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Recent Advances in the Synthesis of Polyamine Derivatives and Their Applications
Article

Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of 18F-Labeled Radiotracers

by 1,*, 1,2 and 1,2,*
1
Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328 Dresden, Germany
2
Faculty of Chemistry and Food Chemistry, School of Science, Technische University Dresden, Mommsenstraße 4, 01069 Dresden, Germany
*
Authors to whom correspondence should be addressed.
Academic Editors: Anna Mìnarini and Michela Rosini
Molecules 2021, 26(22), 7012; https://doi.org/10.3390/molecules26227012
Received: 29 September 2021 / Revised: 12 November 2021 / Accepted: 17 November 2021 / Published: 20 November 2021
(This article belongs to the Special Issue Polyamine Drug Discovery)
Polyamines are highly attractive vectors for tumor targeting, particularly with regards to the development of radiolabeled probes for imaging by positron emission (PET) and single-photon emission computed tomography (SPECT). However, the synthesis of selectively functionalized derivatives remains challenging due to the presence of multiple amino groups of similar reactivity. In this work, we established a synthetic methodology for the selective mono-fluorobenz(o)ylation of various biogenic diamines and polyamines as lead compounds for the perspective development of substrate-based radiotracers for targeting polyamine-specific membrane transporters and enzymes such as transglutaminases. For this purpose, the polyamine scaffold was constructed by solid-phase synthesis of the corresponding oxopolyamines and subsequent reduction with BH3/THF. Primary and secondary amino groups were selectively protected using Dde and Boc as protecting groups, respectively, in orientation to previously reported procedures, which enabled the selective introduction of the reporter groups. For example, N1-FBz-spermidine, N4-FBz-spermidine, N8-FBz-spermidine, and N1-FBz-spermine and N4-FBz-spermine (FBz = 4-fluorobenzoyl) were obtained in good yields by this approach. The advantages and disadvantages of this synthetic approach are discussed in detail and its suitability for radiolabeling was demonstrated for the solid-phase synthesis of N1-[18F]FBz-cadaverine. View Full-Text
Keywords: amide bond reduction; reductive alkylation; 18F-labeling; prosthetic groups; site-selective chemical modification; transglutaminases; polyamine transport system; substrate-based probes; PET tracers; tumor targeting amide bond reduction; reductive alkylation; 18F-labeling; prosthetic groups; site-selective chemical modification; transglutaminases; polyamine transport system; substrate-based probes; PET tracers; tumor targeting
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MDPI and ACS Style

Wodtke, R.; Pietzsch, J.; Löser, R. Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of 18F-Labeled Radiotracers. Molecules 2021, 26, 7012. https://doi.org/10.3390/molecules26227012

AMA Style

Wodtke R, Pietzsch J, Löser R. Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of 18F-Labeled Radiotracers. Molecules. 2021; 26(22):7012. https://doi.org/10.3390/molecules26227012

Chicago/Turabian Style

Wodtke, Robert, Jens Pietzsch, and Reik Löser. 2021. "Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of 18F-Labeled Radiotracers" Molecules 26, no. 22: 7012. https://doi.org/10.3390/molecules26227012

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