseases and disease treatment.The traditional vaccines are mainly obtained by inactivation or attenuation of pathogenic microorganisms.However,there are disadvantages of insufficient safety since they are derived from pathogenic microorganisms.The chemically assembled vaccine contains clear and controllable components and is safer and more reliable.However,artificially prepared antigens usually do not cause strong enough immune response.The vaccine particles thus needed to be engineered to effectively increase their immunological activity.Currently,the modification of vaccine particles mainly relies on adjuvant,but synthetic vaccine-adjuvant system is still difficult to induce high-efficiency,long-term immune response and thus provide reliable protection,so its effectiveness urgently needs to be improved.Inulin is a relatively effective vaccine adjuvant.It is high biocompatible,non-toxic and stable in the human body,but can be metabolized by the intestinal flora.Inulin could also bind to TLR2 to boost the immune response.These properties make Inulin a good adjuvant.Therefore,we choose short chain Inulin,oligo-?-(2,1)-fructoside,as a component to prepare new artificial vaccines.However,synthesis of enough ?-linked oligofructoside is still a challenge through existing method and related immunological research only has limited progress.The construction of ?-linked fructofuranoside is a major problem in glycochemistry.For the first time,we employed 1-O-acetate of fructoside to control the anomeric configuration,and we found the conformation of five-membered furan ring is important in the glycosylation.Selective glycosylation is achieved from pseudoequatorial conformation of the fructose intermediate.We synthesized 1-O-acetyl-3,4,6-tri-O-benzyl-thiofructofuranoside as a donor and obtained promising a selectivity,which meets our predictions of neighboring group participation model.Therefore,we next attempted to synthesize a fructose donor with 3,6-lactone,a structure with pseudodiaxial conformation.After several attempts,this work is underway.