Synthesis of certain 3-alkoxy-1-β-D-ribofuranosylpyrazolo[3,4-d]pyrimidines structurally related to adenosine, inosine and guanosine

Autor: Roland K. Robins, N. Kent Dalley, Jack D. Anderson, Ganapathi R. Revankar
Rok vydání: 1986
Předmět:
Zdroj: Journal of Heterocyclic Chemistry. 23:1869-1878
ISSN: 1943-5193
0022-152X
Popis: 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(5H,7H)-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(5H)-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-(5H)-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(5H)-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(5H)-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(5H)-one (23) was prepared.
Databáze: OpenAIRE
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