F-18-Trifluoromethanesulfinate Enables Direct C-H F-18-Trifluoromethylation of Native Aromatic Residues in Peptides

Kee CW; Tack O; Guibbal F; Wilson TC; Isenegger PG; Imiolek M; Verhoog S; Tilby M; Boscutti G; Ashworth S; Chupin J; Kashani R; Poh AWJ; Sosabowski JK; Macholl S; Plisson C; Cornelissen B; Willis MC; Passchier J; Davis BG; Gouverneur V

Journal of the American Chemical Society, Vol.142, No.3, 1180-1185, 2020

Kee CW, Tack O, Guibbal F, Wilson TC, Isenegger PG, Imiolek M, Verhoog S, Tilby M, Boscutti G, Ashworth S, Chupin J, Kashani R, Poh AWJ, Sosabowski JK, Macholl S, Plisson C, Cornelissen B, Willis MC, Passchier J, Davis BG, Gouverneur V

F-18 labeling strategies for unmodified peptides with [F-18]fluoride require F-18-labeled prosthetics for bioconjugation more often with cysteine thiols or lysine amines. Here we explore selective radical chemistry to target aromatic residues applying C-H F-18-trifluoromethylation. We report a one-step route to [F-18]CF3SO2NE4 from [F-18]fluoride and its application to direct [F-18]CF3 incorporation at tryptophan or tyrosine residues using unmodified peptides as complex as recombinant human insulin. The fully automated radiosynthesis of octreotide[Trp(2-(CF2F)-F-18)] enables in vivo positron emission tomography imaging.