Synthesis of 4,6‐disubstituted‐7‐β‐D‐ribofuranosyl‐ and arabinofuranosylpyrazolo[3,4‐d]pyrimidines and certain related ribonucleosides

Several disubstituted pyrazolo[3,4-d]pyrimidine, pyrazolo[1,5-a]pyrimidine and thiazolo[4,5-d]pyrimidine ribonucleosides have been prepared as congeners of uridine and cytidine. Glycosylation of the trimethylsilyl (TMS) derivative of pyrazolo[3,4-d]pyrimidine-4,6(1H,5H,7H)-dione (4) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose (5) in the presence of TMS triflate afforded 7-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrazolo-[3,4-d]pyrimidine-4,6(1H,5H)-dione (6). Debenzoylation of 6 gave the uridine analog 7-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidine-4,6(1H,5H)-dione (3), identical with 7-ribofuranosyloxoallopurinol reported earlier. Thiation of 6 gave 7, which on debenzoylation afforded 7-β-D-ribofuranosyl-6-oxopyrazolo[3,4-d]pyrimidine-4(1H,5H)-thione (8). Ammonolysis of 7 at elevated temperature gave a low yield of the cytidine analog 4-amino-7-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidin-6(1H)-one (11). Chlorination of 6, followed by ammonolysis, furnished an alternate route to 11. A similar glycosylation of TMS-4 with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride (12) gave mainly the N7-glycosylated product 13, which on debenzylation provided 7-β-D-arabinofuranosylpyrazolo[3,4-d]pyrimidine-4,6(1H,5H)-dione (14). 4-Amino-7-β-D-arabinofuranosyl-pyrazolo[3,4-d]pyrimidin-6(1H)-one (19) was prepared from 13 via the C4-pyridinium chloride intermediate 17. Condensation of the TMS derivatives of 7-hydroxy- (20) or 7-aminopyrazolo[1,5-a]pyrimidin-5(4H)-one (23) with 5 in the presence of TMS triflate gave the corresponding blocked nucleosides 21 and 24, respectively, which on deprotection afforded 7-hydroxy- 22 and 7-amino-4-β-D-ribofuranosylpyrazolo[1,5-a]pyrimidin-5-one (25), respectively. Similarly, starting either from 2-chloro (26) or 2-aminothiazolo[4,5-d]pyrimidine-5,7-(4H,6H)-dione (29), 2-amino-4-β-D-ribofuranosylthiazolo[4,5-d]pyrimidine-5,7(6H)-dione (28) has been prepared. The structure of 25 was confirmed by single crystal X-ray diffraction studies.