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An efficient iron-catalyzed C–O bond functionalization of butyrolactam derivatives with various N-/C-nucleophiles to enable the synthesis of pharmaceutically important butyrolactam derivatives has been developed here. The versatility of the present methodology is demonstrated for direct amination and carbonation by using a variety of sulfonamides, amines, amides, indoles, and 1,3-dicarbonyl compounds under mild conditions. The reaction also showed a wide substrate scope and synthetic simplicity. Additionally, only alcohol was produced as the by-product in all cases.

Breast cancer is one of the malignant tumors with the highest morbidity and mortality rate. Numerous efficient anti-breast cancer drugs are being derived from the development of natural products. Voacamine (VOA), a bisindole alkaloid isolated from Voacanga africana Stapf, possesses various pharmacological and biological activities.In this study, we investigated the efficacy of VOA against breast cancer cells and elucidated the underlying mechanisms in vitro and in vivo.Human breast cancer cell line MCF-7 and mouse breast cancer cell line 4T1 were used to study the underlying anti-cancer mechanisms of VOA. The proliferation was detected by MTT, colony formation, cell proliferation and wound-healing migration assays. Flow cytometry was utilized to determine the level of reactive oxygen species (ROS) cell-cycle, apoptosis and mitochondrial membrane potential. The target proteins were analyzed by Western blot. Molecular docking was performed and scored by AutoDock. Subcutaneous cancer models in mice were established to evaluate the anticancer effects in vivo.Our results demonstrated that VOA selectively suppressed breast cancer MCF-7 and 4T1 cells proliferation with ICThese findings revealed the novel properties of VOA in promoting apoptosis of breast cancer cells by activating mitochondrial-associated apoptosis signaling pathway and inhibiting PI3K/Akt/mTOR signaling pathway and significantly decreasing tumor size without detecting appreciable toxicity. In summary, the present results demonstrated VOA could be an encouraging drug candidate to cure breast cancer, exhibiting an effective method to exploit unique drugs from natural components.

Digenetic trematodes of the genus Clinostomum are widely distributed in many species of freshwater fish and are known to cause the zoonotic disease Halzoun. Humans may become accidental hosts if they ingest raw freshwater fish containing metacercaria of Clinostomum complanatum, which causes pharyngitis or laryngitis. The yellow grub parasitizing cultivated ayu (Plecoglossus altivelis) and loach (Misgurnus anguillicaudatus) was one of the most serious problems in fish farms from 1977 to 1979 in Taiwan. The present study revealed, for the first time, frequent occurrence of C. complanatum metacercaria in various fish species in a natural environment, the Dahan River, in Taiwan. We examined 1503 fish specimens belonging to four families and 162 snails representing six species. C. complanatum metacercaria was mainly from the fish family Cyprinidae, and only cercaria from the snail Radix swinhoei was recovered. The prevalence and mean intensity of metacercaria were 9.8% and 9.35 parasites/infected fish, respectively. The prevalence of cercaria was low, 0.62%, in snails. Acrossocheilus paradoxus, Zacco barbata, Zacco pachycephalus, Zacco platypus, Onychostoma barbatula, and Hemibarbus labeo are new host records. Metacercariae were primarily found in the operculum, mandible, muscle, and oral cavity of fish. Morphological description and molecular analysis with 18S rDNA sequencing allowed for rapidly identifying C. complanatum. Encysted and excysted metacercariae cultivated at 22 °C in physiological saline died within 60 h. The mean intensity of infection increased with an increasing length of Z. pachycephalus. We found no association between monthly parasite prevalence and mean intensity at each sampling location. No C. complanatum metacercaria survived after 8 h of salting. The Dahan River has suitable conditions and hosts (snails, fish, and fish-eating birds) for maintaining the life cycle of C. complanatum.

A bifunctional squaramide-catalyzed reaction of azlactones with o-quinone methides in situ generated from 2-(1-tosylalkyl)-phenols has been successfully developed under basic conditions, providing an efficient and mild access to chiral dihydrocoumarins bearing adjacent tertiary and quaternary stereogenic centers in high yields with excellent diastereo- and enantioselectivities.