<p>Methods for the <sup>11</sup>C-labeling of carbonyl compounds applicable in the preparation of radiotracers for Positron Emission Tomography (PET) are described. To this end [<sup>11</sup>C]carbon monoxide at low concentration was used in transition metal- mediated reactions.</p><p>Stille couplings were employed in the synthesis of [<i>carbonyl-</i><sup>11</sup>C]ketones from methyl and aryl halides with [<sup>11</sup>C]carbon monoxide. The synthesized [<i>carbonyl-</i><sup>11</sup>C]ketones were obtained from the corresponding organostannanes with analytical radiochemical yields up to 98%.</p><p>A number of synthetic routes were designed using [<sup>11</sup>C]carbon monoxide and rhodium complexes. Nitrene intermediates were generated from azides and reacted via a rhodium-mediated carbonylation reaction as a general synthetic route to [<i>carbonyl-</i><sup>11</sup>C]isocyanates, versatile precursors. [<i>carbonyl-</i><sup>11</sup>C]Isocyanate reacted via nucleophilic attack of an amine to form <i>N,N’</i>-diphenyl[<sup>11</sup>C]urea in 82% analytical radiochemical yield, ethyl phenyl[<sup>11</sup>C]carbamate was synthesized by the same route, using ethanol as the nucleophile, in 70% radiochemical yield. [<sup>11</sup>C]Isocyanate was also able to react in a [2+3] cycloaddition with ethylene oxide to form 3-phenyl[<i>carbonyl-</i><sup>11</sup>C]oxazolidin-2-one in over 80% analytical radiochemical yield. This method was applied to the synthesis of a potential efflux system tracer [<sup>11</sup>C]hydroxyurea in 38% isolated radiochemical yield and the derivative 1-hydroxy-3-phenyl[<sup>11</sup>C]urea in 35% isolated radiochemical yield. Carbene intermediates, generated from diazo compounds, were reacted with [<sup>11</sup>C]carbon monoxide in the rhodium-mediated synthesis of [<i>carbonyl-</i><sup>11</sup>C]ketenes. [<i>carbonyl-</i><sup>11</sup>C]Ketene intermediates were utilised in the synthesis of diethyl[<i>carbonyl</i>-<sup>11</sup>C]malonate, from ethyl diazoacetate and ethanol. The product was obtained with a 20% isolated radiochemical yield. Alkylation of diethyl[<i>carbonyl</i>-<sup>11</sup>C]malonate, with ethyliodide and tetrabutylammonium fluoride, was successfully accomplished and diethyl diethyl[<i>carbonyl</i>-<sup>11</sup>C]malonate was synthesized in 50% analytical radiochemical yield. Several (<i>carbonyl-</i><sup>13</sup>C)compounds were also synthesized using the described methods as a way of characterizing the position of the label using <sup>13</sup>C-NMR.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-6654 |
| Date | January 2006 |
| Creators | Barletta, Julien |
| Publisher | Uppsala University, Department of Biochemistry and Organic Chemistry, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 ; 156 |
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