EFFICIENT METHODS FOR THE SYNTHESIS OF [2-15N]GUANOSINE AND 2′-DEOXY[2-15N]GUANOSINE DERIVATIVES

Abstract

The nucleophilic addition–elimination reaction of 2′,3′,5′-tri-O-acetyl-2-fluoro-O 6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of triethylamine afforded the N 2-benzyl[2-15N]guanosine derivative (13) in a high yield, which was further converted into the N 2-benzoyl[2-15N] guanosine derivative by treatment with ruthenium trichloride and tetrabutyl-ammonium periodate. A similar sequence of reactions of 2′,3′,5′-tri-O-acetyl-2-fluoro-O 6-[2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(β-D-ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from guanosine, with potassium [15N]phthalimide afforded the N 2-phthaloyl [2-15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-[15N]phthalimido-9H-purine (17; 64%), respectively. Compounds 15 and 17 were then efficiently converted into 2′,3′,5′-tri-O-acetyl[2-15N]guanosine. The corresponding 2′-deoxy derivatives (16 and 18) were also synthesized through similar procedures.