Asymmetric Synthesis of Axially Chiral Naphthyl-C3-indoles via a Palladium-Catalyzed Cacchi Reaction.

Atropoisomeric biaryl motifs are widely found in natural products and bioactive compounds as well as chiral catalysts and ligands. Various efficient approaches have been disclosed for the construction of chiral six-six biaryl skeletons. In contrast, the enantioselective synthesis of axially chiral arylindoles through the strategy of de novo construction, other than the asymmetric functionalization of indoles, remain a challenging task. Herein we report an efficient Pd(0)/(S)-Segphos-catalyzed atroposelective Cacchi reaction of 2-alkynylanilines with sterically congested naphthyl halides, which afforded an array of naphthyl-C3-indoles in high yields with good to excellent atroposelectivities. The addition of water and the modulation of the manipulation procedure by premixing the palladium complex and the naphthyl halide were the keys to success. The conformational stability of the obtained axially chiral naphthyl-C3-indole containing a synthetically more-valuable free NH moiety is revealed through kinetic experiments.

Qiyusanlong decoction suppresses lung cancer in mice via Wnt/ß-catenin pathway.

Lung cancer is one of the most fatal cancers due to its high metastatic rate. Traditional Chinese medicine has been used in cancer patients for decades to improve quality of life and prolong survival time. The present study used a novel Qiyusanlong (QYSL) decoction composed of 10 kinds of Chinese medicine including astragalus membranaceus (Huangqi), polygonatumod oratum (yuzu), scolopendra (tianlong), pberetima (dilong), solanum nigrum (longkui), herbahedyotis (baihushecao), semen coicis (yiyiren), euphorbia helioscopia (zeqi), curcuma longa (eshu) and tendril-leaved fritillary bulb (chuanbei). The effects and function of the QYSL decoction remain to be elucidated. The present study established a mouse xenograft model using Lewis lung carcinoma cell injection and administered different doses of QYSL decoction to the mice. It was demonstrated that the chemotherapy drug Cisplatin (DDP) and QYSL decoction repressed lung tumor growth, and the inhibitory effect of DDP was more significant. Furthermore, QYSL decoction and DDP modulated the expression of regulatory proteins in the Wnt/ß­catenin pathway, including Wnt1, Wnt2, Wnt5a and glycogen synthase kinase 3ß, detected by western blotting, and affected the signals of cluster of differentiation 44 variation 6 and Survivin in tumor tissues, examined via immunohistochemistry. The combination of QYSL decoction and DDP enhanced the inhibitory effect. These data demonstrated that the QYSL decoction repressed lung tumor development via the Wnt/ß­catenin pathway. The therapeutic effect of QYSL decoction alone was milder compared with DDP, however the combination of QYSL decoction and chemotherapy exhibited an increased the rapeutic effect compared with the treatments administered alone. These findings revealed the function of QYSL decoction as a lung cancer treatment and provided insight for a novel lung cancer therapy.