Research On Synthesis And Biological Activity Of Sugar-Ring Flourinated Analogs Of Digoxin

Fluorination is a commonly used modification method in modern medicinal chemistry and the introduction of fluorine atoms can change the lipophilicity,pKa value and metabolic stability of the molecules.Digoxin is a medium-acting cardiac glycoside drug.In recent years,it has been found that it also possesses good anticancer activity.In this dissertation,we describe the synthesis and application of sugar-ring fluorinated digoxin:This thesis optimized the synthetic route of fluorodigitoxose,and successfully prepared the sample on gram-scale;developed the synthesis strategy of fluorodigoxins with gold-catalyzed glycosylation as the key step.Starting from the fluorodigitoxose,six fluorinated digoxin analogs were successfully synthesized in 14 linear steps.The results show that the presence of fluorine atoms is beneficial for the construction of key?-glucosidic bonds.Biological tests showed that the fluorinated digoxin at the C2position of the three sugar rings had the best activity,with an IC₅₀ of 99 nanomolar for lung cancer cell A549.???This thesis will provide valuable information for the modification of natural products with fluorine,especially the synthesis and biological activity of fluoro-oligosaccharides.