RESUMO
We report a method for labeling arylvinyltrifluoromethanes with carbon-11 (t1/2 = 20.4 min) as representatives of a new radiolabeled chemotype that has potential for developing radiotracers for biomedical imaging with positron emission tomography. Treatment of (E)-arylvinyl(phenyl)iodonium tosylates (1a-1k) with [11C[CuCF3 gave the corresponding [11C]arylvinyltrifluoromethanes ([11C]2a-[11C]2k) in high radiochemical yields (90-97%) under rapid (2 min) and mild (60 °C) conditions.
Assuntos
Clorofluorcarbonetos de Metano/síntese química , Hidrocarbonetos Iodados/química , Compostos Organometálicos/química , Compostos de Tosil/química , Radioisótopos de Carbono , Clorofluorcarbonetos de Metano/química , Estrutura MolecularRESUMO
Positron emission tomography (PET) is an important imaging modality for biomedical research and drug development. PET requires biochemically selective radiotracers to realize full potential. Fluorine-18 (t1/2 = 109.8 min) is a major radionuclide for labeling such radiotracers but is only readily available in high activities from cyclotrons as [18F]fluoride ion. [18F]fluoroform has emerged for labeling tracers in trifluoromethyl groups. Prior methods of [18F]fluoroform synthesis used difluoro precursors in solution and led to high dilution with carrier and low molar activity (Am). We explored a new approach for the synthesis of [18F]fluoroform based on the radiosynthesis of [18F]fluoromethane from [18F]fluoride ion and then cobaltIII fluoride mediated gas phase fluorination. We estimate that carrier dilution in this process is limited to about 3-fold and find that moderate to high Am values can be achieved. We show that [18F]fluoroform so produced is highly versatile for rapidly and efficiently labeling various chemotypes that carry trifluoromethyl groups, thereby expanding prospects for developing new PET radiotracers.
Assuntos
Clorofluorcarbonetos de Metano , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Clorofluorcarbonetos de Metano/síntese química , Clorofluorcarbonetos de Metano/química , Radioisótopos de Flúor/química , Marcação por Isótopo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/químicaRESUMO
We describe a simple, metal- and oxidant-free photochemical strategy for the direct trifluoromethylation of unactivated arenes and heteroarenes under either ultraviolet or visible light irradiation. We demonstrated that photoexcited aliphatic ketones, such as acetone and diacetyl, can be used as promising low-cost radical initiators to generate CF3 radicals from sodium triflinate efficiently. The broad utility of this strategy and its benefit to medicinal chemistry are demonstrated by the direct trifluoromethylation of unprotected bidentate chelating ligand, xanthine alkaloids, nucleosides, and related antiviral drug molecules.
Assuntos
Clorofluorcarbonetos de Metano/síntese química , Hidrocarbonetos Aromáticos/química , Hidrocarbonetos Aromáticos/efeitos da radiação , Acetona/química , Alcaloides/química , Antivirais/síntese química , Antivirais/química , Quelantes/química , Clorofluorcarbonetos de Metano/química , Diacetil/química , Química Verde/métodos , Indicadores e Reagentes , Cetonas/química , Ligantes , Luz , Processos Fotoquímicos , Raios UltravioletaRESUMO
Gem-difluoromethylated and trifluoromethylated derivatives of DMDP-related iminosugars have been synthesized from cyclic nitrones 12, 13, 18, ent-18 or 23 and nitrone-derived aldehydes 20 or ent-20. The fluorinated iminosugars were assayed against various glycosidases, and ent-8 showed moderate but selective α-l-rhamnosidase inhibition. Difluoro or trifluoro units influenced the inhibitory activities of iminosugars in a more complex manner than single fluoro substitution. This may be correlated with their highly hydrophobic character and strong electron-withdrawing effect.
Assuntos
Clorofluorcarbonetos de Metano/química , Glicosídeo Hidrolases/antagonistas & inibidores , Hidrocarbonetos Fluorados/química , Imino Furanoses/química , Óxidos de Nitrogênio/química , Clorofluorcarbonetos de Metano/síntese química , Ciclização , Hidrocarbonetos Fluorados/síntese química , Imino Furanoses/síntese química , Estrutura MolecularRESUMO
Trifluoromethylative lactonization of both terminal and internal alkenoic acids by photoredox catalysis has been developed. The use of a Ru photocatalyst and Umemoto's reagent as a CF3 source is key in the present carbolactonization. This is the first example of a highly endo- and diastereoselective synthesis of CF3-substituted five-, six-, and seven-membered ring lactones from internal alkenoic acids.
Assuntos
Alcenos/química , Clorofluorcarbonetos de Metano/síntese química , Lactonas/síntese química , Catálise , Clorofluorcarbonetos de Metano/química , Ciclização , Lactonas/química , Estrutura Molecular , EstereoisomerismoRESUMO
A new strategy towards [(18)F]trifluoromethyl-containing compounds is developed. [(18)F]trifluoromethane is synthesised in a fast and efficient manner and subsequently used in the reaction with aldehydes and ketones forming [(18)F]trifluoromethyl carbinols in good yields.
Assuntos
Clorofluorcarbonetos de Metano/síntese química , Radioisótopos de Flúor/química , Aldeídos/química , Clorofluorcarbonetos de Metano/química , Cetonas/química , Tomografia por Emissão de PósitronsRESUMO
A practical and efficient synthesis of C(3)-trifluoromethanesulfanylated hexahydropyrrolo[2,3-b]indoles 5 from tryptamine derivatives was described. The features of this synthesis included electrophilic activation of C(3) of tryptamine derivatives with "CF(3)S(+)" and cascade ring cyclization by carbamate nucleophile attacking at C(2). Surprisingly, when Lewis acid (BF(3)·OEt(2)) was used as activator instead of proton acid (TsOH·H(2)O) for the electrophilic trifluoromethanesulfanylation of tryptamine derivatives, the uncyclized product 6 was formed preferentially. This sequential trifluoromethanesulfanylation-cyclization protocol was used to synthesize several pyrrolidinoindolinic alkaloid analogues. The cytotoxicity activities of these trifluoromethanesulfanylated alkaloid analogues were evaluated against three cancer cell lines (K562, HeLa, L929).