Fluorine for Hydroxy Substitution in Biogenic Amines: Asymmetric Synthesis and Biological Evaluation of Fluorine-18-Labeled .beta.-Fluorophenylalkylamines as Model Systems

Abstract

This work explores the biomimetic potential of [18F]fluorine for hydroxy substitution in beta-phenethanolamines as a possible strategy for developing radiotracers for in vivo imaging. Stereospecific syntheses of the two model compounds (1R,2S)-1-[18F]fluoro-1-deoxyephedrine ([18F]FDE) and (1S,2S)-1-[18F]fluoro-1-deoxypseudoephedrine ([18F]FDP) were achieved in high radiochemical yield (62%, decay corrected) and high specific activity (> 2500 Ci/mmol) by reaction of [18F]fluoride ion with the appropriate chiral cyclic sulfamidate precursor. Both tracers exhibited good stability toward metabolic defluorination in vivo. High, homogeneous brain uptake (approximately 8% of injected dose) was observed after intravenous injection in mice similar to that reported for the structurally related analog [11C]methamphetamine. The 1R,2S isomer (FDE) showed a 3-fold higher concentration of radioactivity in whole brain as compared to the 1S,2S isomer (FDP). These results suggest possible employment of this strategy for chiral radiolabeling of biologically important phenethanolamines and catecholamines.

Amphiphilic Polyfluorinated Amino Ethers from Cyclic Sulfamidates

“…The ring opening of versatile cyclic sulfamidates by means of fluorinated nucleophiles was reported in the literature that include formation of C–F, ,− C–R F , and C–SCF 3 bonds, but the construction of C–OR F is still a rare disconnection . We have filled this gap by investigating the regioselective ring opening of 1,2- and 1,3-cyclic sulfamidates with diverse polyfluorinated alkoxides.…”

Methods to Enhance the Metabolic Stability of Peptide-Based PET Radiopharmaceuticals

“…Ensuring that the radiometal is not lost from the radiopharmaceutical in vivo is of critical concern when developing these drugs as the free radiometal may exhibit high toxicity and cause significant damage to the body [25]. In the case of fluorine-18 labeled radiopharmaceuticals, in vivo radiodefluorination results in the release of free [ 18 F]fluoride ions that can readily accumulate into the calcium-rich fluorophilic bones of the body [26]. Radiodefluorination and in vivo metabolism of [ 18 F]radiopharmaceuticals also present major challenges to imaging studies as non-specific uptake of free [ 18 F]fluoride ions and [ 18 F]metabolites can lead to a degradation of the signal to noise ratio [27].…”

Regioselective and Stereodivergent Synthesis of Enantiomerically Pure Vic-Diamines from Chiral β-Amino Alcohols with 2-Pyridyl and 6-(2,2′-Bipyridyl) Moieties

“…The synthesis consisted of three steps (Scheme 3). Firstly oxathiazolidines 15 and 16 were obtained by reaction of appropriate amino alcohol 1 and 5 with thionyl chloride [39]. Then, they were oxidized to the cyclic sulfamidates 17 and 18 using sodium meta-periodate and a catalytic amount of ruthenium trichloride in acetonitrile.…”

“…The synthesis of S,S-dioxides was performed according to a modified literature procedure [39,40]. To a solution of amino alcohol 1 or 5 (1 mmol) and triethylamine (3 mmol, 0.42 mL) in dry dichloromethane (3.5 mL) was added a solution of thionyl chloride (0.8 mmol, 58 µL) in dry dichloromethane (0.25 mL) at −78 • C over 20 min.…”