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)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/29668 |
| Date | 09 1900 |
| Creators | Ashique, Rezwan |
| Contributors | Chirakal, R. V., Schrobilgen, G. J., Chemistry |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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