Dissertations and Theses
Date of Award
2024
Document Type
Thesis
Department
Biology
First Advisor
Mahesh K. Lakshman
Second Advisor
Mark Pezzano
Third Advisor
Karen Hubbard
Keywords
Pyrimidine nucleoside analogous
Abstract
Briefly, the following report details a synthetic route to prepare 5-phenyl-2’-deoxycytidine analogues. This multistep synthesis began with silyl protection of the 3’- and 5’-hydroxyl groups of 5-iodo-2’-deoxyuridine. Next, the installation of a phenyl ring at the C5 position of the nucleobase via a Suzuki-Miyaura cross-coupling reaction, yielding 5-phenyl-2’-deoxyuridine (5-PdU). After that, modification of the obtained 5-PdU at the C4 position was performed with benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP, a peptide-coupling agent) and a base (cesium carbonate) to activate the amide group of the uridine nucleobase for subsequent displacement with a variety of amines. Modification of the C4 position resulted in protected 5-phenyl-2’-deoxycytidine (5-PdC) derivatives. To complete the synthesis, the 3’- and 5’-silyl groups were removed by a fluoride source (n-tetrabutylammonium fluoride, TBAF) to generate unprotected 5-PdC analogues. Additionally, potential enzymes that may recognize the 5-PdC analogues and a proposed evaluation of the 5-PdC analogues’ biological properties have been presented.
Recommended Citation
Persaud, Kevin E., "Synthesis of Novel 5-Aryl 2’-Deoxyuridine and 2’-Deoxycytidine Analogues" (2024). CUNY Academic Works.
https://academicworks.cuny.edu/cc_etds_theses/1176