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Synthesis of 4,6‐disubstituted‐7‐β‐D‐ribofuranosyl‐ and arabinofuranosylpyrazolo[3,4‐ d ]pyrimidines and certain related ribonucleosides
Author(s) -
Rao T. Sudhakar,
Revankar Ganapathi R.,
Vinayak Ravi S.,
Robins Roland K.
Publication year - 1991
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570280722
Subject(s) - chemistry , pyrimidine , cytidine , nucleoside , pyridinium , ribonucleoside , yield (engineering) , stereochemistry , uridine , chloride , glycosylation , trimethylsilyl , medicinal chemistry , organic chemistry , biochemistry , rna , materials science , metallurgy , gene , enzyme
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(1 H ,5 H ,7 H )‐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(1 H ,5 H )‐dione ( 6 ). Debenzoylation of 6 gave the uridine analog 7‐β‐D‐ribofuranosylpyrazolo[3,4‐ d ]pyrimidine‐4,6(1 H ,5 H )‐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(1 H ,5 H )‐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(1 H )‐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(1 H ,5 H )‐dione ( 14 ). 4‐Amino‐7‐β‐D‐arabinofuranosyl‐pyrazolo[3,4‐ d ]pyrimidin‐6(1 H )‐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(4 H )‐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‐(4 H ,6 H )‐dione ( 29 ), 2‐amino‐4‐β‐D‐ribofuranosylthiazolo[4,5‐ d ]pyrimidine‐5,7(6 H )‐dione ( 28 ) has been prepared. The structure of 25 was confirmed by single crystal X‐ray diffraction studies.