An approach to the asymmetric synthesis of l-6-[18F]fluorodopa via NCA nucleophilic fluorination

In Vivo Biodistribution of No-Carrier-Added 6-18F-Fluoro-3,4-Dihydroxy-l-Phenylalanine (18F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added 18F-DOPA, Prepared by Conventional Electrophilic Substitution

“…One the authors of the manuscript, Kiel D. Neumann, is an employee of Ground Fluor Pharmaceuticals, Inc., Lincoln, Nebraska, which gave nonfinancial support by providing diaryliodonium salt precursor materials for the nucleophilic synthesis of both 18 F-DOPA and 6-18 F-fluorodopamine. Another author, Stephen G. DiMagno, holds a patent for the nucleophilic fluorination of aromatic ring systems, which includes the nucleophilic synthesis of 18 F-DOPA via a diaryliodonium salt precursor (US Patent 8,604,213 B2, Dec. 10,2013). No other potential conflict of interest relevant to this article was reported.…”

“…The difficulty of generating and handling 18 F 2 and the large amount of carrier 19 F-DOPA that is generated during the electrophilic process are major disadvantages, which have led to the development of various nucleophilic substitution protocols for the production of 18 F-DOPA using no-carrier-added fluoride (9)(10)(11)(12)(13). DiMagno has recently developed a fully elaborated diaryliodonium salt precursor, which allows for the facile production of no-carrier-added 18 F-DOPA via radiofluorination, followed by deprotection (14).…”

Tracers for metabolic imaging of brain and heart

“…From the lSFlabelled amino acids only L-4-~SF-fluorophenylalanine (15) (Bodsch et al 1988) and 2FTyr (14) ) are incorporated into proteins. Alternative, multi-step, nucleophilic procedures do not presently lead to higher overall yields (Lemaire et al 1987(Lemaire et al , 1991a. 4), comparable to L-l-14C-tyrosine and other natural amino acids.…”

Methods for 11C‐ and 18F‐labelling of amino acids and derivatives for positron emission tomography imaging

“…In later attempts, the 18 F‐labelled aldehyde was first converted into [ 18 F]fluorobenzyl bromide or iodide derivatives that were coupled with the chiral amino acid auxiliaries (1R,2R,5R)‐[(+)‐2‐hydroxypinanyl‐3‐idene]glycine tert ‐butyl ester, to obtain 6‐[ 18 F]fluoro‐ l ‐dopa, or (S)‐(−)‐1‐boc‐2‐tert.‐butyl‐3‐methyl‐4‐imidazolidinone, to obtain 6‐[ 18 F]fluoro‐ l ‐dopa, α‐methylated derivatives, and 4‐chloro‐2‐[ 18 F]fluoro‐α‐methyl‐ l ‐phenylalanine . This latter method gave a higher enantiomeric excess of the aromatic amino acids.…”