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Synthesis of certain exocyclic thiazole nucleosides related to tiazofurin. Formation of a unique acycloaminonucleoside
Author(s) -
Sanghvi Yogesh S.,
Larson Steven B.,
Robins Roland K.,
Revankar Ganapathi R.,
Gupta Pranab K.,
George Rose D.,
Dalley N. Kent
Publication year - 1988
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.5570250248
Subject(s) - chemistry , thiazole , carboxamide , thiourea , bromide , stereochemistry , sodium methoxide , nucleoside , carboxylate , medicinal chemistry , organic chemistry , methanol
Several thiazole nucleosides structurally related to tiazofurin (1) and ARPP (2) were prepared, in order to determine whether these nucleosides had enhanced antitumor/antiviral activities. Ring closure of 1‐(2,3,5‐tri‐ O ‐benzoyl‐β‐D‐ribofuranosyl)thiourea (4) with ethyl bromopyruvate (5a) gave ethyl 2‐(2,3,5‐tri‐ O ‐benzoyl‐β‐D‐ribofuranosylamino)thiazole‐4‐carboxylate (6a) . Treatment of 6a with sodium methoxide furnished methyl 2‐(β‐D‐ribopyranosylamino)thiazole‐4‐carboxylate (9) . Ammonolysis of the corresponding methyl ester of 6a gave a unique acycloaminonucleoside 2‐[(1 R , 2 R , 3 R , 4 R )(1‐benzamido‐2,3,4,5‐tetrahydroxypentane)amino]‐thiazole‐4‐carboxamide (7a) . Direct glycosylation of the sodium salt of ethyl 2‐mercaptothiazole‐4‐carboxylate (12) with 2,3,5‐tri‐ O ‐benzoyl‐D‐ribofuranosyl bromide (11) gave the protected nucleoside 10 , which on ammonolysis provided 2‐(β‐D‐ribofuranosylthio)thiazole‐4‐carboxamide (3b) . Similar glycosylation of 12 with 2‐deoxy‐3,5‐di‐ O ‐ p ‐toluoyl‐α‐D‐ erythro ‐pentofuranosyl chloride (13) , followed by ammonolysis gave 2‐(2‐deoxy‐β‐D‐ribofuranosylthio)thiazole‐4‐carboxamide (3c) . The structural assignments of 3b, 7a , and 9 were made by single‐crystal X‐ray analysis and their hydrogen bonding characteristics have been studied. These compounds are devoid of any significant antiviral/antitumor activity in vitro.