Structure determination of 4-azido-2-pyrimidinone nucleoside analogs using mass spectrometry

✍ Scribed by Wang, Ping Ping; Kotra, Lakshmi P.; Chu, Chung K.; Bartlett, Michael G.

• Book ID: 101223449
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 123 KB
• Volume: 34
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(199907)34:7<724::aid-jms820>3.0.co;2-t

✦ Synopsis

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, 2fluoro-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.