Structural characterization of isoxazolidinyl nucleosides by fast atom bombardment tandem mass spectrometry.
4'-Aza-2',3'-dideoxyerythrofuranosyl derivatives of thymine (AdT, 1) and 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 isoxazolidine ring. The increasing importance of isoxazolidinyl nucleosides has encouraged the exploitation of simple mass spectrometric rules for unambiguously assigning their structure. The species 1, 2, 5 and 6 were therefore synthesized 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 fragment ions corresponding to [B + 2H](+),[M - BH](+) and [B + 27](+) species, where B is the nucleobase. The last species derives from a retrocycloaddition process which is less evident in 2'-deoxyribosides. This behaviour is consistent with protonation of the analytes at the pyrimidine rings. Model isoxazolidines, in which the nucleobase was replaced by a phenyl or a naphthyl moiety, displayed the expected behaviour of species with a localized charge on the N-O moiety of the isoxazolidine ring.
Colacino
E
E
Dipartimento di Chimica, Università della Calabria, via P. Bucci, cubo 15/c, I-87030 Arcavacata di Rende (CS), Italy.
Giorgi
G
G
Liguori
A
A
Napoli
A
A
Romeo
R
R
Salvini
L
L
Siciliano
C
C
Sindona
G
G
D000998:Antiviral Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007555:Isoxazoles / Q000138:chemical synthesis; D009705:Nucleosides / Q000138:chemical synthesis; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000998:Antiviral Agents; D007555:Isoxazoles; D009705:Nucleosides