A general copper-mediated nucleophilic 18F fluorination of arenes
Molecules labeled with fluorine-18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (SNAr) with [ 18F]F-. In the ideal case, the 18F fluorination of these substrates would be performed throu...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
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2014
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| _version_ | 1826306722886582272 |
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| author | Tredwell, M Preshlock, S Taylor, N Gruber, S Huiban, M Passchier, J Mercier, J Génicot, C Gouverneur, V |
| author_facet | Tredwell, M Preshlock, S Taylor, N Gruber, S Huiban, M Passchier, J Mercier, J Génicot, C Gouverneur, V |
| author_sort | Tredwell, M |
| collection | OXFORD |
| description | Molecules labeled with fluorine-18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (SNAr) with [ 18F]F-. In the ideal case, the 18F fluorination of these substrates would be performed through reaction of [18F]KF with shelf-stable readily available precursors using a broadly applicable method suitable for automation. Herein, we describe the realization of these requirements with the production of 18F arenes from pinacol-derived aryl boronic esters (arylBPin) upon treatment with [18F]KF/K 222 and [Cu(OTf)2(py)4] (OTf= trifluoromethanesulfonate, py=pyridine). This method tolerates electron-poor and electron-rich arenes and various functional groups, and allows access to 6-[18F]fluoro-L-DOPA, 6-[18F]fluoro-m-tyrosine, and the translocator protein (TSPO) PET ligand [18F]DAA1106. 18F-labeling for PET: The nucleophilic 18F fluorination of pinacol-derived aryl boronic esters is achieved with [18F]KF/K 222 in the presence of [Cu(OTf)2(py)4] (OTf=trifluoromethanesulfonate, py=pyridine); this unprecedented method can produce a clinical dose of 6-[18F]fluoro-L-DOPA in two steps (fluorination followed by deprotection) from a readily available shelf-stable arylBPin precursor (see scheme). RCY=decay-corrected radiochemical yield © 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. |
| first_indexed | 2024-03-07T06:52:16Z |
| format | Journal article |
| id | oxford-uuid:fced02e8-1335-4d3e-81e6-e9bbfb906b0f |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:52:16Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:fced02e8-1335-4d3e-81e6-e9bbfb906b0f2022-03-27T13:24:58ZA general copper-mediated nucleophilic 18F fluorination of arenesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fced02e8-1335-4d3e-81e6-e9bbfb906b0fSymplectic Elements at Oxford2014Tredwell, MPreshlock, STaylor, NGruber, SHuiban, MPasschier, JMercier, JGénicot, CGouverneur, VMolecules labeled with fluorine-18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (SNAr) with [ 18F]F-. In the ideal case, the 18F fluorination of these substrates would be performed through reaction of [18F]KF with shelf-stable readily available precursors using a broadly applicable method suitable for automation. Herein, we describe the realization of these requirements with the production of 18F arenes from pinacol-derived aryl boronic esters (arylBPin) upon treatment with [18F]KF/K 222 and [Cu(OTf)2(py)4] (OTf= trifluoromethanesulfonate, py=pyridine). This method tolerates electron-poor and electron-rich arenes and various functional groups, and allows access to 6-[18F]fluoro-L-DOPA, 6-[18F]fluoro-m-tyrosine, and the translocator protein (TSPO) PET ligand [18F]DAA1106. 18F-labeling for PET: The nucleophilic 18F fluorination of pinacol-derived aryl boronic esters is achieved with [18F]KF/K 222 in the presence of [Cu(OTf)2(py)4] (OTf=trifluoromethanesulfonate, py=pyridine); this unprecedented method can produce a clinical dose of 6-[18F]fluoro-L-DOPA in two steps (fluorination followed by deprotection) from a readily available shelf-stable arylBPin precursor (see scheme). RCY=decay-corrected radiochemical yield © 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. |
| spellingShingle | Tredwell, M Preshlock, S Taylor, N Gruber, S Huiban, M Passchier, J Mercier, J Génicot, C Gouverneur, V A general copper-mediated nucleophilic 18F fluorination of arenes |
| title | A general copper-mediated nucleophilic 18F fluorination of arenes |
| title_full | A general copper-mediated nucleophilic 18F fluorination of arenes |
| title_fullStr | A general copper-mediated nucleophilic 18F fluorination of arenes |
| title_full_unstemmed | A general copper-mediated nucleophilic 18F fluorination of arenes |
| title_short | A general copper-mediated nucleophilic 18F fluorination of arenes |
| title_sort | general copper mediated nucleophilic 18f fluorination of arenes |
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