Chemical synthesis, hydrolytic stability, and biological evaluation of 4’-thionucleosides and their analogs

Synthesis of 4’-thionucleosides and their analogs (2’-Modified 4’-thionucleosides, 6-Azapyrimidine-2’-deoxy-4’-thionucleosides, 4’-Ethynyl-2’-deoxy-4’-thionucleosides, 5-Substituted 2’-Deoxy-2’-fluoro-4’-thionucleosides)has been discussed briefly in this review. Hydrolytic stability of purine and cytosine 2’-deoxy-4’-thionucleosidesand 2’-deoxy-4’-thiouridines and their 5-substituted analogs in aqueous acidic solutions was also elaborated. This study shows that cytosine and purine 2’-deoxy-4’-thionucleosides are more stable toward acidic hydrolysis than their unmodified counterparts. The reactivity ration ranges from 40 to 70 with purine thionucleosides and about 7 with cytosine thionucleosides. No other nucleosidic products or intermediates have been accumulating during the hydrolysis and the above mentioned thionucleosides. The N-glycosidic linkages of the 2’-deoxy-4’-thiouridines and their 5-substituted analogs are also more than one order of magnitude more stable toward acidic hydrolysis than are those of their native counterparts. A series of 4’thionucleosides has been evaluated for antitumor and antiviral activities.