Synthesis of Sulfoxides by Palladium-Catalyzed Arylation of Sulfenate Anions with Aryl Thianthrenium Salts.

A novel and highly efficient Pd-catalyzed arylation of sulfenate anions with aryl thianthrenium salts is demonstrated. This procedure provides a practical protocol to synthesize various diaryl and alkyl aryl sulfoxides in moderate-to-good yields. The new approach shows mild reaction conditions, broad substrate scope, and good functional group tolerance.

A nitroreductase-responsive fluorescence turn-on photosensitizer for lysosomes imaging and photodynamic therapy.

Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet-triplet energy gap (ΔEST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR with kcat/Km as 2.18 × 104 M-1 s-1. The detection limit was determined to be 53.6 ng/mL in 80 % PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity. In addition, the probe exhibited effective ROS generation ability and significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.

The ammonium-promoted formylation of indoles by DMSO and H2O.

DMSO and H2O is an efficient combination in the NH4OAc-promoted formylation of indole, where DMSO serves as a C1 carbon source. The mechanism study reveals that the procedure involves a usual and unusual Pummerer reaction.

Stereospecific Electrophilic Fluorocyclization of α,ß-Unsaturated Amides with Selectfluor.

An efficient fluorocyclization of α,ß-unsaturated amides through a formal halocyclization process is developed. The reaction proceeds under transition-metal-free conditions and leads to the formation of fluorinated oxazolidine-2,4-diones with excellent regio- and diastereoselectivity. The evaluation of the reaction mechanism based on preliminary experiments and density functional theory calculations suggests that a synergetic syn-oxo-fluorination occurs and is followed by an anti-oxo substitution reaction. The reaction opens a new window in the field of stereospecific fluorofunctionalization.

Synthesis of 5-[18F]Fluoro-α-methyl Tryptophan: New Trp Based PET Agents.

Indoleamine 2,3-dioxygenase (IDO1) plays a special role in the biology of various cancer types, because it breaks down the essential amino acid tryptophan for immune cell activation. Upregulation of IDO1 significantly correlates with the number of various T cell types in tumor tissues in melanoma and other cancers, suggesting that IDO expression is linked with effective and ineffective ('exhausted') immune response in cancer. Based on the reported IDO inhibitors (α-Methylated and indole-N-methylated tryptophan (Trp)), here we report the synthesis of potential IDO1 imaging agents through direct introduction of 18F into the tryptophan aromatic ring. Overall, the resulting PET agents could be obtained in high radiochemical purity (>97%) with labeling yield ranges from 4.2-14.9% decay corrected yield. Using Trp as the model compound, our results also demonstrate that 18F could be directly introduced to the Trp backbone at the 4, 5, 6, and 7 position. Moreover, our initial imaging study suggests that 5-[18F]F-L-α-methyl tryptophan (5-[18F]F-AMT) holds great potential for cancer imaging. The success of this approach will provide researchers easy access to a library of Trp/Trp-derivative based PET agents for biomedical research, including potential IDO1 targeted imaging.