This title appears in the Scientific Report :
2019
Please use the identifier:
http://hdl.handle.net/2128/23520 in citations.
Preparation of [18F]fluoroalkenyliodonium salts and their application for radiolabeling by cross‐coupling reactions
Preparation of [18F]fluoroalkenyliodonium salts and their application for radiolabeling by cross‐coupling reactions
Objective(Fluoroalkenyl)(aryl)iodonium salts are valuable building blocks for Pd‐catalyzed cross‐coupling reactions [1]. These prosthetic groups are easily available via nucleophilic addition of fluoride to the respective (alkynyl)(aryl)iodonium salts under exceptionally mild conditions [2]. Herein...
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Personal Name(s): | Humpert, Swen (Corresponding author) |
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Holschbach, Marcus / Bier, Dirk / Zlatopolskiy, Boris / Neumaier, Bernd | |
Contributing Institute: |
Nuklearchemie; INM-5 |
Imprint: |
2019
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Conference: | The 23rd International Symposium on Radiopharmaceutical Sciences, Beijing (China), 2019-05-26 - 2019-05-31 |
Document Type: |
Conference Presentation |
Research Program: |
Neuroimaging |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Objective(Fluoroalkenyl)(aryl)iodonium salts are valuable building blocks for Pd‐catalyzed cross‐coupling reactions [1]. These prosthetic groups are easily available via nucleophilic addition of fluoride to the respective (alkynyl)(aryl)iodonium salts under exceptionally mild conditions [2]. Herein we report the preparation of 18F‐labeled (2‐fluorohexen‐1‐yl)(aryl)iodonium salts ([18F]FHexI+X–) and their application in various Pd‐catalyzed cross‐coupling reactions. Finally, [18F]FHexI+OTs– was used for the site selective labeling of clinically relevant compounds and peptides.Methods(Alkynyl)(aryl)iodonium salts were radiolabeled using [18F]fluoride in aqueous media in the presence of different bases and K2.2.2. The reaction conditions were optimized with respect to different parameters including reaction temperature, time, solvent, precursor amount and counter ion. After isolation, [18F]FHexI+OTs– was applied in Pd‐catalyzed cross‐couplings with different model substrates. Additionally, radiofluorinated amino acid derivatives as well as a PSMA ligand potentially suitable for the detection of prostate carcinoma lesions were prepared starting from [18F]FHexI+OTs–.ResultsUnder optimized conditions (KHCO3, K2.2.2, 67% aq. DMSO, 75°C) [18F]FHexI+X– salts were prepared in RCYs of about 60% (HPLC) within 10 min. Remarkably, time consuming azeotropic drying was not necessary. Radiolabeling of the phenylethynyl substituted precursors also furnished the respective 18F‐labeled iodonium salts although in lower RCYs of 20% to 30% (HPLC). The respective counter ion (OTs–, OMs–, BF4–, TFA–) did not have a significant influence on RCYs. [18F]FHexI+OTs– was purified by HPLC followed by solvent exchange and thereafter used for subsequent cross‐coupling reactions. Sonogashira, Stille, and Suzuki reactions afforded the respective radiolabeled products as pure Z‐isomers in RCYs of 61% to 74% (HPLC) within 3 to 10 min at ambient temperature. In the case of the Heck cross‐coupling the corresponding 18F‐fluorinated diene was prepared in RCY of 27 ± 2% as a mixture of E/Z isomers.In particular, the one‐pot Sonogashira cross‐coupling reaction turned out to be very fast and robust under very mild conditions. Therefore, this reaction was selected to demonstrate the applicability of [18F]FHexI+ for the labeling of biomolecules. Nine ethynyl‐substituted amino acid derivatives were conjugated with [18F]FHexI+OTs– using the Sonogashira reaction affording the respective radiolabeled enynes in RCYs of 38% to 88% (HPLC). Furthermore, a novel 18F‐labeled PSMA ligand was prepared in an isolated RCY of 40% in two steps within 35 min. Conjugation of [18F]FHexI+OTs– to a suitably modified model dipeptide (H‐Arg‐Pra‐OBn) afforded the corresponding conjugate in 61% RCY based on isolated [18F]FHexI+OTs– using only 50 nmol peptide precursor.ConclusionThe novel radiolabeled prosthetic group [18F]FHexI+OTs– is easily available in aqueous media obviating any evaporation steps. Thus, [18F]FHexI+OTs– can be used in Pd‐catalyzed cross‐coupling reactions as a fast, high yielding, site specific and versatile procedure for the preparation of clinically relevant PET tracers. [1] Yoshida et al., Tetrahedron 62 (2006) 8636‐8645 [2] Nguyen et al., Tetrahedron 67 (2011) 3434‐34939image |