Study On Synthesis And Activity Of Natural Product Peruviose D

Diabetes is a metabolic disease caused by insufficient insulin production or insulin dysfunction,and type Ⅱ diabetes is the most common form of diabetes.Common drugs used in the clinical treatment of type Ⅱ diabetes include biguanides,thiazolidinediones,sulfonylureas,and α-glycosidase inhibitors.Among these classes of drugs,in addition to the highly active α-glycosidase inhibitors,the most widely used clinically is Acarbose.Compared with drugs,Acarbose has higher safety in clinical use,but the corresponding indication selectivity is limited,so it is particularly important to seek a reliable α-glucosidase inhibitor.It was found that Peruviose D,a natural product based on sucrose as the basic skeleton,has a certain hypoglycemic effect.We conducted the first synthesis of Peruviose D and preliminarily tested its biological activity,which laid the foundation for the research of saccharose-based sugar drugs.The first chapter mainly summarizes the classification,etiology,and development trend of diabetes mellitus and diabetes II in recent years.In the second chapter,the development and synthesis of drugs for the treatment of type Ⅱ diabetes mellitus are reviewed,especially the synthesis of drugs.Besides biguanides,thiazolidinediones,sulfonylureas,and α-glycosidase inhibitors,this chapter also summarizes the research of some natural products with potential hypoglycemic activity,including flavonoids,terpenoids,and polyphenols.In the third chapter,using commercially available sucrose as the starting material,we differentiated the reactivity of the 8 hydroxyl groups of sucrose through a carefully designed orthogonal protection group strategy,and completed the first synthesis of Peruviose D in a longest linear 12 steps.Subsequently,α-glucosidase inhibitory activity was studied in Peruviose D and compared with Acarbose.We found that Peruviose D had no significant inhibitory activity against α-glucosidase,which needs further verification.The results of total synthesis and preliminary bioactivity test of Peruviose D in this thesis provide valuable experience for the future study of natural products with sucrose as the basic framework.