DEVELOPMENT OF NOVEL SPIN-LABELED NUCLEOSIDES

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We designed a new type of spin-labeled nucleosides with an N-tert-butyl aminoxyl raical which is introduced to nucleobase directly. Purine and pyrimidine nucleosides with aminoxyl radical were synthesized to investigate stability and behavior of N-tert-butyl aminoxyl radical on nucleobase.1) EPR spectra of 6-N-tert-butyl aminoxyl uridine (1a) and 6-N-tert-butyl aminoxyl cytidine (2a) were measured. The aN value of 2a decreased in the presence of 10 equiv. of guanosine derivatives (12.7 gauss) compared to that of 2a itself (13 gauss).2) In order to study EPR spectra of oligonucleotide containing 2'-deoxy 6-N-tert-butyl aminoxyl uridine (4), 3, the precursor of radical, was incorporated into 15-mer. Unfortunately, the Tm value of 15-mer containing 3 decreased considerably compared to natural type 15-mer and EPR studies of 4 containing oligonucleotide were not done.3) We planned to synthesis of 2'-deoxy 5-N-tert-hydroxylamino uridine (5) and 2-N-tert-hydroxylamino inosine (6), which might have anti conformation and their incorporation into oligonucleotide might not disturb stable duplex formation. We successfully synthesized 5 via metal halogen exchange reaction of 2'-deoxy 5-iodouridine sodium salts. We also synthesized 6.