Biphasic effects of ethanol consumption on N,N-dimethylformamide-induced liver injury in mice.

N,N-Dimethylformamide (DMF) is a well-documented occupational hazardous material, which can induce occupational liver injury. The current study was designed to investigate whether ethanol consumption can affect DMF-induced hepatotoxicity and the potential underlying mechanisms involved. We found that a single dose of ethanol (1.25, 2.5, or 5 g/kg bw by gavage) significantly repressed the increase in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and alleviated the liver histopathological changes in mice challenged with 3 g/kg DMF. In contrast, long-term moderate drinking (2.5 g/kg bw) significantly aggravated the repeated DMF (0.7 g/kg bw) exposure-induced increase in the serum ALT and AST activities. Mechanistically, acute ethanol consumption suppressed DMF-induced activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome, while long-term moderate ethanol consumption promoted hepatocyte apoptosis in the mouse liver. Notably, cytochrome P4502E1 (CYP2E1) protein level and activity in mouse livers were not significantly affected by ethanol per se in the two models. These results confirm that regular drinking can increase the risk of DMF-induced hepatotoxicity, and suggest that DMF-handling workers should avoid consuming ethanol to reduce the risk of DMF-indued liver injury.

Diastereodivergent and Regioselective Synthesis of Tetrahydrofuro[2,3-b]furans with Four Consecutive Stereocenters.

Base-catalyzed diastereodivergent and regioselective domino processes of triketone enones with arylacetaldehydes for the synthesis of tetrahydrofuro[2,3-b]furans with four consecutive stereocenters are reported. Good yields and diastereoselectivities are obtained when DBU is employed as a catalyst; in contrast, Et3N delivers a different diastereomer in excellent diastereoselectivity. This work offers many advantages, including switchable diastereoselectivity, cheap base catalysts, and a simple operation.

Diversity-Oriented Catalytic Asymmetric Dearomatization of Indoles with o-Quinone Diimides.

Herein, the first diversity-oriented catalytic asymmetric dearomatization of indoles with o-quinone diimides (o-QDIs) is reported. The catalytic asymmetric dearomatization (CADA) of indoles is one of the research focuses in terms of the structural and biological importance of dearomatized indole derivatives. Although great achievements have been made in target-oriented CADA reactions, diversity-oriented CADA reactions are regarded as more challenging and remain elusive due to the lack of synthons featuring multiple reaction sites and the difficulty in precise control of chemo-, regio-, and enantio-selectivity. In this work, o-QDIs are employed as a versatile building block, enabling the chemo-divergent dearomative arylation and [4 + 2] cycloaddition reactions of indoles. Under the catalysis of chiral phosphoric acid and mild conditions, various indolenines, furoindolines/pyrroloindolines, and six-membered-ring fused indolines are collectively prepared in good yields with excellent enantioselectivities. This diversity-oriented synthesis protocol enriches the o-quinone chemistry and offers new opportunities for CADA reactions.