Selective fluorination of m-tyrosine by OF2

Babak Behnam Azad, Rezwan Ashique, Raman Chirakal, Gary J. Schrobilgen

Research output: Contribution to journalArticle

Abstract

Fluorine-18 labeled aromatic amino acids are routinely used as tracers in positron emission tomography (PET) to study in vivo metabolic processes. The most versatile method for the production of such radiotracers is electrophilic fluorination of the aromatic amino acid with [18F]F2, which is most commonly produced by the gas-phase nuclear reaction 18O(p, n)18F. Although [18F]F2 is the major product, considerable amounts of [18F]OF2 (up to 20%) are also produced. Electrophilic fluorination reactions of l-phenylalanine, 3-nitro-l-tyrosine, 4-nitro-dl-phenylalanine, 3,4-dihydroxyphenyl-l-alanine (l-DOPA), 3-O-methyl-l-DOPA, 3,4-dimethoxy-l-phenylalanine, p-tyrosine and o-tyrosine in H2O and of m-tyrosine in anhydrous HF (aHF), CF3SO3H, CF3COOH, CH3COOH, HCOOH and H2O using OF2 were investigated. Although F2 is an efficient fluorinating agent in aHF, electrophilic fluorination reactions using OF2 were shown to be most efficient in less acidic media such as H2O. In addition, and contrary to reports that OF2 and F2 have similar reactivities, m-tyrosine was the only aromatic system studied that was fluorinated by OF2 and this was optimum in H2O for the fluorinated m-tyrosine isomers (total yield, 4.35 ± 0.04%). The presence of [18F]OF2 byproduct has no significant impact on the fluorination of aromatic amino acids investigated in this study and the subsequent production of their corresponding 18F-labeled radiotracers for patient use.

Original languageEnglish (US)
Pages (from-to)22-27
Number of pages6
JournalJournal of Fluorine Chemistry
Volume129
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Fingerprint

Fluorination
fluorination
tyrosine
Halogenation
Aromatic Amino Acids
amino acid
Phenylalanine
Tyrosine
phenylalanine
amino acids
fluorine
Positron emission tomography
tomography
Nuclear reactions
Fluorine
tracer
Isomers
Alanine
Positron-Emission Tomography
Byproducts

Keywords

  • Electrophilic fluorination
  • Fluorine-18
  • Fluoro-m-tyrosine
  • Oxygen difluoride
  • PET

ASJC Scopus subject areas

  • Environmental Chemistry
  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Selective fluorination of m-tyrosine by OF2. / Behnam Azad, Babak; Ashique, Rezwan; Chirakal, Raman; Schrobilgen, Gary J.

In: Journal of Fluorine Chemistry, Vol. 129, No. 1, 01.2008, p. 22-27.

Research output: Contribution to journalArticle

Behnam Azad, Babak ; Ashique, Rezwan ; Chirakal, Raman ; Schrobilgen, Gary J. / Selective fluorination of m-tyrosine by OF2. In: Journal of Fluorine Chemistry. 2008 ; Vol. 129, No. 1. pp. 22-27.
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AB - Fluorine-18 labeled aromatic amino acids are routinely used as tracers in positron emission tomography (PET) to study in vivo metabolic processes. The most versatile method for the production of such radiotracers is electrophilic fluorination of the aromatic amino acid with [18F]F2, which is most commonly produced by the gas-phase nuclear reaction 18O(p, n)18F. Although [18F]F2 is the major product, considerable amounts of [18F]OF2 (up to 20%) are also produced. Electrophilic fluorination reactions of l-phenylalanine, 3-nitro-l-tyrosine, 4-nitro-dl-phenylalanine, 3,4-dihydroxyphenyl-l-alanine (l-DOPA), 3-O-methyl-l-DOPA, 3,4-dimethoxy-l-phenylalanine, p-tyrosine and o-tyrosine in H2O and of m-tyrosine in anhydrous HF (aHF), CF3SO3H, CF3COOH, CH3COOH, HCOOH and H2O using OF2 were investigated. Although F2 is an efficient fluorinating agent in aHF, electrophilic fluorination reactions using OF2 were shown to be most efficient in less acidic media such as H2O. In addition, and contrary to reports that OF2 and F2 have similar reactivities, m-tyrosine was the only aromatic system studied that was fluorinated by OF2 and this was optimum in H2O for the fluorinated m-tyrosine isomers (total yield, 4.35 ± 0.04%). The presence of [18F]OF2 byproduct has no significant impact on the fluorination of aromatic amino acids investigated in this study and the subsequent production of their corresponding 18F-labeled radiotracers for patient use.

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KW - Oxygen difluoride

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