Studies On Glycosylation Of 3,5-trans-3-Amino-2,3,6-trideoxyhexopyranoses

3-Amino-and 3-nitro-2,3,6-trideoxypranoses are a class of structural diversified of rare sugars,which are widespread around bioactive natural products and drugs.As components of glycoconjugates,these scaffolds play essential roles in the activity of the biologically important natural products and therapeutic agents.Thus,modifications of the carbohydrate moiety of these compounds often lead to significant changes in activity,these findings provide a new approach to the discovery of more active compounds.However,there have been two obstacles that hampered the discovery of aminosugar-containing drugs.First,the synthesis of 3-aminosugar monomers is a daunting task.Second,their glycosylation is extremely challenging.Therefore,based on our recently developed diversity-oriented synthetic strategy of 3-aminosugar monomers,further exploration of their glycosylation,assembly in oligosaccharides and application in drug modifications has important significance in development of new drugs.This thesis first explored the synthesis of disaccharide and trisaccharide fragment of Saccharomicins A,B and investigated the couplings of 3-aminosugar by Interrupted Pummerer reaction mediated glycosylation developed by our group.By installing strongly electron-withdrawing protecting group to 3-aminosugars we prepared various 3-amino glycosyl donors.Further,subjecting these donors to classical activation conditions,we examined their glycosylation efficiency and stereoselectivity.These studies led to the effective synthesis of a pair of tetrasaccharides containing four different 3-aminosugar components either α or β linkages.On the basis of these studies,we further applied 3-aminosugars to the modifications of digitoxin and digoxin.The couplings of 3-aminosugar donors with steroidal aglycones were effectively realized based on Yu glycosylation.Then two-step deprotection successfully offered different types of 3-aminosugar analogues of digitoxin and digoxin.This strategy paved the way for examination of their anticancer activities as well as the SAR studies.In conclusion,this study has guiding significance for the synthesis and modification of complex natural products and drugs containing 3-aminosugars.