Document Type



Master of Science (MS)



First Advisor's Name

Stanislaw F. Wnuk

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Leonard Keller

Third Advisor's Name

Kevin O'Shea

Date of Defense



Inactivation of ribonucleotide reductases by 2'-azido-2'-deoxynucleotides is accompanied by appearance of new EPR signals for a nitrogen-centered radical. The structure of this elusive nitrogen-centered radical has been studied extensively and shown to be derived from azide moiety. Synthesis of 3'[17 O]-labeled 2'-azido-2'-deoxyuridine-5'- diphosphate was targeted in this research. Such a labeled analogue should perturb the EPR spectrum in predictable fashion, and the hyperfine interaction between the free electron and the 17O nucleus should allow the choice between the recently proposed structures of this elusive radical (Van Der Donk, W. A. et al. J Am. Chem. Soc. 1995, 117, 8908-8916).

The labeled 2'-azido-2'-deoxynucleotides was prepared by thermolysis of O2,3'- anhydrouridine to give the more stable O2,2'-anhydrouridine derivatives with concomitant rearrangement of the 2'-O-benzoyl[17O] group into the 3'-[17O]-benzoyl intermediate. Deprotection and ring opening with LiF/Me3SiN3 gave the 3'[17O]-2--azido 2'-deoxyuridine. Tosylation (O5') and displacement of the 5'-tosylate by treatment with tris(tetra-n-butylarmonium) hydrogen pyrophosphate gave 3'[17O]-2'-azido-2'- deoxyuridine 5'-diphosphate. All the intermediates and the products were characterized by 1H-NMR, 13C-NMR, 3IP-NMR and isotopic enhancement was confirmed by using mass spectrometry.




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