Synthesis of [15N]guanosines and deoxy[15N]guanosines from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (‘AICA-riboside’)

Abstract

Methods are described for the syntheses of ¹⁵N-labelled guanosines and deoxyguanosines, suitable for incorporation into oligonucleotides. The ¹⁵N is located either at N-1 (e.g.[¹⁵N¹]guanosine 1a and deoxy[¹⁵N¹]guanosine 1b) or at the NH₂(e.g.[¹⁵NH₂]guanosine 1c and deoxy[¹⁵NH₂]guanosine 1d). One of the synthetic methods starts from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (AICA-riboside, 2a) and leads via a cyclonucleoside to mixtures of compounds 1a and 1c, in which either compound predominates depending on the source of ¹⁵N (ammonia or benzoyl isothiocyanate). The other method utilises the same starting material, but a different mode of formation of the pyrimidine ring and yields either guanosine 1a or 1c(as its 2-N-benzoyl derivative 8b), exclusively.