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Electrophilic Fluorination of 3,4,6-tri-O-acetyl-D-glucal in Anhydrous Hydrogen Fluoride: Synthesis of 2-fluoro-2-deoxy-ß-D-allose, A Potential PET Radiotracer for Breast Tumour

In light of the increasing interest in the syntheses of fluorocarbohydrates as well as in their radiolabelled analogues for use in positron emission tomography (PET), a two- step synthesis of 2-fluoro-2-deoxy-ß-D-allose (2-FDpA) has been developed. The present synthesis employed electrophilic fluorination of 3,4,6-tri-O-acetyl-D-glucal in anhydrous HF (aHF) solvent using F2 and AcOF and was more rapid and efficient than the existing synthesis of 2-deoxy-2-fluoro-D-allose, with a total synthesis time of approximately 45 min, and less laborious. The synthesis proved to be higly regio- and Stereosective, which is often hard to achieve from electrophilic fluorinations.
The synthetic route to 2-FDßA was used to obtain the 18F-Iabelled analogue, 2-[18F]FDßA, for the first time with the anticipation that the labelled compound will be of use as a diagnostic agent for the detection and assessment of different tumours as well as for monitoring D-allose metabolism. The overall decay-corrected radiochemical yields (RCY) of the products resulting from radiofluorination of TAG in aHF with [18F]F2 and [18F]AcOF were 33 ±3% and 9 ±2%, respectively, with respect to [18FJF2. The RCY of 33 ±3% is the highest reported for direct fluorinations of TAG using [18FJF2 in any solvent. The radiochemical purities of 2-[18F]FDßA were 96 ±3% and 91 ±8% as determined by radio-HPLC and radio-TLC, respectively. Preliminary in vivo studies using normal rats showed significant differences between the uptake of 2-[18F]FDßA and 2-[18F]FDG, the most commonly used PET radiotracer for detection of various types of cancers. In addition, an animal study with a Polynoma Middle T mouse showed retention of 2-[18F]FDßA in the tumour. The 18F-Iabelling technique was also used as a mechanistic probe for the synthesis of 2-FDßA in the present study. / Thesis / Master of Science (MSc)

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29668
Date09 1900
CreatorsAshique, Rezwan
ContributorsChirakal, R. V., Schrobilgen, G. J., Chemistry
Source SetsMcMaster University
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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