Structural characterization of isoxazolidinyl nucleosides by fast atom bombardment tandem mass spectrometry

4 ' -Aza-2 ' ,3 ' -dideoxyerythrofuranosyl derivatives of thymine (AdT,1) a nd uracil (AdU, 2) are analogues of 2 ' ,3 ' -dideoxyribofuranosyl thymine (ddT, 3) and uracyl (ddU, 4). Compounds 1 and 2 are representative of a new class of antiviral agents where the sugar moiety is replaced by an isoxazo lidine ring. The increasing importance of isoxazolidinyl nucleosides has en couraged the exploitation of simple mass spectrometric rules for unambiguou sly assigning their structure. The species 1, 2, 5 and 6 were therefore syn thesized in order to evaluate the role of the basic centre of the modified sugar moiety in their gas-phase chemistry. The tandem mass spectra of these compounds are similar to those of the wild-type nucleosides and display fr agment ions corresponding to [B + 2H](+), [M - BH](+) and [B + 27](+) speci es, where B is the nucleobase. The last species derives from a retrocycload dition process which is less evident in 2 ' -deoxyribosides. This behaviour is consistent with protonation of the analytes at the pyrimidine rings. Mo del isoxazolidines, in which the nucleobase was replaced by a phenyl or a n aphthyl moiety, displayed the expected behaviour of species with a localize d charge on the N-O moiety of the isoxazolidine ring. Copyright (C) 2001 Jo hn Wiley & Sons, Ltd.