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Development of new Fluorination Methods Directed to Fluorine-18 Labelling
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.ORCID-id: 0000-0003-4299-8860
2019 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

This thesis deals with the development of new fluorination reactions and their application to fluorine-18 labelling. Fluorine-18 labelled compounds are employed as tracers in Positron Emission Tomography (PET), which is a powerful non-invasive imaging method in medical diagnostics.

The first part of this thesis focuses on the development of a late-stage halogen exchange-based fluorination method for the synthesis of trifluoromethylated molecules. The first project in this area relies on the application of a copper(I)-based fluorinating reagent to furnish trifluoroacetates, trifluorotoluenes and trifluoroacetamides. The second project involves the translation of this methodology into the fluorine-18 labelling of tertiary and secondary trifluoroacetamides. The targeted substrates were labelled in high radiochemical yield and high molar activity using [18F]Bu4NF as fluorine source in the presence of an organic activator.

In the second part, the development of electrophilic fluorination reactions using a hypervalent iodine-based reagent is discussed. The first project in this area addresses the development of an electrophilic fluorine-18 fluorination reagent: [18F]fluoro-benziodoxole. The utility of this reagent was demonstrated in the labelling of [18F]fluoro-benzoxazepines. In the second project, the same [18F]fluoro-benziodoxole reagent was used in the rhodium-mediated synthesis of α-[18F]fluoroethers. High molar activities were obtained in these electrophilic labelling processes. In the third project, the fluorine-19 analog fluoro-benziodoxole was used in the palladium-catalyzed iodofluorination of allyl benzenes, styrenes and cycloalkenes. Both iodine and fluorine atoms in the product arise from the same reagent.

Ort, förlag, år, upplaga, sidor
Sockholm: Department of Organic Chemistry, Stockholm University , 2019. , s. 73
Nyckelord [en]
fluorine, fluorine-18, late-stage, labelling, nucleophilic, electrophilic, fluorination, positron emision tomography, PET, hypervalent iodine, benziodoxole, metal-free, DBU, copper, palladium, rhodium, carbene
Nationell ämneskategori
Organisk kemi
Forskningsämne
organisk kemi
Identifikatorer
URN: urn:nbn:se:su:diva-175601ISBN: 978-91-7797-919-7 (tryckt)ISBN: 978-91-7797-920-3 (digital)OAI: oai:DiVA.org:su-175601DiVA, id: diva2:1368043
Disputation
2020-01-20, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 15:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2019-12-16 Skapad: 2019-11-05 Senast uppdaterad: 2022-02-26Bibliografiskt granskad
Delarbeten
1. Synthesis of trifluoromethyl moieties by late-stage copper (I) mediated nucleophilic fluorination
Öppna denna publikation i ny flik eller fönster >>Synthesis of trifluoromethyl moieties by late-stage copper (I) mediated nucleophilic fluorination
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2017 (Engelska)Ingår i: Journal of fluorine chemistry, ISSN 0022-1139, E-ISSN 1873-3328, Vol. 194, s. 51-57Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The nucleophilic fluorination of bromodifluoromethyl derivatives mediated by the complex (PPh3)(3)CuF is described. Under the reaction conditions, different trifluoroacetates, trifluorolcetones, trifluoroarenes and trifluoroacetamides were obtained in good yields.

Nyckelord
Nucleophilic fluorination, Copper, Trifluoroacetate, Trifluoromethylarene, Trifluoroacetamide
Nationell ämneskategori
Organisk kemi
Forskningsämne
organisk kemi
Identifikatorer
urn:nbn:se:su:diva-141365 (URN)10.1016/j.jfluchem.2016.12.017 (DOI)000393938200007 ()
Tillgänglig från: 2017-05-02 Skapad: 2017-05-02 Senast uppdaterad: 2022-02-28Bibliografiskt granskad
2. Efficient DBU accelerated synthesis of F-18-labelled trifluoroacetamides
Öppna denna publikation i ny flik eller fönster >>Efficient DBU accelerated synthesis of F-18-labelled trifluoroacetamides
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2016 (Engelska)Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 52, nr 97, s. 13963-13966Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Nucleophilic F-18-fluorination of bromodifluoromethyl derivatives was performed using [F-18] Bu4NF in the presence of DBU(1,8-diazabicyclo[5.4.0]undec-7-ene). This novel procedure provided a diverse set of [F-18] trifluoroacetamides in good to excellent radiochemical conversions. A mechanism where DBU acts as organomediator in this transformation is proposed.

Nationell ämneskategori
Organisk kemi
Forskningsämne
organisk kemi
Identifikatorer
urn:nbn:se:su:diva-139349 (URN)10.1039/c6cc08535k (DOI)000390436700005 ()27844069 (PubMedID)
Forskningsfinansiär
VetenskapsrådetKnut och Alice Wallenbergs Stiftelse
Tillgänglig från: 2017-02-07 Skapad: 2017-02-06 Senast uppdaterad: 2022-03-23Bibliografiskt granskad
3. [F-18]fluoro-benziodoxole: a no-carrier-added electrophilic fluorinating reagent. Rapid, simple radiosynthesis, purification and application for fluorine-18 labelling
Öppna denna publikation i ny flik eller fönster >>[F-18]fluoro-benziodoxole: a no-carrier-added electrophilic fluorinating reagent. Rapid, simple radiosynthesis, purification and application for fluorine-18 labelling
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2018 (Engelska)Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 54, nr 34, s. 4286-4289Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Operationally simple radiosynthesis and purification of [F-18]fluoro-benziodoxole was developed starting from a cyclotron produced [F-18]F- precursor, [F-18]TBAF, and tosyl-benziodoxole. The synthetic utility of [F-18]fluoro-benziodoxole was demonstrated by electrophilic fluorocyclization of o-styrilamides proceeding with high RCC (typically 50-90%) and high molar activity (up to 396 GBq mol(-1)).

Nationell ämneskategori
Organisk kemi
Forskningsämne
organisk kemi
Identifikatorer
urn:nbn:se:su:diva-156663 (URN)10.1039/c8cc00526e (DOI)000430935200013 ()29632936 (PubMedID)
Tillgänglig från: 2018-06-04 Skapad: 2018-06-04 Senast uppdaterad: 2022-03-23Bibliografiskt granskad
4. Rhodium-mediated 18F-oxyfluorination ofdiazoketones using a fluorine-18-containing hypervalent iodine reagent
Öppna denna publikation i ny flik eller fönster >>Rhodium-mediated 18F-oxyfluorination ofdiazoketones using a fluorine-18-containing hypervalent iodine reagent
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2019 (Engelska)Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 55, nr 89, s. 13358-13361Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Geminal 18F-oxyfluorination of diazoketones was performed in the presence of rhodium mediators. The reactions were performed using a hypervalent iodine-based [18F]fluoro-benziodoxole reagent. By this methodology various α-[18F]fluoro ethers were obtained in high radiochemical yield (up to 98%) and molar activity (216 GBq μmol-1).

Nyckelord
fluorine-18, electrophilic, hypervalent iodine, PET, rhodium, diazo compound
Nationell ämneskategori
Organisk kemi
Forskningsämne
organisk kemi
Identifikatorer
urn:nbn:se:su:diva-175600 (URN)10.1039/c9cc06905d (DOI)000496175900002 ()
Forskningsfinansiär
VetenskapsrådetKnut och Alice Wallenbergs Stiftelse, 2018.0066
Tillgänglig från: 2019-11-05 Skapad: 2019-11-05 Senast uppdaterad: 2022-03-23Bibliografiskt granskad
5. Palladium-Catalyzed lodofluorination of Alkenes Using Fluorolodoxole Reagent
Öppna denna publikation i ny flik eller fönster >>Palladium-Catalyzed lodofluorination of Alkenes Using Fluorolodoxole Reagent
2016 (Engelska)Ingår i: ACS Catalysis, E-ISSN 2155-5435, Vol. 6, nr 1, s. 447-450Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The application of an air- and moisture-stable fluoroiodane reagent was investigated in the palladium-catalyzed iodofluorination reaction of alkenes. Both the iodo and fluoro substituents arise from the fluoroiodane reagent. In the case of certain palladium catalysts, the alkene substrates undergo allylic rearrangement prior to the iodofluorination process. The reaction is faster for electron-rich alkenes than for electron-deficient ones.

Nyckelord
fluorination, hypervalent iodines, iodofluorination, palladium catalysis, alkenes, difunctionalization
Nationell ämneskategori
Organisk kemi
Forskningsämne
organisk kemi
Identifikatorer
urn:nbn:se:su:diva-126379 (URN)10.1021/acscatal.5b02022 (DOI)000367706800049 ()
Forskningsfinansiär
VetenskapsrådetKnut och Alice Wallenbergs Stiftelse
Tillgänglig från: 2016-02-12 Skapad: 2016-02-01 Senast uppdaterad: 2024-07-04Bibliografiskt granskad

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Cortés González, Miguel Ángel

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