Synthesis Of 6-alkyl Substituted Purines And Their Nucleoside Derivatives Via Dehydrogenation Coupling Reaction

In view of the wide range of biological activities of 6-substituted purine derivatives in cancer treatment,antiplatelet aggregation and antiviral,there are more and more researches on 6-position modification of purine,including alkylation,arylation,amination and so on.Among them,6-alkylsubstituted purine and its nucleoside derivatives have a good application prospect in antiviral and cell activity inhibition.Therefore,it is very important to develop an efficient route for the synthesis of 6-alkyl substituted purines.This thesis focuses on the synthesis of 6-alkyl substituted purines and their nucleoside derivatives,and develops a green and mild technical route for the synthesis of 6-alkyl substituted purines and their nucleoside derivatives.The synthesis route is as follows:using 6-chloropurine as the starting material,9-substituted-6-chloropurine is obtained via alkylation at 9 position,and then a series of 6-hydropurine substrates are prepared by Pd/C reduction.After that,thirty 6-alkyl substituted purines and their nucleoside derivatives were successfully synthesized by dehydrogenation coupling reaction of oxalate with purine substrate under room temperature stirring and 12 W blue LED light induction with[Bis（trifluoroacetoxy）-iodo]benzene（PIFA）as oxidant.The structures of the products were confirmed by ¹H NMR,¹³C NMR and HRMS.This technique effectively overcomes the shortcomings of the traditional coupling reaction,such as the use of precious metal catalyst and the harsh reaction conditions,and can produce 6-alkyl substituted purine derivatives simply and efficiently.At the same time,the route has wide compatibility with carbonyl,ester,C=C,C≡C,cyano,benzyl and other functional groups.In addition,the first,second and third alkyl groups can achieve purine 6-position modification with high yield,and the highest yield can reach 94%.At the same time,the possible reaction mechanism was proposed based on the control experiment.It is worth noting that this technical route can be scaled up to gram scale.In conclusion,this paper has successfully explored a simple and efficient technical route for the synthesis of 6-alkyl substituted purine and their nucleoside derivatives,which provides technical support for the development of new purine active molecules.