Synthesis And Bioactivity Of Fluorinated Derivatives Of Swainsonine And Digoxin

Fluorination has become one of the most used methods of drug research and development,and the products after structural modification often have better or different biological activities.This dissertation consists of two sections.1?The synthesis of Swainsonine and its fluorinated derivatives Swainsonine,isolated from Swainsona canescens,is a potent inhibitor of Golgi mannosidase II and may be useful in the treatment of cancer and other diseases.In this dissertation,compound 148a was used as the key synthon,in the syntheses of swainsonine,its epimer and their corresponding enantiomers,with Barbier reaction,borohydride oxidation and reductive amination as key steps.Based on the successful synthesis of swainsonine,two fluorinated derivatives of the natural product were also synthesized,which laid a good foundation for the development of follow-up fluorinated derivatization of swainsonine.2?Synthesis and activity of 2-fluoro-2,6-dideoxy sugar and fluorinated digoxin Fluorinated compounds comprise a substantial proportion in the therapeutic drugs.Introduction of fluorine or fluorinated substitutes is also an important strategy in structure-modification of bioactive small molecules.In recent years,the research of fluorinated sugar has attracted much attention.In this work,the synthetic method of 2-fluoro-2,6-dideoxy sugar was studied,which promoted the successful fulfillment of 2-fluorodigitalis and 2-fluorocymarose.Based on the strategy research,the synthesis of fluorodigoxin was also completed.Subsequent biological activity assay showed that the fluorinated products exihibited nearly ten times lower inhibition on A549cells than that of digoxin.This may be attributed to the hinderance of fluorine in the binding of the drug to the target,which has some refererence value for the subsequent fluorination work of other sugar ring units of digoxin.