Synthesis of intermediates towards fluorination of pyrimidine-based nucleosides as positron emission tomography (PET) probes
Date of Publication
2016
Document Type
Master's Thesis
Degree Name
Master of Science in Chemistry
College
College of Science
Department/Unit
Chemistry
Thesis Adviser
Derrick Ethelbhert C. Yu
Defense Panel Chair
Jaime Raul O. Janairo
Defense Panel Member
Francisco C. Franco, Jr.
Ruel C. Nacario
Abstract/Summary
Radiolabeled fluorinated nucleosides are currently being used as a positron emission tomography (PET) probes. These molecular probes are injected into a research subject to examine specific biochemical and biological processes of a disease. It is also used to investigate in vivo pharmacokinetics and pharmacodynamics during drug discovery and development. However, current synthetic approaches of PET probes, involves a multi-step process that is extremely difficult, time-consuming and low yielding. Thus, an improved strategy is needed for the synthesis of positron-emitting nucleoside analog PET probes.
Intermediates to late stage fluorination were synthesized using a series of protection and deprotection at 2-, 3-, and 5- hydroxyl groups of ribose moiety and N-3 position of pyrimidine group of a preformed nucleoside uridine. A cyclic protecting group was first introduced at the 3'- and 5'-position of the ribose sugar to lock the ring in a rigid conformation where the uridine base is not sterically hindering and to permit the topside attack of a nucleophile during fluorination. Different electron withdrawing protecting group was placed at 2-OH position followed by the protection at N-3 position. Three intermediates of fully protected uridine were synthesized using DTBS, mesyl, acetyl, BOC, and triazole. These intermediates can then be used to improve a model system for the synthesis of fluorinated nucleosides.
Abstract Format
html
Language
English
Format
Electronic
Accession Number
CDTG006936
Shelf Location
Archives, The Learning Commons, 12F Henry Sy Sr. Hall
Physical Description
1 computer disc ; 4 3/4 in.
Keywords
Nucleosides; Tomography; Emission
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Recommended Citation
Ong, S. C. (2016). Synthesis of intermediates towards fluorination of pyrimidine-based nucleosides as positron emission tomography (PET) probes. Retrieved from https://animorepository.dlsu.edu.ph/etd_masteral/5336