Synthesis Of C2and C6Modified Purine Nucleoside Derivatives

A large number of modified nucleoside derivatives demonstrated variousanti-tumor, antiviral and other biological activity, and a number of new drugs havebeen approved for clinical studies or treatment HCV, HIV, HBV, anticancer and othercritical diseases. Purine nucleoside derivatives represent an important class ofbiologically active compounds that have been extensively explored for their antiviral,antitumor, and other properties,such as:6-Substituted purine nucleoside derivativeshave been studied and exhibited potent biological activity;The purine ribonucleosideshaving aryl or heterocyclic substituents in position6exhibit cytostatic activitiesagainst various tumer cell-lines;Moreover,some6-heterocyclic substituted purineribonucleosides also exert strong antiviral activities.2’-beta-C-methyl-6-substitutedpurine nucleosides exhibits very promising anti-HCV activity by targeting RNAdependent RNA polymerase.Synthesis,biochemical activity assay and drug choosingof novel purine nucleoside and nucleoside derivatives are becoming the researchfocus recently.First of all, we got the needed purine nucleoside intermediates directly by theclassical glycosidation reaction from two different protected ribose and a variety ofpurine bases, and then we designed three routes according to the substituents on thebases:(1)We got the amino-substituted purine derivatives by a simple and rapidmethod,that amination and deprotection could react in one step;(2)We got thehydrogenated product under Pd/C from chlorinated intermediates,and the finalcompound was obtained with further deportected;(3) By the classical SuzukiCoupling or Stille Coupling reaction to react with a heterocyclic boronic acid or anorganotin reagent,finally we synthesized a series of heterocyclic or aryl groupsubstituted purine nucleoside.In the end,we got two different series of purinenucleoside derivatives.In addition, we also done some work on the amination of6-chloropurinenucleoside and2-amino-6-chloro purine nucleoside,that enriched the types ofnucleosides,we also tested the biological activity of the compound. Meanwhile,some research work was done about the synthesis of Iso guanosine. Despite various studies of modified purine nucleosides, there is still a need for thedesign of new analogues and development of novel nucleoside-based therapeutics. Inparticular, there is a need for new therapies for the treatment of drug-resistant tumorsand viruses.