A new one-pot preparation of 4-tetrazolyl-3,4-dihydroquinazolines has been reported. The Ugi-azide reactions of 2-azidobenzaldehydes, amines, trimethylsilyl azide, and isocyanides produced azide intermediates without separation, which were treated with isocyanides to give 4-tetrazolyl-3,4-dihydroquinazoline derivatives through a sequential Palladium-catalyzed azide-isocyanide cross-coupling/cyclization reaction in moderate to good yields. The biological evaluation demonstrated that compound 6c inhibited breast cancer cells well and displayed broad applications for synthesis and medicinal chemistry.

Aim To establish a fast, sensitive and accurate high‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) method for determining the monosaccharide content of Qingzhuan Dark Tea polysaccharides in different years (2 years, 5 years and 11 years). Methods The optimised chromatographic conditions were achieved on a C18 column (5.0 μm, 250 mm × 4.6 mm inner diameter). The mobile phase flow rate was 0.9 mL/min and the column temperature was set to 27°C. The aqueous phase A (5 mM aqueous ammonium acetate) and organic phase B (acetonitrile) were used to elute the target analyses isocratically (0–60 min: 18% B). The mass spectrometer detector was equipped with an electron spray ionisation (ESI)source, and multiple reaction monitoring (MRM) mode was used for the determination of 1‐phenyl‐3‐methyl‐5‐pyrazolone (PMP) derived monosaccharides. Results We carried out a comprehensive methodological validation of PMP derived monosaccharides, including linearity, precision, stability and repeatability. Nine monosaccharides (rhamnose, mannose, ribose, glucose, galacturonic acid, xylose, galactose, fucose and arabinose) of Qingzhuan Dark Tea polysaccharides were identified, in which ribose and fucose were reported for the first time. The results showed the contents of these nine monosaccharides differed significantly among different years. Conclusions The validated method is reliable, accurate, repeatable and can be applied to quality assessment of these monosaccharides.

Background Dihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear. Methods After male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing. Results The results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia). Conclusions The results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level).

Dihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear. Herein, after male C57BL/6 mice were fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum AST, ALT and liver TG, MDA were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by LC-MS, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing. The results showed the significant changes including 28 lipids, 4 BAs (23-norDCA, UCA, 7-KDCA and CA), 2 BAs transporters (Mrp2 and Oatp1b2) and 3 GMs (Actinobacteria, Akkermansiaand Faecalibaculum) between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, Faecalibaculum abundance and the ratio of Firmicutes/Bacteroidota, significantly up-regulated 7 lipids and 2 GM (Actinobacteria andAkkermansia). The results suggested that DMY alleviated NASH by up-regulating intestinal probiotics (Actinobacteria and Akkermansia, etc) and inhibiting intestinal harmful bacteria (Erysipelotrichaceaeand Faecalibaculum), thereby regulating the composition and contents of serum BAs and lipids in MCD mice.