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