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Synthesis of certain 1‐β‐D‐ribofuranosyl‐1,2‐dihydro‐2‐oxopyridines structurally related to nicotinamide ribonucleoside
Author(s) -
Haneem B.,
Joshi Ramachandra V.,
Larson Steven B.,
Robins Roland K.,
Revankar Ganapathi R.
Publication year - 1989
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.5570260656
Subject(s) - chemistry , ribonucleoside , nitrile , nicotinamide , trifluoromethanesulfonate , stereochemistry , substituent , trimethylsilyl , deoxyribonucleoside , ammonia , nucleoside , acetylation , yield (engineering) , medicinal chemistry , organic chemistry , catalysis , rna , biochemistry , materials science , metallurgy , gene , enzyme
Several substituted 1‐β‐D‐ribofuranosyl‐1,2‐dihydro‐2‐oxopyridines have been prepared as congeners of nicotinamide ribonucleoside. Direct glycosylation of the silylated 3‐ethylcarboxylate 5 or 3‐carbamoyl 6 derivative of 1,2‐dihydro‐2‐oxopyridine with 1,2,3,5‐tetra‐ O ‐acetyl‐β‐D‐ribofuranose ( 7 ) in the presence of trimethylsilyl triflate gave the corresponding blocked nucleosides 8 and 9 , respectively in good yield. Ammonolysis of 8 and 9 with methanolic ammonia furnished 1‐β‐D‐ribofuranosyl‐1,2‐dihydro‐2‐oxopyridine‐3‐carboxa‐mide ( 10 ), the structure of which was established by single‐crystal X‐ray diffraction analysis. Thiation of 9 with Lawesson's reagent and subsequent deacetylation of the thiated product 11 with methanolic ammonia furnished 1‐β‐D‐ribofuranosyl‐1,2‐dihydro‐2‐oxopyridine‐3‐thiocarboxamide ( 12 ). Modification of the carbo‐nitrile function of 1‐(2,3,5‐tri‐ O ‐acetyl‐β‐D‐ribofuranosyl)‐1,2‐dihydro‐2‐oxopyridine‐4‐carbonitrile ( 13 ) gave a series of 4‐substituted‐1‐β‐D‐ribofuranosyl‐1,2‐dihydro‐2‐oxopyridines, in which the 4‐substituent is a thiocarboxamide 15 , carboxamide 16 , carboxamidoxime 17 , carboxamidine 18 and aminomethyl 19 group. None of these compounds exhibited any significant antitumor or antiviral effects in vitro.