[18F]Ethenesulfonyl Fluoride as a Practical Radiofluoride Relay Reagent

Fluorine-18 is the most utilized radioisotope in positron emission tomography (PET), but the wide application of fluorine-18 radiopharmaceuticals is hindered by its challenging labelling conditions. As such, many potentially important radiotracers remain underutilized. Herein, we describe the use of [¹⁸F]ethenesulfonyl fluoride (ESF) as a novel radiofluoride relay reagent that allows radiofluorination reactions to be performed in minimally equipped satellite nuclear medicine centres. [¹⁸F]ESF has a simple and reliable production route and can be stored on inert cartridges. The cartridges can then be shipped remotely and the trapped [¹⁸F]ESF can be liberated by simple solvent elution. We have tested 18 radiolabelling precursors, inclusive of model and clinically used structures, and most precursors have demonstrated comparable radiofluorination efficiencies to those obtained using a conventionally dried [¹⁸F]fluoride source.     

A General Copper‐Mediated Nucleophilic 18F Fluorination of Arenes

Molecules labeled with fluorine‐18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (S_NAr) with [¹⁸F]F^?. In the ideal case, the ¹⁸F fluorination of these substrates would be performed through reaction of [¹⁸F]KF with shelf‐stable readily available precursors using a broadly applicable method suitable for automation. Herein, we describe the realization of these requirements with the production of ¹⁸F arenes from pinacol‐derived aryl boronic esters (arylBPin) upon treatment with [¹⁸F]KF/K₂₂₂ and [Cu(OTf)₂(py)₄] (OTf=trifluoromethanesulfonate, py=pyridine). This method tolerates electron‐poor and electron‐rich arenes and various functional groups, and allows access to 6‐[¹⁸F]fluoro‐L ‐DOPA, 6‐[¹⁸F]fluoro‐m‐tyrosine, and the translocator protein (TSPO) PET ligand [¹⁸F]DAA1106.     

Organomediated Enantioselective 18F Fluorination for PET Applications

The first organomediated asymmetric ¹⁸F fluorination has been accomplished using a chiral imidazolidinone and [¹⁸F]N‐fluorobenzenesulfonimide. The method provides access to enantioenriched ¹⁸F‐labeled α‐fluoroaldehydes (>90 % ee), which are versatile chiral ¹⁸F synthons for the synthesis of radiotracers. The utility of this process is demonstrated with the synthesis of the PET (positron emission tomography) tracer (2S,4S)‐4‐[¹⁸F]fluoroglutamic acid.     

Fast and Efficient 18F‐Labeling by [18F]Fluorophenylazocarboxylic Esters

Introduction of [¹⁸F]fluoride ion into the aromatic core of phenylazocarboxylic esters was achieved in only 30 seconds, with radiochemical yields of up to 95 % (85(±10) %). For labeling purposes, the resulting ¹⁸F‐substituted azoester can be further converted in radical‐arylation reactions to give biaryls, or in substitutions at its carbonyl unit to produce azocarboxamides.     

Cover Picture: Compartmentalization of Chemically Separated Components into Droplets (Angew. Chem. Int. Ed. 15/2009)

Electroosmotic‐flow‐driven droplet generation integrated with capillary electrophoresis (CE) allows the molecular components separated by CE to be compartmentalized into a stream of droplets, as reported by D. T. Chiu and co‐workers in their Communication on page 2719 ff. and illustrated on the cover picture. After separation and droplet compartmentalization, the droplet‐confined bands either can be docked and studied on‐chip or removed off‐chip for a second‐dimension separation and further analysis.