Structure determination of 4-azido-2-pyrimidinone nucleoside analogs usingmass spectrometry

The nucleoside prodrugs 4-azido-ara-C and 2'-fluoro-2',3/-dideoxy-4-azido-a ra-C and their base catalyzed reaction products were thoroughly characteriz ed by mass spectrometry. The structures of the base-catalyzed reaction prod ucts were determined and confirmed using a combination of high-resolution a nd tandem mass spectrometry,vith deuterium exchange. An intra-molecular rea rrangement 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-3-azido-ara-C was studied to determine if the form ation 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 a mmonia under strongly basic conditions (pH 11.0, ammonia solution). Finally , the formation of an intriguing tetrazole ring by the 4-azido moiety was o bserved. Copyright (C) 1999 John Wiley & Sons, Ltd.