Synthesis and Mass Spectrometric Fragmentation Characteristics of Imidazole Ribosides–Analogs of Intermediates of Purine De Novo Synthetic Pathway

Abstract

Two inherited deficiencies have been described in purine de novo synthesis pathway. Both the defects are diagnosed by detecting ribosides--dephosphorylated substrates of the enzymes--in patient's urine. We describe here a synthesis and mass spectrometric fragmentation of ribosides potentially of diagnostic importance for defects in the second part of the pathway. All the species, except 5-amino-4-imidazolesuccinocarboxamideriboside can be synthesized from the commercially available 5-amino-4-imidazolecarboxamideriboside by chemical methods. Fragmentation spectra of the compounds were obtained by the ion trap mass spectrometry. During fragmentation an opening of the imidazole ring was not observed for any of the compounds but loss of its substituents in the form of small molecules (NH3, CO2, CO) is the major route of fragmentation. The ribose moiety cleaves off molecule(s) of water, undergoes a cross-ring cleavage or breaks away as a whole.

Secondary processes in atmospheric pressure chemical ionization–ion trap mass spectrometry: a case study of orotic acid

“…Such events give rise to unexpected spectral peaks and can hamper comparability of the spectra with those acquired under different conditions. Previously, we reported on mass spectrometric analysis of purine and pyrimidine metabolites from the standpoint of their role in inborn errors of metabolism . For some of the analytes, we encountered certain remarkable phenomena occurring during the ionization or mass analysis that have significant effects on the appearance of resulting spectra.…”

“…Previously, we reported on mass spectrometric analysis of purine and pyrimidine metabolites from the standpoint of their role in inborn errors of metabolism. [22][23][24] For some of the analytes, we encountered certain remarkable phenomena occurring during the ionization or mass analysis that have significant effects on the appearance of resulting spectra. A similar uncommon behavior was later reported for guanine and guanosine by other authors.…”

Synthesis of Fluorinated Purine and 1-Deazapurine Glycosides as Potential Inhibitors of Adenosine Deaminase

“…Following the (natural) biosynthetic pathways for the synthesis of purine nucleotides, we have called these strategies de novo and salvage (Figure ). The first one is built on the regioselective electrophilic annulation of the pyridine and pyrimidine ring on the enamine moiety of the AIR-riboside using diverse fluorine-containing 1,3-CCC- and 1,3-CNC-dielectrophiles. The second strategy relies on the initial assembly of the CF 3 -containing purine/1-deazapurine framework starting with 5-aminoimidazole 8 which bears a p -methoxybenzyl (PMB) protecting group at position 9.…”

“…AIR-riboside 5a is a key substance in the de novo purine biosynthesis. Compound 5a , as well as its acylated derivative 5b , is unstable and very difficult to prepare . We have synthesized the corresponding nucleosides 5 and studied their reactions with the fluorinated 1,3-diketones 13 .…”

“…The main reason for the low yields lies in the fact that, in the case of compounds 5 , a Dimroth rearrangement takes place with formation of product 16 . We have also used a decarboxylation reaction of 12 , to generate 5 in situ in the presence of 1,3-diketones.…”