Efficient methods for the synthesis of [2-N-15]guanosine and 2 '-deoxy[2-N-15]guanosine derivatives

The nucleophlic addition-elimination reaction of 2',3',5'-tri-O-acety-2-flu oro-O-6- [2-(4-nitrophenyl)ethyl] inosine (8) with [N-15]benzylamine in the presence of triethylamine afforded the N-2-benzyl[2-N-15]guanosine derivat ive (13) in a high yield, which was further converted into the N-2-benzoyl[ 2-N-15] guanosine derivative by treatment with ruthenium trichloride and te trabutylammonium periodate. A similar sequence of reactions of 2',3',5-tri- O-acety-2-fluoro-O-6- [2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-f luoro-9-(beta -ribofuranosyl)-9H-purine derivative (11), which were respect ively prepared from guanosine, with potassium [N-15]phthalimide afforded th e N-2-phthaloyl [2-N-15]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-a cetyl-beta -D-ribofuranosyl)-6-chloro-2- [N-15]phthalimido-9H-purine (17; 6 4%), respectively Compounds 15 and 17 were then efficiently converted into 2',3',5'-tri-O-acetyl [2-N-15]guanosine. The corresponding 2'-deoxy derivat ives (16 and 18) were also synthesized through similar procedures.