SYNTHESIS OF [N-15]GUANOSINES AND DEOXY[N-15]GUANOSINES FROM 5-AMINO-1-(BETA-D-RIBOFURANOSYL)IMIDAZOLE-4-CARBOXAMIDE (AICA-RIBOSIDE)

Methods are described for the syntheses of N-15-labelled guanosines and deoxyguanosines suitable for incorporation into oligonucleotides. The N-15 is located either at N-1 (e.g. [N-15(1)]guanosine la and deoxy[N-15(1)]guanosine 1b) or at the NH2 (e.g. [(NH2)-N-15]guanosine 1c and deoxy[(NH2)-N-15]guanosine Id). One of the synthetic methods starts from 5-amino-1-(beta-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 N-15 (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.