Synthesis and Biological Evaluation of 2'-Deoxyribonucleotide Analogs

Two new methods for the synthesis of 2'-deoxyribonucleosides have been developed. The first involves regioselective reductive deoxygenation of a suitably derivatized ribonucleoside. Tri-n-butyltin hydride reduction of a 2'-thiobenzoate derivative affords the desired 2'-deoxyribonucleoside in good yield. The second method for 2'-deoxyribonucleoside synthesis involves the stereoselective coupling of a derivatized 2-deoxyribofuranosyl bromide with heterocycles in the presence of silver tetrafluoroborate. These methods have been applied to the synthesis of 2'-deoxy-lin-benzoadenosine, a fluorescent deoxyribonucleotide analog. The analog was converted into the corresponding 5'-mono-, di-, and triphosphate derivatives. The diphosphate was found to be a substrate for phosphorylation by pyruvate kinase, and the triphosphate was found to be an acceptable replacement for 2'-deoxyadenosine-5'-triphosphate in DNA nick translation by E. coli DNA polymerase I.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Lessor, Ralph Arthur

• Chemistry, Organic

Identifier

(UMI)AAI8409802

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/70236