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@INPROCEEDINGS{Humpert:1026497,
      author       = {Humpert, Swen and Walter, Nils and Zlatopolskiy, Boris and
                      Neumaier, Bernd},
      title        = {4-{I}odophenyl-[18{F}]fluorosulfate as a versatile building
                      block for {P}d-catalyzed cross-coupling reactions},
      reportid     = {FZJ-2024-03441},
      year         = {2023},
      abstract     = {Introduction: Growing demand for positron emission
                      tomography(PET) probes necessitates access to a wide range
                      of 18F-labeled complexmolecules. However, many of such
                      compounds cannot be directlyradiofluorinated using existing
                      methods and should be labeledindirectly, using
                      18F-fluorinated building blocks. Recently a
                      novelradiolabeling method based on ultrafast sulfur 18F/19F
                      exchange (18FSuFEx)was published.[1,2] In this work, we
                      evaluated the suitability of4-iodophenyl-[18F]fluorosulfate
                      ([18F]1) prepared by this method as abuilding block for
                      indirect radiolabeling via different
                      Pd-catalyzedcross-coupling reactions.Methods: [18F]1 was
                      synthesized according to the optimized 18FSuFExlabeling
                      method[2], by eluting [18F]F– with BnEt3NCl (0.7 mL,2.2
                      mM) in MeOH, followed by evaporation of MeOH and the
                      additionof a solution of 1 in MeCN. Aliquots of the reaction
                      mixturewere eitherdirectly used for subsequent
                      cross-coupling reactions (generalprocedure 1 (GP1)) or
                      [18F]1 was first isolated by SPE as solution inEtOH or
                      dioxane. Aliquots of these solutions were used for
                      crosscoupling(GP2). Suzuki-Miyaura reactions with
                      4-biphenyl-boronicacid were performed according to GP1 using
                      solutions of the substrate(10 mM) and Pd(OAc)2 (5 mM) in
                      dioxane (100 μL of each), oraccording to GP2 by eluting
                      [18F]1 with 1.5 mL EtOH, diluting analiquot of this solution
                      (250 μL) with H2O (350 μL), and adding sat.NaHCO3 (50 μL)
                      followed by solutions of the substrate (10 mM) and Pd(OAc)2
                      (10 mM) in dioxane (50 μL of each). Stille cross coupling
                      with 4-biphenyltrimethylstannane was performed according to
                      GP2 byeluting [18F]1 with 1.0 mL dioxane and combining an
                      aliquot(250 μL) with solutions of the substrate (10 mM),
                      CuI (10 mM) andPd(OAc)2 (5 mM) in dioxane (100 μL of each).
                      S-Arylation of Boc-Cys-OMe as a representative substrate was
                      performed according to GP1using solutions of the substrate
                      (10 mM) and XantPhos Pd G3 (130 nM)in MeCN (100 μL of
                      each). Sonogashira reaction with propargyl aminewas
                      performed according to GP2 by eluting [18F]1 with 0.5 mL
                      dioxane,diluting an aliquot (100 μL) with EtOH (200 μL),
                      and adding solutionsof the substrate (42 mM, 100 μL), CuI
                      (10 mM, 50 μL), Pd-catalyst(5 mM, 100 μL) and DBU (10 mM,
                      100 μL) in dioxane. Radiochemicalconversions (RCCs) were
                      determined by HPLC.Results: [18F]1 (10–500 MBq) was
                      obtained from 1 (20 μg,66 nmol) in RCCs of $>85\%$ and
                      activity yields of $50–70\%$ within 20–25 min.
                      Subsequent Suzuki-Miyaura cross-coupling reactions
                      afforded1,1′:4,1″terphenyl-4-yl [18F]fluorosulfate
                      ([18F]2) in RCCs of $73–96\%after$ 20–30 min at 40 °C
                      (GP1) or $63–93\%$ after 25 min at r.t. (GP2). TheStille
                      reaction delivered [18F]2 in an RCC of 91 ± $1\%$ after 20
                      min at r.t. SArylationof Boc-Cys-OMe furnished
                      Boc-Cys(SPh-p-OSO2[18F]F)-OMe([18F]3) in 93 ± $3\%$ RCC
                      after 20 min at 40 °C. The Sonogashira reactiongave
                      4-(propargylamino)phenyl [18F]fluorosulfate ([18F]4) in a
                      RCC $of73\%$ after 15 min at 90 °C.Conclusion: [18F]1 is a
                      versatile building block for indirectradiolabeling via
                      different Pd-catalyzed cross coupling
                      reactions.Acknowledgements: This work was supported by the
                      GermanResearch Foundation (DFG grant ZL
                      65/4–1).References[1] Zheng Q., et al., J. Am. Chem. Soc.
                      2021, 142, 10, 3753–3763.[2] Walter N. et al., Eur. J.
                      Med. Chem. 2022, 237, 114383.},
      month         = {May},
      date          = {2023-05-22},
      organization  = {25th International Symposium on
                       Radiopharmaceutical Sciences, Honolulu
                       (USA), 22 May 2023 - 26 May 2023},
      subtyp        = {After Call},
      cin          = {INM-5},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/1026497},
}