Synthesis Of 2’-dA Derivatives

With the gradual deepening of deoxyadenosine research,it has been found that the modification of different positions on the skeleton can exhibit various medicinal activities.For example,the 2-position modified substrates has anti-hairy leukemia activity,and the modification on 6-position can treat Kawasaki disease,deoxyribose partially modified derivatives have performed well in the treatment of AIDS.Based on the huge potential application of modified deoxyadenosine and the deficiency of traditional synthetic methods,this paper focuses on the modification of 6-position,8-position and 5’-position of deoxyadenosine.Firstly,modification on 6-position of2’-deoxyadenosine,2’-deoxyadenosine is used as the starting material to achieve Cu（I）-catalyzed via Buchwald-Hartwig reaction,and the 6-position C-N bond is constructed in one step.Compared with the traditional Pd-catalytic synthesis method,the method does not require additional steps such as protection and deprotection,and the route is simpler,reaction conditions are mild with high the functional group compatibility.Thirteen N⁶-arylamino-2’-deoxyadenosine are synthesised and the structures of title compounds are confirmed by IR,¹H NMR and ¹³C NMR.Secondly,modification on 8-position of 2’-deoxyadenosine,using 2’-deoxyadeno-sine as the starting material.After 8-position halogenation and nucleophilic substitution reaction,8-substituted derivatives are obtained,and we will discusse the further research of double-substituted synthetic route at 6-position and 8-position.According to the 2’-deoxyadenosine modification method,2’-deoxycytidine is also modified to obtain2’-deoxycytidine derivatives.Finally,the research of 2’-deoxyribose-5’-hydroxyphosphorylation modification,with 2’-deoxyadenosine as the starting material.Firstly reacted with phosphorus oxychloride to synthesize dAMP,tributylammonium salt of dATP is obtained by tributylammonium pyrophosphate.High-purity dATP sodium salt can be obtained by ion-exchanged with 0-1 mol/L tetraethylammonium bromide eluent and ion exchange with sodium perchlorate in acetone to remove the solvent.Compared with the traditional method,the method is more concise,the yield is higher,the ion exchange purification method is simpler,and a more efficient synthetic route is provided for the industrialization of dATP.The same method also effectively synthesizes dCTP and dTTP.The derivatives is characterized by IR,¹H NMR,¹³C NMR and ³¹P NMR.This thesis explores new synthetic methods or improves traditional synthetic methods,and prepares a series of novel 2’-deoxyadenosine derivative molecules to provide technical reference for the synthesis of novel anti-tumor and anti-viral deoxyadenosine derivatives.