Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers
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 ch...
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| Autores principales: | , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/85729e00646a4a43974744b344116256 |
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| Sumario: | 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 BH<sub>3</sub>/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, <i>N</i><sup>1</sup>-FBz-spermidine, <i>N</i><sup>4</sup>-FBz-spermidine, <i>N</i><sup>8</sup>-FBz-spermidine, and <i>N</i><sup>1</sup>-FBz-spermine and <i>N</i><sup>4</sup>-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 <i>N</i><sup>1</sup>-[<sup>18</sup>F]FBz-cadaverine. |
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