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Synthesis of certain 3‐alkoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐ d ]pyrimidines structurally related to adenosine, inosine and guanosine
Author(s) -
Anderson Jack D.,
Dalley N. Kent,
Revankar Ganapathi R.,
Robins Roland K.
Publication year - 1986
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.5570230651
Subject(s) - chemistry , sodium methoxide , stereochemistry , guanosine , pyrimidine , glycosyl , alkoxy group , formamide , glycosylation , inosine , ring (chemistry) , adenosine , organic chemistry , methanol , biochemistry , alkyl
Several 3‐alkoxysubstituted pyrazolo[3,4‐ d ]pyrimidine ribonucleosides structurally related to adenosine, inosine and guanosine have been prepared by the direct glycosylation of preformed aglycon precursor containing a 3‐alkoxy substituent. Ring closure of 5(3)‐amino‐3(5)‐ethoxypyrazole‐4‐carboxamide ( 6b ) with either formamide or potassium ethyl xanthate gave 3‐ethoxyallopurinol ( 7b ) and 3‐ethoxy‐6‐thioxopyrazolo[3,4‐ d ]‐pyrimidin‐4(5 H ,7 H )‐one ( 10 ), respectively. Methylation of 10 gave the corresponding 6‐methylthio derivative 15 . Similar ring annulation of 5(3)‐methoxypyrazole‐4‐carboxamide ( 6a ) with formamide afforded 3‐methoxyallopurinol ( 7a ). Treatment of 5(3)‐amino‐3(5)‐methoxypyrazole‐4‐carbonitrile ( 5a ) with formamidine acetate furnished 4‐amino‐3‐methoxypyrazolo[3,4‐ d ]pyrimidine ( 4 ). High‐temperature glycosylation of 7b with 1‐ O ‐acetyl‐2,3,5‐tri‐ O ‐benzoyl‐D‐ribofuranose in the presence of boron trifluoride etherate gave a 2:1 mixture of N‐1 and N‐2 glycosyl blocked nucleosides 11b and 13b . Deprotection of 11b and 13b with sodium methoxide gave 3‐ethoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐ d ]pyrimidin‐4(5 H )‐one ( 12b ) and the corresponding N‐2 glycosyl isomer 14b , respectively. Similar glycosylation of either 4 or 7a , and subsequent debenzoylation gave exclusively 4‐amino‐3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐ d ]pyrimidine ( 9 ) and 3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐ d ]pyrimidin‐4‐(5 H )‐one ( 12a ), respectively. The structural assignment of 12a was made on the basis of single‐crystal X‐ray analysis. Application of this general glycosylation procedure to 15 gave the corresponding N‐1 glycosyl derivative 16 as the sole product, which on debenzoylation afforded 3‐ethoxy‐6‐(methylthio)‐1‐(3‐D‐ribofuranosylpyrazolo[3,4‐ d ]pyrimidin‐4(5 H )‐one ( 17 ). Oxidation of 16 and subsequent ammonolysis furnished the guanosine analog 6‐arnino‐3‐ethoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐ d ]‐pyrimidin‐4(5 H )‐one ( 19 ). Similarly, starting from 3‐methoxy‐4,6‐bis(methylthio)pyrazolo[3,4‐ d ]pyrimidine ( 20 ), 6‐amino‐3‐methoxy‐1‐β‐D‐ribofuranosylpyrazolo[3,4‐ d ]pyrimidin‐4(5 H )‐one ( 23 ) was prepared.