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@INPROCEEDINGS{Cavani:825301,
      author       = {Cavani, Melanie and Bier, Dirk and Coenen, Heinrich Hubert},
      title        = {{N}ew strategy of a two-step radiosynthesis of
                      [{F}-18]fluoropyridine-based maleimide-containing prosthetic
                      groups for labelling of peptides and proteins},
      reportid     = {FZJ-2016-07765},
      year         = {2015},
      abstract     = {Objectives The use of thiol-reactive groups allows the
                      introduction of fluorine-18 in a peptide or protein with
                      cysteine residues, and different radiofluorinated
                      maleimide-containing prosthetic groups have been described
                      in the literature. All compounds were, however, prepared by
                      a two- or three-step synthesis with an overall reaction time
                      of at least 70 minutes. The aim of this work was to improve
                      the radiosynthesis of maleimide-containing compounds with
                      reduced reaction steps by using a new synthetic route via
                      protection of the maleimide function. This was first done
                      here with the example of
                      1-[3-(2-[18F]fluoropyridin-3-oxy)propyl]pyrrol-2,5-dione
                      ([18F]FPyME) which is usually prepared in three steps [1].
                      Methods The first step for the preparation of the precursor
                      was a Williamson reaction to form the ether from
                      3-hydroxy-2-nitropyridine with 1,3-dibromopropane. In a
                      parallel process maleimide was protected with
                      2,5-dimethylfurane via a Diels-Alder-reaction. These two
                      products were combined by N-alkylation to form the
                      precursor. The radiosynthesis includes the introduction of
                      fluorine-18 by nucleophilic substitution of the nitro group
                      followed by deprotection of the maleimide function (see fig.
                      1). The reaction steps were optimized with regard to
                      temperature, time and solvents. Results The optimal
                      conditions for the n.c.a. radiofluorination were identified
                      at a temperature of 80 °C in DMSO and a reaction time of 5
                      minutes, resulting in a radiochemical yield of about 29 ± 3
                      $\%.$ At higher temperatures the deprotection of the
                      precursor and the labelled compound come to the fore and
                      thereby the decomposition of the unprotected maleimide
                      occurs due to the basic reaction conditions. The
                      deprotection step was quantitatively carried out within 15
                      minutes. [18F]FPyME was isolated by HPLC to provide the pure
                      prosthetic group which was directly used for effective
                      peptide labelling. The overall synthesis time was about 60
                      minutes and the overall radiochemical yield was about 20
                      $\%.$ Conclusions The described synthetic route provides the
                      possibility to gain a variety of further
                      [18F]fluoropyridine-based maleimide-containing compounds in
                      two steps only. In addition, this method offers to be
                      performed as one-pot synthesis. Acknowledgements References
                      [1] de Bruin B. et al. (2006) Bioconjugate Chem., 16,
                      406-420.},
      month         = {May},
      date          = {2015-05-26},
      organization  = {21st International Symposium on
                       Radiopharmaceutical Sciences, Columbia
                       (USA), 26 May 2015 - 31 May 2015},
      subtyp        = {Plenary/Keynote},
      cin          = {INM-5},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)24},
      url          = {https://juser.fz-juelich.de/record/825301},
}