Stereoselective Synthesis of Novel Isonucleoside Analogues of Purine with a Tetrahydropyran Ring

摘要

New tetrahydropyran isonucleoside derivatives of purine, with cis or trans configuration, were stereoselectively synthesized in moderate yield by a convergent strategy based on Mitsunobu coupling. The key starting material was a bicyclic lac-tone.Nucleoside analogues play an important role in chemotherapy.1 Modifications in the sugar moiety of nucleosides have led to the development of novel derivatives, including acyclic and carbocyclic nucleosides, four- or six-membered ring analogues, 2',3'-dideoxynucleosides, and isonucleosides, that have shown interesting antiviral and anticancer properties.2 These modifications are often associated with increased stability2 and decreased toxici-ty,3 together with target specificity.2 In isonucleosides the heterocyclic base is linked to the non-anomeric carbon atom of the sugar moiety, in particular at C2' or C3' of the furanose ring. The change in the position of the sugar-base bond keeps the spatial placement between the base and the 5'-hydroxy group, while the glycosidic bond is more stable toward enzymatic hydrolysis. Several isonucleosides show interesting biological activity.