The application of [18F]fluoride for radiofluorination of non-activated aromatic rings, such as alkyl-substituted benzene rings, phenols, and indoles, poses a significant challenge, and has slowed the development of fluorine-18 (t1/2 = 109.7 min) labeled amino acids for positron-emission tomography (PET). Imaging of amino acid transport and metabolism (e.g., with [18F]6-fluoro-L-DOPA, which remains a challenging synthetic target) has shown clinical utility for tumor characterization and for neurodegeneration associated with Parkinson's disease. We have recently discovered a method for one-step radiofluorination of non-activated arenes using [18F]fluoride and spirocyclic iodonium ylide-based precursors. This approach, which takes advantage of a highly optimized iodonium ylide auxiliary, was first applied to the synthesis of model compounds, such as 18F-phenyl ethers and 18F-indolines. We have since developed our approach for fluorinated derivatives of the amino acids phenylalanine, tyrosine, and tryptophan through a two-step radiosynthesis that involves radiofluorination with [18F]Et4NF in DMF at 120 �C for 10 min, followed by a deprotection step. Precursors for radiolabeling were prepared from protected iodoaryl amino acids, by a one-pot procedure that involved selective oxidation to form a diacetoxyiodoarene followed by conjugation with a spirocyclic auxiliary. The radiolabeling proceeded in synthetically useful yields (55% for a phenylalanine derivative relative to [18F]fluoride), with exquisite regioselectivity, and the products are easily purified using solid-phase extraction and/or semi-preparative HPLC. [18F]Fluorinated amino acids prepared in our laboratories will be applied for in vivo PET imaging studies.

[<sup>18</sup>F]Fluorinated amino acids prepared using spirocyclic iodonium ylides

248th National Meeting (2014)

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[18F]Fluorinated amino acids prepared using spirocyclic iodonium ylides

[¹⁸F]Fluorinated amino acids prepared using spirocyclic iodonium ylides