Vitamin B6 was discovered almost 90 years ago, and since then it has received a lot of interest from the scientific community due to its role in human health and its impact on several biochemical processes. One of the most interesting aspect of vitamin B6 studied in the past decade is its role in cancer. From the research on this subject so far, the following can be suggested: early-stage cancer cells have a higher vitamin B6 content than normal cells due to its role in metabolic processes. As the cancer makes progress, there is a change in vitamin B6 activation and trapping in the cell, decreasing the amount of active vitamin B6 in the cell in order to resist cell death. From these conclusions, we can see that vitamin B6 could potentially be an interesting radiotracer to use for diagnosis and staging of cancers. One of the most predominant form of imaging which is done nowadays to detect and diagnose cancers is Positron Emission Tomography (PET) imaging. Research on PET imaging is driven by the potential of new radiotracers which can be added to the current arsenal of tools for the fight against cancer. Therefore, this project focuses on the attempted synthesis of two potential radiotracers derived from vitamin B6 based on the insertion of fluorine-18. None of the two proposed radiotracers were successfully synthesized but we successfully synthesized one cold standard and difluorinated pyridoxine with cold conditions similar to radiochemistry. The main issues which were faced were the degradation of the potential precursors when attempting fluorination, the lack of reactivity of intermediates for the formation of precursors and an acetyl migration leading to the wrong precursors. By using a milder fluorination strategy to avoid degradation (room temperature, no free fluoride source: AgF2 as fluorinating agent), the 6-Fluoropyridoxine cold standard was synthesized. By changing the protection strategy (not using any acetyl groups), acetyl migration was avoided which led to the synthesis of a difluorinated pyridoxine using mild conditions (room temperature). The difluorination was also successful using harsher conditions (heat). There is still a lot of work to do to synthesize a radiotracer derived from vitamin B6 but there are some signs that this may be possible with additional work.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/43225 |
| Date | 27 January 2022 |
| Creators | Pinault-Masson, Émile |
| Contributors | Shuhendler, Adam |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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