An improved strategy for stereospecific late stage fluorination of a pyrimidine nucleoside at 2'-arabino position

• Main Authors: Ong, Sarah Diane C., Yu, Derrick Ethelert C., Nacario, Ruel C., Completo, Gladys C.
• Format: text
• Published: Animo Repository 2016
• Subjects: Pyrimidine nucleotides; Uridine; Tomography, Emission; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/8876
• 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 pharmadodynamics 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. 2'- (Fluoroarabinofuranosyl) uridine will be 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 will be 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 fluoride. An electron withdrawing protecting group (mesyl chloride or tosyl chloride) will be placed at 2' -OH position followed by the protection at N-3 position using di-tertbutyl dicarbonate. Late stage fluorination using KF will be employed via SN2 mechanism. The desired product could be synthesized in 4 to 5 steps. The proposed synthetic route will be performed under cold (nonradioactive conditions).