RESUMEN
Spirocyclic hypervalent iodine(III) ylides have proven to be synthetically versatile precursors for efficient radiolabelling of a diverse range of non-activated (hetero)arenes, highly functionalised small molecules, building blocks and radiopharmaceuticals from [18F]fluoride ion. Herein, we report the implementation of these reactions onto a continuous-flow microfluidic platform, thereby offering an alterative and automated synthetic procedure of a radiopharmaceutical, 3-[18F]fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18F]FPEB) and a routinely used building block for click-radiochemistry, 4-[18F]fluorobenzyl azide. This new protocol was applied to the synthesis of [18F]FPEB (radiochemical conversion (RCC) = 68 ± 5%) and 4-[18F]fluorobenzyl azide (RCC=68 ± 5%; isolated radiochemical yield = 24±0%). We anticipate that the high throughput microfluidic platform will accelerate the discovery and applications of 18F-labelled building blocks and labelled compounds prepared by iodonium ylide precursors as well as the production of radiotracers for preclinical imaging studies.
RESUMEN
We report that halogenophilic silver(I) triflate permits halogen exchange (halex) nucleophilic (18)F-fluorination of aryl-OCHFCl, -OCF2Br and -SCF2Br precursors under mild conditions. This Ag(I)-mediated process allows for the first time access to a range of (18)F-labeled aryl-OCHF2, -OCF3 and -SCF3 derivatives, inclusive of [(18)F]riluzole. The (18)F-labeling of these medicinally important motifs expands the radiochemical space available for PET applications.
Asunto(s)
Hidrocarburos Fluorados/química , Radioisótopos de Flúor , Estructura Molecular , Compuestos Organometálicos/química , Plata/químicaRESUMEN
In this work, we describe the 18F-labeling of α,α-difluoro-α-(aryloxy)acetic acid derivatives and demonstrate that these building blocks are amenable to post-18F-fluorination functionalization. Protodecarboxylation offers a new entry to 18F-difluoromethoxyarene, and the value of this approach is further demonstrated with coupling processes leading to representative 18F-labeled TRPV1 inhibitors and TRPV1 antagonists.
RESUMEN
[(18)F]FMTEB, [(18)F]FPEB, [(18)F]flumazenil, [(18)F]DAA1106, [(18)F]MFBG, [(18)F]FDOPA, [(18)F]FMT and [(18)F]FDA are prepared from the corresponding arylboronic esters and [(18)F]KF/K222 in the presence of Cu(OTf)2py4. The method was successfully applied using three radiosynthetic platforms, and up to 26 GBq of non-carrier added starting activity of (18)F-fluoride.
Asunto(s)
Ácidos Borónicos/química , Cobre/química , Ésteres/química , Radioisótopos de Flúor , Halogenación , Tomografía de Emisión de Positrones , Catálisis , Trazadores RadiactivosRESUMEN
Arenes substituted with perfluoroalkyl groups are attractive targets for drug and agrochemical development. Exploiting the carbenic character of donor/acceptor diazo compounds, a diversity-oriented synthesis of perfluoroalkylated arenes, for late stage fluorofunctionalization, is described. The reaction of 1-(diazo-2,2,2-trifluoroethyl)arenes with HF, F/Br, F2, CF3H, and CF3SH sources give direct access to a variety of perfluoroalkyl-substituted arenes presenting with incremental fluorine content. The value of this approach is also demonstrated for radiochemistry and positron emission tomography with the [(18)F]-labeling of CF3CHF-, CF3CBrF-, and CF3CF2-arenes from [(18)F]fluoride.