Synthesis of 5,7‐disubstituted‐4‐β‐D‐ribofuranosylpyrazolo[4,3‐d]‐pyrimidines and 2,4‐disubstituted‐1‐β‐D‐ribofuranosylpyrrolo[3,2‐d]‐pyrimidines as congeners of uridine and cytidine

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The synthesis of the congeners of uridine and cytidine in the pyrazolo[4,3‐d]pyrimidine and pyrrolo[3,2‐d]‐pyrimidine ring system is described. Glycosylation of the trimethylsilyl (TMS) derivative of pyrazolo[4,3‐d)pyrimidine‐5,7(1H,4H,6H)‐dione (4) with either 1‐bromo‐ or 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐D‐ribofuranose 5 and 6, respectively in the presence of a Lewis acid catalyst gave the protected nucleoside 7, which on debenzoylation afforded the uridine analogue 4‐β‐D‐ribofuranosylpyrazolo[4,3‐d]pyrimidine‐5,7(1H,6H)‐dione (8). Thiation of 7 gave 13, which on deprotection yielded 4‐β‐D‐ribofuranosyl‐5‐oxopyrazolo[4,3‐d]pyrimidine‐7(1H,‐6H)‐thione (14). Ammonolysis of 13 gave a low yield of the cytidine analogue 15. A chlorination of 7, followed by amination furnished an alternative route to 15. A similar glycosylation of TMS‐4 with 2,3,5‐tri‐O‐benzyl‐α‐D‐arabinofuranosyl chloride (16) gave mainly the N4 glycosylated product 17, which on debenzylation furnished 4‐β‐D‐arabinofuranosylpyrazolo[4,3‐d]pyrimidine‐5,7(1H,6H)‐dione (18). 7‐Amino‐4‐β‐D‐arabinofuranosylpyrazolo[4,3‐d]pyrimidin‐5(1H)‐one (23) was prepared from 17 via the pyridinium chloride intermediate 21. Condensation of the TMS derivative of pyrrolo[3,2‐d]pyrimidine‐2,4(1H,3H,5H)‐dione (24) with 6, followed by deprotection of the reaction product gave 1‐β‐D‐ribofuranosylpyrrolo[3,2‐d]pyrimidine‐2,4(3H,5H)‐dione (26). Similarly, TMS‐24 was reacted with 16 to give a mixture of the blocked nucleosides 31 and 32, which on debenzylation afforded a mixture of two isomeric compounds 34 and 35. 1‐β‐D‐Arabinofuranosylpyrrolo[3,2‐d]pyrimidine‐2,4(3H,5H)‐dione (34) was converted to the ara‐C analogue 38 via the 3‐nitrotriazolyl intermediate 36. The structure of 38 was confirmed by single crystal X‐ray diffraction studies.