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Synlett 2018; 29(04): 410-414
DOI: 10.1055/s-0036-1591734
cluster
© Georg Thieme Verlag Stuttgart · New York

A Novel 18F-Labeling Method for the Synthesis of [18F]-Piperidine-Containing Ligands as Potential PET Radiotracers for σ Receptors

Gerardo X. Ortiz Jr.
a   Department of Chemistry, Duke University, Durham, NC 27708, USA   Email: qiu.wang@duke.edu
,
Kantapat Chansaenpak
b   Department of Radiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA   Email: zibo_li@med.unc.edu
c   National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Pathum Thani, 12120, Thailand
,
Mengzhe Wang
b   Department of Radiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA   Email: zibo_li@med.unc.edu
,
Xiaofen Ma
b   Department of Radiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA   Email: zibo_li@med.unc.edu
d   Department of Medical Imaging, Guangdong No. 2 Provincial People’s Hospital, Guangzhou City, Guangdong Province, P. R. of China
,
Hui Wang
b   Department of Radiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA   Email: zibo_li@med.unc.edu
,
Zibo Li*
b   Department of Radiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA   Email: zibo_li@med.unc.edu
,
Qiu Wang  *
a   Department of Chemistry, Duke University, Durham, NC 27708, USA   Email: qiu.wang@duke.edu
› Author AffiliationsWe acknowledge financial support to this project from Duke University, the Camille and Henry Dreyfus Foundation (QW), and the Department of Radiology and BRIC at UNC Chapel Hill.
Further Information

Publication History

Received: 22 September 2017

Accepted after revision: 08 November 2017

Publication Date:
19 December 2017 (online)

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Published as part of the Cluster Alkene Halofunctionalization

# These authors contributed equally to this work.

Abstract

We report a novel 18F-labeling method for the preparation of 18F-containing piperidine derivatives. This method is demonstrated on the design and synthesis of 18F-labeled potential PET radiotracers of σ receptors for initial biological evaluations.

1 Introduction

2 Design and Synthesis of Novel [19F]-3 and [ 19F]-3′

3 Radiosynthesis of Novel [18F]-3 and [18F]-3′

4 In vivo Uptake and Pharmacokinetics of [18F]-3 and [18F]-3′

5 Conclusion

Key words

amino fluorination - alkene - 18F-labeling - σ receptors - PET - radiotracer

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591734.
  • Supporting Information
 

  • References and Notes

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  • 6 See Supporting Information for details of the synthesis of [19F]-3 and [19F]-3′. [19F]-3: Rf = 0.56 (25% ethyl acetate–hexanes). 1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.8 Hz, 1 H), 7.61 (d, J = 8.2 Hz, 1 H), 7.35 (dd, J = 8.2, 7.1 Hz, 1 H), 7.21–7.15 (m, 3 H), 4.76 (dtt, J = 48.9, 8.6, 4.4 Hz, 1 H), 3.93 (s, 3 H), 3.14–3.02 (m, 2 H), 2.94–2.85 (m, 1 H), 2.42 (t, J = 7.0 Hz, 2 H), 2.24 (d, J = 11.2 Hz, 1 H), 2.21–2.13 (m, 1 H), 1.93–1.85 (m, 3 H), 1.74 (td, J = 13.8, 4.6 Hz, 1 H), 1.36 (td, J = 13.0, 9.0 Hz, 1 H), 1.02 (s, 6H). 13C NMR (125 MHz, CDCl3): δ = 157.2, 138.6, 135.1, 127.3, 126.2, 125.5, 125.4, 124.0, 124.0, 118.3, 106.6, 87.8 (d, 1J F–C = 169.9 Hz), 65.0, 58.5 (d, 2J F–C = 23.8 Hz), 57.4, 55.2, 43.4 (d, 2J F–C = 16.5 Hz), 31.8 (d, 3J F–C = 8.0 Hz), 30.4, 28.9, 28.2, 26.9. 19F NMR (376 MHz, CDCl3): δ = –182.0 to –182.9 (br m). FTIR (thin film): 2948, 1625, 1472, 1256, 1219, 1002 cm–1. ESI-HRMS: m/z calcd for C21H29FNO [M + H]+: 330.2228; found: 330.2228. [19F]-3′: Rf = 0.15 (50% ethyl acetate–hexanes). 1H NMR (500 MHz, CDCl3): δ = 7.98 (d, J = 8.8 Hz, 1 H), 7.60 (d, J = 8.2 Hz, 1 H), 7.35 (dd, J = 8.2, 7.0 Hz, 1 H), 7.21–7.14 (m, 3 H), 3.93 (s, 3 H), 3.05 (td, J = 7.6, 2.6 Hz, 2 H), 2.73–2.60 (br, m, 2 H), 2.45 (t, J = 7.6 Hz, 2 H), 2.20–2.11 (br, m, 1 H), 1.93 (quint, J = 7.6 Hz, 2 H), 1.93–1.77 (m, 3 H), 1.60–1.53 (m, 1 H), 1.36 (d, J = 21.6 Hz, 3 H), 0.98–0.85 (m, 1 H). 13C NMR (125 MHz, CDCl3, 60 °C): δ = 157.2, 138.5, 135.2, 127.4, 126.2, 125.6, 125.4, 123.9, 118.3, 106.7, 62.3 (d, 2 J F–C = 22.6 Hz), 58.1, 55.3, 53.3, 35.3 (d, 2 J F–C = 21.2 Hz), 30.7, 28.1 (d, 3 J F–C = 4.1 Hz), 25.2 (d, 2 J F–C = 24.6 Hz), 22.3 (note that the carbon peak for C–F can not be detected). 19F NMR (376 MHz, CDCl3) δ = –146.0 to –149.5 (br m). FTIR (thin film): 1530, 1349, 1288, 1266, 1133 cm–1. ESI-HRMS: m/z calcd for C20H27FNO [M + H]+: 316.2071; found: 316.2076.
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