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Synthesis of β‐D‐ribo‐ and 2′‐deoxy‐β‐D‐ribofuranosyl derivatives of 6‐aminopyrazolo[4,3‐ c ]pyridin‐4(5 H )‐one by a ring closure of pyrazole nucleoside precursors
Author(s) -
Gupta Pranab K.,
Kent Dalley N.,
Robins Roland K.,
Revankar Ganapathi R.
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.5570230112
Subject(s) - chemistry , ring (chemistry) , pyrazole , stereochemistry , glycosylation , bromide , glycosyl , nucleoside , ribonucleoside , anomer , medicinal chemistry , organic chemistry , rna , biochemistry , gene
6‐Amino‐1‐(2‐deoxy‐β‐D‐ erthro ‐pentofuranosyl)pyrazolo[4,3‐ c ]pyridin‐4(5 H )‐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(5 H )‐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(5 H )‐one 5′‐phosphate ( 19 ). The site of glycosylation and the anomeric configuration of these nucleosides have been assigned on the basis of 1 H nmr and uv spectral characteristics and by single‐crystal X‐ray analysis of 16 .