Efficient methods for the synthesis of [2-15N]guanosine and 2'-deoxy[2-15N]guanosine derivatives.
The nucleophilic addition-elimination reaction of 2',3',5'-tri-O-acetyl-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of triethylamine afforded the N2-benzyl[2-15N]guanosine derivative (13) in a high yield, which was further converted into the N2-benzoyl[2-15N] guanosine derivative by treatment with ruthenium trichloride and tetrabutylammonium periodate. A similar sequence of reactions of 2',3',5'-tri-O-acetyl-2-fluoro-06-[2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(beta-D-ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from guanosine, with potassium [15N]phthalimide afforded the N2-phthaloyl [2-15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-beta-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.
Kamaike
K
K
Laboratory of Pharmaceutical Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan. kamaikek@ps.toyaku.ac.jp
Kinoshita
K
K
Niwa
K
K
Hirose
K
K
Suzuki
K
K
Ishido
Y
Y
D002845:Chromatography; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D009587:Nitrogen Isotopes
D009587:Nitrogen Isotopes; D006151:Guanosine; D003849:Deoxyguanosine