Development of [18F]F-5-OMe-Tryptophans through Photoredox Radiofluorination: A New Method to Access Tryptophan-Based PET Agents.

Although various radiolabeled tryptophan analogs have been developed to monitor tryptophan metabolism using positron emission tomography (PET) for various human diseases including melanoma and other cancers, their application can be limited due to the complicated synthesis process. In this study, we demonstrated that photoredox radiofluorination represents a simple method to access novel tryptophan-based PET agents. In brief, 4-F-5-OMe-tryptophans (l/d-T13) and 6-F-5-OMe-tryptophans (l/d-T18) were easily synthesized. The 18F-labeled analogs were produced by photoredox radiofluorination with radiochemical yields ranging from 2.6 ± 0.5% to 32.4 ± 4.1% (3 ≤ n ≤ 5, enantiomeric excess ≥ 99.0%) and over 98.0% radiochemical purity. Small animal imaging showed that l-[18F]T13 achieved 9.58 ± 0.26%ID/g tumor uptake and good contrast in B16F10 tumor-bearing mice (n = 3). Clearly, l-[18F]T13 exhibited prominent tumor uptake, warranting future evaluations of its potential usage in precise immunotherapy monitoring.

11C, 12C and 13C-Cyanation of Electron-Rich Arenes via Organic Photoredox Catalysis.

As a non-invasive imaging technology, positron emission tomography (PET) plays a crucial role in personalized medicine, including early diagnosis, patient screening, and treatment monitoring. The advancement of PET research depends on the discovery of new PET agents, which requires the development of simple and efficient radiolabeling methods in many cases. As bioisosteres for halogen and carbonyl moieties, nitriles are important functional groups in pharmaceutical and agrochemical compounds. Here, we disclose a mild organophotoredox-catalyzed method for efficient cyanation of a broad spectrum of electron-rich arenes, including abundant and readily available veratroles and pyrogallol trimethyl ethers. Notably, the transformations not only are compatible with various affordable 12C and 13C-cyanide sources, but also could be applied to carbon-11 synthons to incorporate [11C]nitriles into arenes. The aryl [11C]nitriles can be further derivatized to [11C]carboxylic acids, [11C]amides, and [11C]alkyl amines. The newly developed reaction can serve as a powerful tool for generating new PET agents.

Phototherapy and multimodal imaging of cancers based on perfluorocarbon nanomaterials.

Phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), possesses unique characteristics of non-invasiveness and minimal side effects in cancer treatment, compared with conventional therapies. However, the ubiquitous tumor hypoxia microenvironments could severely reduce the efficacy of oxygen-consuming phototherapies. Perfluorocarbon (PFC) nanomaterials have shown great practical value in carrying and transporting oxygen, which makes them promising agents to overcome tumor hypoxia and extend reactive oxygen species (ROS) lifetime to improve the efficacy of phototherapy. In this review, we summarize the latest advances in PFC-based PDT and PTT, and combined multimodal imaging technologies in various cancer types, aiming to facilitate their application-oriented clinical translation in the future.

Borane-Catalyzed Chemoselective and Enantioselective Reduction of 2-Vinyl-Substituted Pyridines.

Herein, we report that highly chemoselective and enantioselective reduction of 2-vinyl-substituted pyridines has been achieved for the first time. The reaction, which uses chiral spiro-bicyclic bisboranes as catalysts and HBpin and an acidic amide as reducing reagents, proceeds through a cascade process involving 1,4-hydroboration followed by transfer hydrogenation of a dihydropyridine intermediate. The retained double bond in the reduction products permits their conversion to natural products and other useful heterocyclic compounds by simple transformations.

Aluminum-catalyzed tunable halodefluorination of trifluoromethyl- and difluoroalkyl-substituted olefins.

Herein, we report unprecedented aluminum-catalyzed halodefluorination reactions of trifluoromethyl- and difluoroalkyl-substituted olefins with bromo- or chlorotrimethylsilane. The interesting feature of these reactions is that one, two, or three fluorine atoms can be selectively replaced with bromine or chlorine atoms by modification of the reaction conditions. The generated products can undergo a variety of subsequent transformations, thus constituting a valuable stock of building blocks for installing fluorine-containing olefin motifs in other molecules.

Spiro-Bicyclic Bisborane Catalysts for Metal-Free Chemoselective and Enantioselective Hydrogenation of Quinolines.

A new series of spiro-bicyclic bisborane catalysts has been prepared by means of hydroboration reactions of C2 -symmetric spiro-bicyclic dienes with HB(C6 F5 )2 and HB(p-C6 F4 H)2 . When used for hydrogenation of quinolines, these catalysts give excellent yields and enantiomeric excesses, and show turnover numbers of up to 460. The most attractive feature of these metal-free hydrogenation reactions was the broad functional-group tolerance, making this method complementary to existing methods for quinoline hydrogenation.

C2 -Symmetric Bicyclic Bisborane Catalysts: Kinetic or Thermodynamic Products of a Reversible Hydroboration of Dienes.

We prepared a new class of chiral C2 -symmetric bicyclic bisborane catalysts by addition reactions of internal dienes with the Piers borane, HB(C6 F5 )2 , and an analogue, HB(p-C6 F4 H)2 . The dependence of the addition pattern on the reaction temperature allowed us to selectively prepare two diastereomeric catalysts from a single diene precursor. The bisboranes prepared in situ exhibited excellent activity (turnover numbers up to 200 at -40 °C) and enantioselectivity (up to 95 % ee) in imine hydrogenation reactions.