Synthesis of β-D-ribo- and 2′-deoxy-β-D-ribofuranosyl derivatives of 6-aminopyrazolo[4,3-c]pyridin-4(5H)-one by a ring closure of pyrazole nucleoside precursors

Autor: N. Kent Dalley, G. R. Revankar, Pranab K. Gupta, Roland K. Robins
Rok vydání: 1986
Předmět:
Zdroj: Journal of Heterocyclic Chemistry. 23:59-64
ISSN: 1943-5193
0022-152X
DOI: 10.1002/jhet.5570230112
Popis: 6-Amino-1-(2-deoxy-β-D-erthro-pentofuranosyl)pyrazolo[4,3-c]pyridin-4(5H)-one (5), as well as 2-(β-D-ribofuranosyl)- and 2-(2-deoxy-β-D-ribofuranosyl)- derivatives of 6-aminopyrazolo[4,3-c]pyridin-4(5H)-one (18 and 22, respectively) have been synthesized by a base-catalyzed ring closure of pyrazole nucleoside precursors. Glycosylation of the sodium salt of methyl 3(5)-cyanomethylpyrazole-4-carboxylate (6) with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose (8) provided the corresponding N-1 and N-2 glycosyl derivatives (9 and 10, respectively). Debenzoylation of 9 and 10 with sodium methoxide gave deprotected nucleosides 14 and 16, respectively. Further ammonolysis of 14 and 16 afforded 5(or 3)-cyanomethyl-1-(2-deoxy-β-D-erythro-pentofuranosyl)pyrazole-4-carboxamide (15 and 17, respectively). Ring closure of 15 and 17 in the presence of sodium carbonate gave 5 and 22, respectively. By contrast, glycosylation of the sodium salt of 6 with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide (11) or the persilylated 6 with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose gave mainly the N-2 glycosylated derivative 13, which on ammonolysis and ring closure furnished 18. Phosphorylation of 18 gave 6-amino-2-β-D-ribofuranosylpyrazolo[4,3-c]pyridin-4(5H)-one 5′-phosphate (19). The site of glycosylation and the anomeric configuration of these nucleosides have been assigned on the basis of 1H nmr and uv spectral characteristics and by single-crystal X-ray analysis of 16.
Databáze: OpenAIRE