Design and Challenges of Radiopharmaceuticals.

This review describes general concepts with regard to radiopharmaceuticals for diagnostic or therapeutic applications that help to understand the specific challenges encountered during the design, (radio)synthesis, in vitro and in vivo evaluation and clinical translation of novel radiopharmaceuticals. The design of a radiopharmaceutical requires upfront decisions with regard to combining a suitable vector molecule with an appropriate radionuclide, considering the type and location of the molecular target, the desired application, and the time constraints imposed by the relatively short half-life of radionuclides. Well-designed in vitro and in vivo experiments allow nonclinical validation of radiotracers. Ultimately, in combination with a limited toxicology package, the radiotracer becomes a radiopharmaceutical for clinical evaluation, produced in compliance with regulatory requirements for medicines for intravenous (IV) injection.

Highly ( Z)-Diastereoselective Synthesis of Trifluoromethylated exo-Glycals via Photoredox and Copper Catalysis.

Highly ( Z)-diastereoselective approaches for the synthesis of trifluoromethylated exo-glycals by copper and photoredox catalysis are described. These complementary reactions are applicable to a wide range of methylene exo-glycals generated from the corresponding pyranoses and furanoses and give trifluoromethylated compounds under mild conditions in moderate to good yields. DFT calculations have allowed a rationalization of the observed ( Z)-stereoselectivity.

Eliminative Deoxofluorination Using XtalFluor-E: A One-Step Synthesis of Monofluoroalkenes from Cyclohexanone Derivatives.

The eliminative deoxofluorination of cyclohexanone derivatives using XtalFluor-E is described. The corresponding monofluoroalkenes are obtained in up to 79% yield. Notably, this one-step procedure occurs at room temperature using readily accessible and cost-effective reagents.

Direct Esterification of Carboxylic Acids with Perfluorinated Alcohols Mediated by XtalFluor-E.

The direct esterification of carboxylic acids with perfluorinated alcohols mediated by XtalFluor-E is reported. The corresponding polyfluorinated esters are obtained in moderate to excellent yields with a broad range of carboxylic acids, including aromatic, heteroaromatic, aliphatic, and nonracemic chiral substrates, using only a slight excess (2 equiv) of the perfluorinated alcohol. Control experiments indicate that the reaction does not proceed through the formation of an acyl fluoride but most likely through a (diethylamino)difluoro-λ4-sulfanyl carboxylate intermediate.