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| Hauptseite > Publikationsdatenbank > Application of quaternary 1,4-diazabicyclo[2.2.2]octan (DABCO) salts for SN2 “minimalist” radiofluorination |
| Hauptseite > Publikationsdatenbank > Application of quaternary 1,4-diazabicyclo[2.2.2]octan (DABCO) salts for SN2 “minimalist” radiofluorination |
| Conference Presentation (After Call) | FZJ-2022-04641 |
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2022
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Please use a persistent id in citations: doi:10.1016/S0969-8051(22)00134-2
Abstract: Objectives: The piperazine scaffold is a privileged structuralmotif contained in numerous pharmaceuticals, including severalPET-tracers. The aim of this work was to evaluate quaternary DABCOsalts as precursors for the preparation of probes containing a N-(2-[18F]Fluoroethyl)piperazyl fragment by the “minimalist” approach.[1]The latter allows for the preparation of 18F-labeled compounds usingonly [18F]F– and onium salt precursors, obviating the need for externalbase, other additives and azeotropic drying.Methods: Quaternary DABCO salts were prepared by direct alkylation,(het)arylation, benzoylation or tosylation of DABCO. If necessary,anion metathesis was carried out. [18F]F– was eluted from ananion exchange resin with a solution of the corresponding DABCO saltin MeOH. MeOH was evaporated at 60°C for 8 min, the residue wastaken up into a suitable solvent and heated in a Monowave 50 (AntonPaar, Ostfildern-Scharnhausen, Germany) synthesis reactor. The radiolabelingprocedure was optimized with respect to reaction time,temperature, solvent and DABCO salt counter ion. Radiolabeled compoundsprepared from alkyl-substituted DABCO salts were isolatedby solid phase extraction (SPE). Additionally, N-(2-[18F]Fluoroethyl)-N’-pentynyl-piperazine ([18F]1) isolated by SPE was clicked withbenzyl azide (2) to afford a 18F-fluorinated model triazole ([18F]3).Results: Reaction of DABCO with alkyl halogenides or sulfonatesled to quaternary alkyl DABCO salts, radiofluorination of which under“minimalist” conditions furnished the corresponding ring openingproducts, N-alkyl-N’-(2-[18F]Fluoroethyl) piperazines, in 48–93%RCYs (determined by HPLC) and, after isolation by simple SPE, activityyields of up to 31%. Reaction of [18F]1 with 2 delivered [18F]3 in aquantitative RCY (determined by HPLC). (Het)arylation, benzoylationand tosylation of DABCO afforded the respective N’-substituted piperazyl-N-ethyl DABCO salts (addition products of two DABCO molecules)in up to 90% yields as single isolable products. 18F-Fluorinationof such substrates mainly occurred via substitution of the DABCOgroup, leading to formation of the corresponding radiofluorinatedN-substituted N’-(2-[18F]Fluoroethyl)piperazines in RCYs of 28–46%(determined by HPLC).Conclusions: Quaternary DABCO salts are efficient precursors forrapid preparation of probes containing an N-(2-[18F]Fluoroethyl)piperazinemotif using the simple and convenient “minimalist” protocol.Acknowledgement: This work was supported by the DFG grantZL 65/4-1.Reference:[1] B. D. Zlatopolskiy, et al.; Org. Biomol. Chem., 2014, 12, 8094.
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