Site‐Specific Deoxyfluorination of Small Peptides with [¹⁸F]Fluoride

Abstract

Radiolabeled receptor-binding peptides are an important class of positron emission tomography tracers owing to achievable high binding affinities and their rapid blood clearance. Herein, a method to introduce a 4-[ F]fluoro-phenylalanine residue into peptide sequences is reported, by chemoselective radio-deoxyfluorination of a tyrosine residue using a traceless activating group. The replacement of only one hydrogen atom with [ F]fluoride results in minimal structural perturbation of the peptide, which is desirable in the labeling of tracer candidates.

Closing the gap between 19F and 18F chemistry

“…The use of prosthetic groups for the direct 18 F-labelling of peptides was firstly reported by Becaud in 2009 (Fig. 10B) (Rickmeier and Ritter 2018). Direct 18 F-fluorination of model trimethylammonium-substituted modified peptides with [ 18 F]KF-Kryptofix enabled the synthesis of 18 F-labelled tetrapeptides and analogues of bombesin peptides under relatively mild conditions.…”

Site‐Selective Late‐Stage Aromatic [18F]Fluorination via Aryl Sulfonium Salts

“…Most notably, practical [ 18 F]fluorodemetallation reactions mediated by copper that proceed on a large variety of small molecules have been developed by the groups of Gouverneur, Sanford and Scott, and Neumaier . Our group has reported deoxyfluorination reactions that in addition can also functionalize small peptides . Sanford, Scott, and co‐workers have described a Cu‐mediated two‐step [ 18 F]fluorination of electron‐rich arenes using hypervalent iodine compounds .…”

“…Elution of the [ 18 F]fluoride from the anion exchange cartridge is commonly achieved with an aqueous solution of a base . Aryldibenzothiophenium salts can be used directly for elution of [ 18 F]fluoride, which avoids the addition of bases or kryptofix . No special care is required to exclude air or moisture at any stage of the radio‐synthesis, and the radiolabeled product can be readily separated from the starting material due to the pronounced polarity difference owing to the cationic sulfonium salt.…”

Ein Fest der Wissenschaft inmitten der Natur: Die 54. Bürgenstock‐Konferenz

“…Am Mittwochmorgen gab Tobias Ritter (MPI, Mülheim) einen Überblick über seine neuesten Ergebnisse zur späten Funktionalisierung. In seinem Vortrag beschrieb er eine späte Arenhydroxylierung, eine spezifische Desoxyfluorierung von kleinen Peptiden, eine direkte Amination von Arenen und eine selektive aromatische C‐H‐Funktionalisierung durch Thianthrenierung, und er gab eine Zusammenfassung über den Einsatz von PhenoFluor ® (Abbildung ) als praktisches Fluorierungsreagenz . In seinem Ansatz zur konzertierten nucleophilen aromatischen Substitution mit 19 F und 18 F wurde festgestellt, dass das Substratspektrum nicht auf elektronenarme Arene beschränkt ist, da bei der konzertierten nucleophilen aromatischen Substitutionsreaktion (CS N Ar) kein Meisenheimer‐Zwischenprodukt gebildet wird.…”