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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