Synthesis of certain pyrazolo[3,4‐d]pyrimidin‐3‐one nucleosides

Synthesis of the pyrazolo[3,4‐d]pyrimidin‐3‐one congeners of guanosine, adenosine and inosine is described. Glycosylation of 3‐methoxy‐6‐methylthio‐1H‐pyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (13) with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐D‐ribofuranose (16) in the presence of boron trifluoride etherate gave 3‐methoxy‐6‐methylthio‐1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)pyrazolo[3,4‐d]pyrimidin‐4(5H)‐one (17) which, after successive treatments with 3‐chloroperoxybenzoic acid and methanolic ammonia, afforded 6‐amino‐3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐4(5H)one (18). The guanosine analog, 6‐amino‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidine‐3,4(2H,5H)‐dione (21), was made by sodium iodide‐chlorotrimethylsilane treatment of 6‐amino‐3‐methoxy‐1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrazolo[3,4‐d]pyrimidin‐4(5H)one (19), followed by sugar deprotection. Treatment of the adenine analog, 4‐amino‐1H‐pyrazolo[3,4‐d]pyrimidin‐3(2H)‐one (11), according to the high temperature glycosylation procedure yielded a mixture of N‐1 and N‐2 ribosyl‐attached isomers. Deprotection of the individual isomers afforded 4‐amino‐3‐hydroxy‐1‐βribofuranosylpyrazolo‐[3,4‐d]pyrimidine (26) and 4‐amino‐2‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidin‐3(7H)‐one (27). The structures of 26 and 27 were established by single crystal X‐ray diffraction analysis. The inosine analog, 1‐β‐D‐ribofuranosylpyrazolo[3,4‐d]pyrimidine‐3,4(2H,5H)‐dione (28), was synthesized enzymatically by direct ribosylation of 1H‐pyrazolo[3,4‐d]pyrimidine‐3,4(2H,5H)‐dione (8) with ribose‐1‐phosphate in the presence of purine nucleoside phosphorylase, and also by deamination of 26 with adenosine deaminase.