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Structure determination of 4‐azido‐2‐pyrimidinone nucleoside analogs using mass spectrometry
Author(s) -
Wang Ping Ping,
Kotra Lakshmi P.,
Chu Chung K.,
Bartlett Michael G.
Publication year - 1999
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/(sici)1096-9888(199907)34:7<724::aid-jms820>3.0.co;2-t
Subject(s) - chemistry , mass spectrometry , nucleoside , chromatography , nucleoside analogue , stereochemistry
The nucleoside prodrugs 4‐azido‐ara‐C and 2′‐fluoro‐2′,3′‐dideoxy‐4‐azido‐ara‐C and their base‐catalyzed reaction products were thoroughly characterized by mass spectrometry. The structures of the base‐catalyzed reaction products were determined and confirmed using a combination of high‐resolution and tandem mass spectrometry with deuterium exchange. An intra‐molecular rearrangement reaction occured in 4‐azido‐ara‐C at physiological pH leading to the formation of a 2′,6‐anhydro product. A nucleoside of similar structure, 2′‐fluoro‐2′3′‐dideoxy‐4‐azido‐ara‐C was studied to determine if the formation of the 2′,6‐anhydro ring was due to the presence of the 4‐azido group or the arabinose 2′‐OH group. The 6‐position of 2′‐fluoro‐2′,3′‐dideoxy‐4‐azido‐ara‐C was found to be unreactive at physiological pH, but could add ammonia under strongly basic conditions (pH 11.0, ammonia solution). Finally, the formation of an intriguing tetrazole ring by the 4‐azido moiety was observed. Copyright © 1999 John Wiley & Sons, Ltd.