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@PHDTHESIS{Wagner:62451,
      author       = {Wagner, Franziska M.},
      title        = {{Z}ur {S}ynthese radiofluorierter aromatischer
                      {A}minosäuren mittels {I}sotopenaustausch am {B}eispiel von
                      6-[$^{18}${F}]{F}luor-{L}-{DOPA}},
      volume       = {4273},
      issn         = {0944-2952},
      school       = {Univ. Köln},
      type         = {Dr. (Univ.)},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
      reportid     = {PreJuSER-62451, Juel-4273},
      series       = {Berichte des Forschungszentrums Jülich},
      pages        = {III, 188 p.},
      year         = {2008},
      note         = {Record converted from VDB: 12.11.2012; Köln, Univ., Diss.,
                      2008},
      abstract     = {In nuclear medical diagnosis,
                      6-[$^{18}$F]fluoro-L-3,4-dihydroxyphenylalanine
                      (6-[$^{18}$F]fluoro-LDOPA), an analogue of L-DOPA, is one of
                      the few established radiopharmaceuticals used for the in
                      vivo investigation of the presynaptic dopaminergic
                      metabolism and of some kind of tumours via Positron Emission
                      Tomography (PET). The presently used method of preparation
                      of the radiotracer by electrophilic labelling is limited to
                      low amounts of activity at high costs. Known nucleophilic
                      syntheses, however, result either in insufficient
                      enantiomeric purity or the known multi-step syntheses are
                      hard to automate, due to their complexity. During this work
                      a novel, easy to automate alternative for the preparation of
                      6-[$^{18}$F]fluoro-L-DOPA, was developed and evaluated,
                      using a direct nucleophilic $^{18}$F-fluorination of a
                      protected amino acid derivative. The resulting product has a
                      very high enantiomeric purity. At first, the general
                      suitability of the (S)-BOC-BMI-derivatives for the synthesis
                      of $^{18}$F-labelled amino acids, used in this work, was
                      investigated using a less complex precursor, which resulted
                      in the amino acid 6-[$^{18}$F]fluoro-L-m-tyrosin via acidic
                      hydrolysis. The preparation of a useful precursor for the
                      nucleophilic $^{18}$F-isotope substitution, namely the
                      (2S,5S)-tert.-butyl-5-(2-fluoro-5-formylbenzyl)-2-tert.-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate,
                      was investigated in three general different ways. At first
                      it was tried to obtain this product via formylation after
                      coupling with the BOC-BMI, secondly via a,b-dehydro amino
                      acid derivatives and finally via a systematic multi-step
                      synthesis. Only the last mentioned way resulted in a
                      precursor with sufficient purity that could be labelled. The
                      radiochemical yield of the isotopic exchange was about 60
                      \%. In the next step, the presented concept was modified to
                      synthesize a precursor for the preparation of
                      6-[$^{18}$F]fluoro-L-DOPA. Only a combination of the
                      protecting groups benzyl and THP resulted in the useful
                      precursor
                      (2S,5S)-tert.-butyl-5-(4-benzyloxy-2-fluoro-5-formylbenzyl)-2-tert.-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate.
                      By optimisation of the isotopic exchange with [18F]fluoride
                      on this precursor a radiochemical yield of about 50 \% was
                      achieved. After a three step synthesis including the
                      labelling, a Baeyer-Villiger-oxidation using mCPBA and a
                      hydrolysis using HBr, c.a. 6-[$^{18}$F]fluoro-L-DOPA was
                      isolated containing more than 99 \% of the desired L-isomer.
                      The complete preparation and isolation of c.a.
                      6-[$^{18}$F]fluoro-L-DOPA, using optimised conditions,
                      resulted in a decay corrected yield of about 22 \% after a
                      synthesis time of 105 minutes. Thus the presented synthesis
                      of 6-[$^{18}$F]fluoro-L-DOPA is not only more efficient than
                      the known methods of preparation, but is furthermore fully
                      automatable.},
      cin          = {INB-4},
      cid          = {I:(DE-Juel1)VDB807},
      pnm          = {Funktion und Dysfunktion des Nervensystems},
      pid          = {G:(DE-Juel1)FUEK409},
      typ          = {PUB:(DE-HGF)11 / PUB:(DE-HGF)3},
      url          = {https://juser.fz-juelich.de/record/62451},
}