Targeting of ribonucleotide reductase with 2'-Disulfide analogs of adenosine. Electronic versus steric effects in radical deoxygenation of fluorine-containing nucleosides

Authors

Dania Companioni, Florida International University

Document Type

Thesis

Degree

Master of Science (MS)

Major/Program

Chemistry

First Advisor's Name

Stanislaw F. Wnuk

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

David Becker

Third Advisor's Name

John T. Landrum

Date of Defense

5-24-2002

Abstract

Inhibition of the enzyme ribonucleotide reductase is an appealing concept for the rational drug design against rapid proliferation of systems such as viruses and cancer cells. Synthesis of 2'-thionucleoside analogs as possible inhibitors of the enzyme was targeted in this research. For protecting the reactive thiol group, mixed disulfides were prepared as precursors of the sulfur-containing nucleosides. The thionucleoside obtained are currently under biological studies.

Fluorinated compounds are widely used in biochemistry, medicinal chemistry, and pharmacology. Synthesis of 2'-deoxy-2'-fluoroadenosine and its arabino epimer as well as 3’-deoxy-3'-fluoroadenosine and its xylo epimer were also targeted in order to study the electronic versus steric β-fluorine effects in radical deoxygenation of fluorine containing pentofuranose nucleosides. Our results clearly show that steric effect of the heterocyclic base from the β-face of the sugar is decisive, favoring the incorporation of deuterium from the less hindered α-face.

Identifier

FI14060887

Comments

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Recommended Citation

Companioni, Dania, "Targeting of ribonucleotide reductase with 2'-Disulfide analogs of adenosine. Electronic versus steric effects in radical deoxygenation of fluorine-containing nucleosides" (2002). FIU Electronic Theses and Dissertations. 2417.
https://digitalcommons.fiu.edu/etd/2417