A NEW ROUTE TO N-15-LABELED, N-ALKYL, AND N-AMINO NUCLEOSIDES VIA N-NITRATION OF URIDINES AND INOSINES

A novel method for the specific [3-N-15]-labeling of pyrimidine nucleosides and [1-N-15]-labeling of purine nucleosides is reported, according to Scheme 1. The N-nitration reaction is carried out in good yields with nitronium trifluoroacetate in cold dichloromethane. Treatment of the resulting N-nitro nucleosides with (NH3)-N-15, alkylamines, or hydrazine cleaves the pyrimidine ring at room temperature, affording open intermediates which undergo cyclization to N-15-labeled, N-alkylated, or N-amino nucleosides, respectively. Preparation of [1-N-15]adenosine from inosine in a 52% overall yield is illustrative of the scope of the procedure. [3-N-15,(NH2)-N-15]-5'-O-Acetyl-3-amino-2',3'-O-isopropylideneuridine and [1-N-15, (NH2)-N-15]-2',3',5,-tri-O-acetyl-1-aminoinosine have also been obtained from double labeled hydrazine. By using a N-15-labeled substrate and/or N-15-labeled benzylamine it is shown that the amine attack takes mainly place at C4 of uridine and at C2 of inosine.