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:	Robert Wodtke, Jens Pietzsch, Reik Löser
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	amide bond reduction reductive alkylation <sup>18</sup>F-labeling prosthetic groups site-selective chemical modification transglutaminases Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/85729e00646a4a43974744b344116256
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spelling	oai:doaj.org-article:85729e00646a4a43974744b3441162562021-11-25T18:29:10ZSolid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers10.3390/molecules262270121420-3049https://doaj.org/article/85729e00646a4a43974744b3441162562021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/7012https://doaj.org/toc/1420-3049Polyamines 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.Robert WodtkeJens PietzschReik LöserMDPI AGarticleamide bond reductionreductive alkylation<sup>18</sup>F-labelingprosthetic groupssite-selective chemical modificationtransglutaminasesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 7012, p 7012 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amide bond reduction reductive alkylation <sup>18</sup>F-labeling prosthetic groups site-selective chemical modification transglutaminases Organic chemistry QD241-441
spellingShingle	amide bond reduction reductive alkylation <sup>18</sup>F-labeling prosthetic groups site-selective chemical modification transglutaminases Organic chemistry QD241-441 Robert Wodtke Jens Pietzsch Reik Löser Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers
description	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.
format	article
author	Robert Wodtke Jens Pietzsch Reik Löser
author_facet	Robert Wodtke Jens Pietzsch Reik Löser
author_sort	Robert Wodtke
title	Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers
title_short	Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers
title_full	Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers
title_fullStr	Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers
title_full_unstemmed	Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers
title_sort	solid-phase synthesis of selectively mono-fluorobenz(o)ylated polyamines as a basis for the development of <sup>18</sup>f-labeled radiotracers
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/85729e00646a4a43974744b344116256
work_keys_str_mv	AT robertwodtke solidphasesynthesisofselectivelymonofluorobenzoylatedpolyaminesasabasisforthedevelopmentofsup18supflabeledradiotracers AT jenspietzsch solidphasesynthesisofselectivelymonofluorobenzoylatedpolyaminesasabasisforthedevelopmentofsup18supflabeledradiotracers AT reikloser solidphasesynthesisofselectivelymonofluorobenzoylatedpolyaminesasabasisforthedevelopmentofsup18supflabeledradiotracers
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Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of <sup>18</sup>F-Labeled Radiotracers

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