Synthesis of intermediates towards fluorination of pyrimidine-based nucleosides as positron emission tomography (PET) probes

• Main Author: Ong, Sarah Diane C.
• Format: text
• Language: English
• Published: Animo Repository 2016
• Subjects: Nucleosides; Tomography; Emission
• Online Access: https://animorepository.dlsu.edu.ph/etd_masteral/5336
• Institution: De La Salle University

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.