Alcohol-Supported Cu-Mediated 18F-Fluorination of Iodonium Salts under “Minimalist” Conditions
Abstract
1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. General
3.2. Nuclear Magnetic Resonance
3.3. Mass Spectroscopy
3.4. Chemistry
3.4.1. (S,S)-Ni-BPB-3-IPhe (14)
3.4.2. Boc-3IPhe-OtBu (15)
3.4.3. 3-{2-[(2S)-2-{[(tert-Butoxy)carbonyl]amino}-3-(tert-butoxy)-3-oxopropyl]phenyl}(2,4,6-trime-thylphenyl)iodanium tetrafluoroborate (12)
3.5. Radiochemistry
3.5.1. General
3.5.2. TLC Analysis
3.5.3. HPLC Analysis
3.5.4. Determination of Enantiomeric Purity
3.5.5. Manual Radiosynthesis. Screening of the Reaction Conditions and Reaction Scope—General Procedure 1 (GP 1)
3.5.6. Manual Radiosynthesis. Preparation of 2-[18F]FPhe ([18F]8) and 4-[18F]FPhe ([18F]10)–General Procedure 2 (GP 2)
3.5.7. Semi-Automated Synthesis of 18F-Labeled Products–General Procedure 3 (GP 3) (Figure 6)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of all compounds are available from the authors. |
Entry | Product | 18F-Recovery (%) | RCC (TLC) (%) | RCC (HPLC) (%) |
---|---|---|---|---|
1*a | 73 ± 3 (n = 3) | 94±3 (n = 3) | >99 (n = 3) | |
2**b | 94 ± 2 (n = 3) | – | 94 ± 5 (n = 3) | |
3**b | – | >99 (n = 3) | ||
4**b | 72 ± 9 (n = 3) | 89 ± 5 (n = 3) | ||
5**a,b | 87, 96 (n = 2) | 59, 68 (n = 2) | – | |
6**a,b | 89, 92 (n = 2) | 85, 86 (n = 2) | – | |
7**b | 92 (n = 1) | 62, 80 (n = 2) | 66 (n=1) | |
8**a,b | 86 ± 6 (n = 3) | 80, 98 (n = 2) | 99 |
Compound | Rf |
---|---|
[18F]2 | 0.4a |
[18F]4 | 0.3a |
[18F]5a | 0.5b |
[18F]5b | 0.4b |
[18F]6 | 0.4b |
[18F]7a | 0.5b |
[18F]7b | 0.5b |
HPLC-Method | HPLC-Conditions |
---|---|
A | X-Bridge C18 column 5 µm, 150 × 4.6 mm (Waters), 0–2 min: 5% MeCN, 2–13 min: 5→90% MeCN (2.0 mL/min), UV detection: 210 nm, injection loop: 20 µL |
B | Hydro-RP 4 µm 80 A 4.6 × 250 mm (Phenomenex), 2% EtOH (1.0 mL/min), UV detection: 210 nm, injection loop: 5 mL |
C | Hydro-RP 4 µm 80 A 4.6 × 250 mm (Phenomenex), 6% EtOH aq + 0.1% TFA (1.0 mL/min), UV detection: 210 nm, injection loop: 20 µL |
D | Crownpak (+) 5 μm 4.0 × 150 mm (Daicel Corporation), 0.025 M HClO4 (1.0 mL/min), UV detection: 210 nm, injection loop: 20 µL |
Compound | HPLC-Method | k’a |
---|---|---|
[18F]2 | A | 9.8 |
[18F]3 | A | 9.6 |
[18F]4 | A | 8.0 |
2-FPhe | B | 5.1 |
(R)-2-FPhe | C | 2.4 |
(S)-2-FPhe | C | 3.7 |
4-FPhe | B | 6.3 |
(R)-4-FPhe | C | 3.0 |
(S)-4-FPhe | C | 4.0 |
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Orlovskaya, V.V.; Modemann, D.J.; Kuznetsova, O.F.; Fedorova, O.S.; Urusova, E.A.; Kolks, N.; Neumaier, B.; Krasikova, R.N.; Zlatopolskiy, B.D. Alcohol-Supported Cu-Mediated 18F-Fluorination of Iodonium Salts under “Minimalist” Conditions. Molecules 2019, 24, 3197. https://doi.org/10.3390/molecules24173197
Orlovskaya VV, Modemann DJ, Kuznetsova OF, Fedorova OS, Urusova EA, Kolks N, Neumaier B, Krasikova RN, Zlatopolskiy BD. Alcohol-Supported Cu-Mediated 18F-Fluorination of Iodonium Salts under “Minimalist” Conditions. Molecules. 2019; 24(17):3197. https://doi.org/10.3390/molecules24173197
Chicago/Turabian StyleOrlovskaya, Victoriya V., Daniel J. Modemann, Olga F. Kuznetsova, Olga S. Fedorova, Elizaveta A. Urusova, Niklas Kolks, Bernd Neumaier, Raisa N. Krasikova, and Boris D. Zlatopolskiy. 2019. "Alcohol-Supported Cu-Mediated 18F-Fluorination of Iodonium Salts under “Minimalist” Conditions" Molecules 24, no. 17: 3197. https://doi.org/10.3390/molecules24173197
APA StyleOrlovskaya, V. V., Modemann, D. J., Kuznetsova, O. F., Fedorova, O. S., Urusova, E. A., Kolks, N., Neumaier, B., Krasikova, R. N., & Zlatopolskiy, B. D. (2019). Alcohol-Supported Cu-Mediated 18F-Fluorination of Iodonium Salts under “Minimalist” Conditions. Molecules, 24(17), 3197. https://doi.org/10.3390/molecules24173197