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@INPROCEEDINGS{Weiss:825274,
      author       = {Weiss, Philipp and Castillo, Johnny and Ermert, Johannes
                      and Coenen, Heinrich Hubert},
      title        = {{S}ynthesis of {L}-4-[18{F}]fluorotryptophan starting from
                      isotopic exchange},
      reportid     = {FZJ-2016-07745},
      year         = {2015},
      abstract     = {Objectives: Radiofluorinated tryptophan is an interesting
                      tracer candidate. Tryptophan is the precursor of serotonin
                      which is important for a broad variety of neurological
                      regulation processes and is also involved in many
                      neurological diseases, such as depression. Further, it was
                      recently pointed out that some tumors have highly elevated
                      tryptophan consumption to overcome immune barriers [1].
                      Until now tryptophan has been labelled either in a very
                      complex radiosynthesis by a Schiemann reaction on
                      diethylformamido malonates giving low radiochemical yields
                      (RCY) or by secondary groups [2]. The aim of this work was
                      to find a suitable route for the radiosynthesis of
                      L-4-[18F]fluorotryptophan, starting from isotopic exchange.
                      Tests with bacteria showed no toxicity of the title compound
                      [4].Methods: Starting from 4-fluoroindole, the precursor for
                      the radiosynthesis of 4-fluorotryptophan was prepared in a
                      linear 11 step synthesis with an overall yield of 8 $\%,$
                      following a modified route to the one described by Konas et
                      al. [3]. The radiosynthesis was designed and carried out in
                      three steps: isotopic exchange, reductive decarbonylation
                      and hydrolysis of protecting groups. All reactions were
                      optimized regarding time, solvents, temperature and
                      concentration of reagents. Results: It was found that the
                      optimum temperature for the radiofluorination is 80 °C,
                      yielding a RCY of 51 $\%.$ Above 90 °C almost complete
                      decomposition of the starting material occurred. For the
                      reductive decarbonylation the best results were obtained
                      using benzonitrile as solvent and 3 equivalents of
                      Wilkinson’s catalyst. The reaction was performed under
                      either conventional or microwave heating giving RCYs of
                      about 78 $\%.$ The final hydrolysis gave yields of about 34
                      $\%.$ Conclusion: The whole radiosynthesis of
                      L-4-[18F]fluorotryptophan was achieved in about 115 min with
                      an overall RCY of ca. 13 $\%,$ a molar activity of > 70
                      MBq/mmol and an enantiomeric purity of > 99 $\%.$ This new
                      radiotracer is now available for preclinical evaluation
                      studies.References: [1] Prendergast G.C., (2011) Nature,
                      478, 192-194. [2] Ermert J., (2013) J. Labelled Compds
                      Radiopharm., 56, 225-236. [3] Konas D.W. et al., (2012)
                      Synth. Comm., 42, 144-152. [4] Bacher J.M., (2001) J.
                      Bacteriol., 183, 5414-5425.},
      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          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/825274},
}