This work improved the radiosynthesis of a known M2 muscarinic receptor imaging agent, [18F]FP-TZTP, and subsequent syntheses and in vitro evaluation of several novel TZTP derivatives highlighted a lead compound which exhibited M4 potency and selectivity, the thioether fluoro-polyethyleneglycol, which was then adapted for radiolabelling (23% radiochemical yield (uncorrected), >99% radiochemical purity, reaction time of 37 minutes). The present study also seeked to utilize aziridines as intermediates in [18F]-radiolabelling chemistry for the facile radiosynthesis of [18F]-labelled beta-blockers. Novel [18F]-labelled amines were synthesized via ring-opening and deprotection to yield the [18F]-1-fluoro-2-propanamine moiety (85%) favourably over the regioisomer [18F]-2-fluoro-1-propanamine (15%). Subsequent attempts to use these amine synthons in the synthesis of the beta-blocker [18F]Exaprolol resulted in poor radiochemical yields (1-3%). The chemistry of aziridine ring-opening with 19F-fluoride sources was thoroughly explored in order to understand the fundamentals of this chemistry, and the 1-fluoro-2-propanamine moiety was characterized by X-ray crystallography and NMR spectroscopy.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17719 |
| Date | 22 September 2009 |
| Creators | van Oosten, Erik |
| Contributors | Vasdev, Neil, Yudin, Andrei |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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