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Synthesis of 2′‐amino‐2′‐deoxy‐5‐fluorocytidine
Author(s) -
Sharma R. A.,
Bloch A.,
Bobek M.
Publication year - 1982
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.5570190533
Subject(s) - chemistry , acetic anhydride , sodium methoxide , acetylation , pyridine , in vitro , hela , substrate (aquarium) , organic chemistry , stereochemistry , biochemistry , catalysis , oceanography , gene , geology
Acetylation of 2′‐deoxy‐5‐fluoro‐2′‐trifluoroacetamidouridine with acetic anhydride in pyridine, followed by treatment with phosphorus pentasulfide in refluxing dioxane afforded 3′,5′‐di‐ O ‐acetyl‐2′‐deoxy‐5‐fluoro‐2′‐trifluorothioacetamido‐4‐thiouridine ( 3 ). Treatment of 3 with methanolic sodium methoxide furnished 2′‐deoxy‐2′‐trifluorothioacetamido‐4‐thiouridine ( 4 ), whereas its treatment with methanolic ammonia gave 2′‐amino‐2′‐deoxy‐5‐fluorocytidine ( 5 ). An alternative approach for the preparation of this compound proceeding from 2′‐trifluoroacetamidocytidine was unsuccessful, since the use of acetic anhydride in pyridine led to the replacement of the trifluoroacetyl function by an acetyl group, yielding an intermediate unsuitable for obtaining the target compound. The title compound was inactive at 1 × 10 −4 M concentration against HeLa and leukemia L1210 cells in vitro , but inhibited the in vitro growth of E. coli cells at a concentration of 1 × 10 −7 M . It was also found to be a substrate for CR/dCR deaminase partially purified from human liver, with a Km of 128 μ M .