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 nucleo sides and [1-N-15]-labeling of purine nucleosides is reported, accordi ng 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 hy drazine cleaves the pyrimidine ring at room temperature, affording ope n intermediates which undergo cyclization to N-15-labeled, N-alkylated , or N-amino nucleosides, respectively. Preparation of [1-N-15]adenosi ne from inosine in a 52% overall yield is illustrative of the scope of the procedure. -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 b een obtained from double labeled hydrazine. By using a N-15-labeled su bstrate and/or N-15-labeled benzylamine it is shown that the amine att ack takes mainly place at C4 of uridine and at C2 of inosine.