{"id":{"repo_id":"tuebingen","oai_identifier":"oai:publikationen.uni-tuebingen.de:10900/49234"},"canonical_url":"https://search.dev.ndltd.org/etd/tuebingen/oai:publikationen.uni-tuebingen.de:10900/49234","repository":{"repo_id":"tuebingen","name":"Universität Tübingen","base_url":"https://publikationen.uni-tuebingen.de/oai/request"},"display":{"title":"Studies on the Nucleophilic Aromatic 18F-Fluorination- From Model Compounds to Aromatic Amino Acids","abstract":"The objective of this work was to develop a new strategy aiming at the syntheses of n.c.a. 18F-labeled aromatic amino acids via three steps, i.e. nucleophilic 18F-labeling, decarbonylation and hydrolysis. First, systematic investigations on nucleophilic aromatic 18F-fluorination was performed by using a variety of model compounds exhibiting different substitution patterns with both +M (-MeO or -Me) and -M substituents (leaving group (-LG) or -CHO). Secondly, the optimized decarbonylation condition was determined by decarbonylating the 18F-labeled model compounds. In overall synthesis, a proof-of-principle study on the synthesis of [18F]fluoro-p-tyrosine proved the three-step synthetic strategy to be suitable for syntheses of 18F-labeled aromatic amino acids. However, in the case of the precursor with low reactivity toward SNAr ([18F]fluoro-m-tyrosine and [18F]FDOPA), further optimization of the organic synthesis of precursors is in progress. In the last part, an automated synthesis of [18F]FDOPA over four steps (fluorination, reductive iodination, alkylation and hydrolysis), as described in the literature, was brought into routine application for the first time. 9064 ± 3076 MBq of [18F]FDOPA could be produced within 120 min of production time from EOB (n = 5). The radiochemical purity and enantiomeric purity were both 95 %. The specific activity was ca. 50 GBq/µmol at EOS.","abstract_html":"The objective of this work was to develop a new strategy aiming at the syntheses of n.c.a. 18F-labeled aromatic amino acids via three steps, i.e. nucleophilic 18F-labeling, decarbonylation and hydrolysis. First, systematic investigations on nucleophilic aromatic 18F-fluorination was performed by using a variety of model compounds exhibiting different substitution patterns with both +M (-MeO or -Me) and -M substituents (leaving group (-LG) or -CHO). Secondly, the optimized decarbonylation condition was determined by decarbonylating the 18F-labeled model compounds. In overall synthesis, a proof-of-principle study on the synthesis of [18F]fluoro-p-tyrosine proved the three-step synthetic strategy to be suitable for syntheses of 18F-labeled aromatic amino acids. However, in the case of the precursor with low reactivity toward SNAr ([18F]fluoro-m-tyrosine and [18F]FDOPA), further optimization of the organic synthesis of precursors is in progress. In the last part, an automated synthesis of [18F]FDOPA over four steps (fluorination, reductive iodination, alkylation and hydrolysis), as described in the literature, was brought into routine application for the first time. 9064 ± 3076 MBq of [18F]FDOPA could be produced within 120 min of production time from EOB (n = 5). The radiochemical purity and enantiomeric purity were both 95 %. The specific activity was ca. 50 GBq/µmol at EOS.","abstract_has_math":false,"creators":["Shen, Bin"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008","date_published":"2008","updated_at":"2026-08-21T22:21:56Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10900/49234"],"render_values":[{"text":"hdl:10900/49234","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"source_record":{"url":"https://publikationen.uni-tuebingen.de/oai/request?verb=GetRecord&metadataPrefix=mets&identifier=oai%3Apublikationen.uni-tuebingen.de%3A10900%2F49234","prefix":"mets"},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2008"]},{"key":"dc:type","label":"Dc Type","values":["PhDThesis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10900/49234"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["The objective of this work was to develop a new strategy aiming at the syntheses of n.c.a. 18F-labeled aromatic amino acids via three steps, i.e. nucleophilic 18F-labeling, decarbonylation and hydrolysis. First, systematic investigations on nucleophilic aromatic 18F-fluorination was performed by using a variety of model compounds exhibiting different substitution patterns with both +M (-MeO or -Me) and -M substituents (leaving group (-LG) or -CHO). Secondly, the optimized decarbonylation condition was determined by decarbonylating the 18F-labeled model compounds. In overall synthesis, a proof-of-principle study on the synthesis of [18F]fluoro-p-tyrosine proved the three-step synthetic strategy to be suitable for syntheses of 18F-labeled aromatic amino acids. However, in the case of the precursor with low reactivity toward SNAr ([18F]fluoro-m-tyrosine and [18F]FDOPA), further optimization of the organic synthesis of precursors is in progress. In the last part, an automated synthesis of [18F]FDOPA over four steps (fluorination, reductive iodination, alkylation and hydrolysis), as described in the literature, was brought into routine application for the first time. 9064 ± 3076 MBq of [18F]FDOPA could be produced within 120 min of production time from EOB (n = 5). The radiochemical purity and enantiomeric purity were both 95 %. The specific activity was ca. 50 GBq/µmol at EOS.","Das Ziel dieser Arbeit ist die Entwicklung einer neuen Strategie für die Synthese von n.c.a. 18F-markierten aromatischen Aminosäuren in drei Schritten, durch nukleophile 18F-Markierung, Decarbonylierung und Hydrolyse. Zunächst wurden systematische Untersuchungen zur nukleophilen aromatischen 18F-Fluorierung an verschiedenen Modellverbindungen durchgeführt, welche unterschiedliche Substitutionsmuster sowohl bei +M- (-MeO or -Me) als auch bei -M- Substituenten (Abgangsgruppe (-LG) oder -CHO) zeigten. Danach wurden für die 18F-markierten Modellverbindungen die Decarbonylierungsbedingungen optimiert. Eine proof-of-principle Untersuchung der gesamten [18F]Fluor-p-tyrosin-Synthese bewies, dass die Drei-Schritt-Strategie für die Synthese von 18F-markierten aromatischen Aminosäuren geeignet ist. Allerdings sind für die Vorläufer mit niedriger Reaktivität bezüglich der SNAr ([18F]Fluor-mtyrosin und [18F]FDOPA) weitere Optimierungen der organischen Vorläufersynthese in Arbeit. Zuletzt wurde eine vierstufige [18F]FDOPA-Synthese (Fluorierung, reduktive Iodierung, Alkylierung und Hydrolyse, wie in der Literatur beschrieben) erstmalig in eine automatisierte Routineanwendung umgesetzt. 9064 ± 3076 MBq [18F]FDOPA konnten bei einer Synthesezeit von 120 min (EOB, n=5) hergestellt werden. Die radiochemische und enantiomerische Reinheit lagen beide bei 95 %. Die spezifische Aktivität betrug ca. 50 GBq/µmol (EOS)."]},{"key":"dc:title","label":"Title","values":["Studies on the Nucleophilic Aromatic 18F-Fluorination- From Model Compounds to Aromatic Amino Acids"]}]}],"canonical_facts":{"dc:date.issued":["2008"],"dc:description.other":["The objective of this work was to develop a new strategy aiming at the syntheses of n.c.a. 18F-labeled aromatic amino acids via three steps, i.e. nucleophilic 18F-labeling, decarbonylation and hydrolysis. First, systematic investigations on nucleophilic aromatic 18F-fluorination was performed by using a variety of model compounds exhibiting different substitution patterns with both +M (-MeO or -Me) and -M substituents (leaving group (-LG) or -CHO). Secondly, the optimized decarbonylation condition was determined by decarbonylating the 18F-labeled model compounds. In overall synthesis, a proof-of-principle study on the synthesis of [18F]fluoro-p-tyrosine proved the three-step synthetic strategy to be suitable for syntheses of 18F-labeled aromatic amino acids. However, in the case of the precursor with low reactivity toward SNAr ([18F]fluoro-m-tyrosine and [18F]FDOPA), further optimization of the organic synthesis of precursors is in progress. In the last part, an automated synthesis of [18F]FDOPA over four steps (fluorination, reductive iodination, alkylation and hydrolysis), as described in the literature, was brought into routine application for the first time. 9064 ± 3076 MBq of [18F]FDOPA could be produced within 120 min of production time from EOB (n = 5). The radiochemical purity and enantiomeric purity were both 95 %. The specific activity was ca. 50 GBq/µmol at EOS.","Das Ziel dieser Arbeit ist die Entwicklung einer neuen Strategie für die Synthese von n.c.a. 18F-markierten aromatischen Aminosäuren in drei Schritten, durch nukleophile 18F-Markierung, Decarbonylierung und Hydrolyse. Zunächst wurden systematische Untersuchungen zur nukleophilen aromatischen 18F-Fluorierung an verschiedenen Modellverbindungen durchgeführt, welche unterschiedliche Substitutionsmuster sowohl bei +M- (-MeO or -Me) als auch bei -M- Substituenten (Abgangsgruppe (-LG) oder -CHO) zeigten. Danach wurden für die 18F-markierten Modellverbindungen die Decarbonylierungsbedingungen optimiert. Eine proof-of-principle Untersuchung der gesamten [18F]Fluor-p-tyrosin-Synthese bewies, dass die Drei-Schritt-Strategie für die Synthese von 18F-markierten aromatischen Aminosäuren geeignet ist. Allerdings sind für die Vorläufer mit niedriger Reaktivität bezüglich der SNAr ([18F]Fluor-mtyrosin und [18F]FDOPA) weitere Optimierungen der organischen Vorläufersynthese in Arbeit. Zuletzt wurde eine vierstufige [18F]FDOPA-Synthese (Fluorierung, reduktive Iodierung, Alkylierung und Hydrolyse, wie in der Literatur beschrieben) erstmalig in eine automatisierte Routineanwendung umgesetzt. 9064 ± 3076 MBq [18F]FDOPA konnten bei einer Synthesezeit von 120 min (EOB, n=5) hergestellt werden. Die radiochemische und enantiomerische Reinheit lagen beide bei 95 %. Die spezifische Aktivität betrug ca. 50 GBq/µmol (EOS)."],"dc:identifier":["hdl:10900/49234"],"dc:title":["Studies on the Nucleophilic Aromatic 18F-Fluorination- From Model Compounds to Aromatic Amino Acids"],"dc:type":["PhDThesis"]},"updated_at":"2026-08-21T22:21:56Z"}