Synthesis Of 2-alkylthio-N~6-arylpurine Nucleosides/6-arylpurines

Many purine-containing molecules were found to have excellent antiviral,antibacterial,inhibitory cell growth,regulation of the immune system and antithrombotic effects.Therefore,it is of consistent interest for pharmacologists and chemists to modify the structure of adenosines,to study their bioactivities and to develop its application on being drug.On the basis of this,the paper reports the modification of purine molecules with:1.Synthesis of 2-alkylthio-N6-arylpurine derivatives2-Alkylthio-N6-arylpurine derivatives were synthesized from commercially available guanosine through acetyl protection of glycyclic hydroxyl,chlorination of hydroxyl group at the 6-position,diazotization-alkylthionation at the 2-position,nucleophilic substitution with various substituted anilines at the 6-position and deacetylation process.Meanwhile,the mechanism of diazotization-alkylthionation was investigated and a proposed mechanism was provided.Buchwald-Hartwig amination reaction was used to obtain the adenosine derivatives with strong electron-withdrawing anilines to circumvent the unreacted nucleophilic substitution of weak nucleophilic aromatic amines to 6-halopuines.Finally,21 compounds of 2-alkylthio-N6-arylpurine derivatives were synthesized and characterized,part of which antiplatelet aggregation activities were also investigated.The antiplatelet aggregation results indicated that both anticoagulant activities of ADP and AA-induced platelet aggregation were inefficient.Compared with the BF061,these compounds,containing less carbon on their 6-amino alkyl chain,provided inferior anticoagulant activity.Moreover,the length chain of 2-alkylthio substitution on adenosine also did not have obvious activity on antiplatelet aggregation.2.Synthesis of 6-aryipurinesAn economical,efficient and mild method for the selective arylation of purine at the 6-position with aryl boronic acid as an arylation agent was developed.This approach used inexpensive silver nitrate as catalyst and ammonium persulfate as oxidant.The experiments were carried out under the ambient environment without the use of transition metal and inert gas,verifying that the method not only had a wide scope of substrates and functional group compatibility,but also could be scaled up.During the arylation,the addition of TFA not only accelerated the reaction but also promoted the regioselectivity.Moreover,this process could be utilized to synthesize mycobacterium tuberculosis inhibitor 6-(4-methoxy)phenyl-adenosine.A possible mechanism of this transformation was provided according to the experiments and NMR characterization.Finally,27 target molecules were successfully synthesized and characterized.