Protective effects of a novel water-soluble biphenyl compound WLP-S-14 against acute-on-chronic liver failure in rats.

This study investigated the therapeutic effects of a water-soluble biphenyl compound, WLP-S-14, in acute-on-chronic liver failure (ACLF). Wistar rats were injected intraperitoneally with porcine serum twice a week for 8 weeks prior to administration of 600 mg/kg D-galactosamine and 50 µg/kg lipopolysaccharide to induce ACLF. Study groups were treated intravenously with saline or with 100 or 200 mg/kg WLP-S-14. WLP-S-14 ameliorated ACLF with significant reductions in the mortality rate and transaminase levels, indicating improved liver function. The mechanism underlying these effects may involve decreased levels of tumor necrosis factor-α and interleukin-6, with associated inhibition of apoptotic pathways.

Changing the reaction pathway by NHC/Brønsted base cooperative catalysis: highly stereoselective synthesis of multifunctional benzo[a]fluoren-11-ones from the dimerization of 2-(aroylvinyl)arylaldehydes.

The unprecedented NHC/Brønsted base-cocatalyzed dimerization reaction of 2-(aroylvinyl)arylaldehydes was reported. In the presence of a triazole carbene catalyst alone, no reaction of 2-(aroylvinyl)arylaldehydes was observed. However, the combination of triazole carbene and 4-methoxyphenolate efficiently catalyzed the dimerization of 2-(aroylvinyl)arylaldehydes to proceed through a benzoin-Michael-Michael reaction cascade, producing 6-aroyl-5-(aroylmethyl)-11a-hydroxybenzo[a]fluoren-11-ones as the sole diastereomers in good yields.

A convenient semisynthesis of myricetin-3-O-ß-d-glucuronide.

Myricetin-3-O-ß-d-glucuronide, a bioactive flavonol glycoside, was synthesized effectively starting from myricetrin in a total yield of 49.2%. The structures of all synthetic compounds were confirmed by (1)H, (13)C NMR, and HR-MS techniques.

Identification of impurities in methotrexate drug substances using high-performance liquid chromatography coupled with a photodiode array detector and Fourier transform ion cyclotron resonance mass spectrometry.

RATIONALE: Methotrexate (MTX) is an antineoplastic therapeutic medicine that acts as an antimetabolite of folic acid. In this study we identified the impurities in MTX drug substances produced by different manufacturers and in different batches using high-performance liquid chromatography coupled with a photodiode array detector and Fourier transform ion cyclotron resonance mass spectrometry (HPLC-PDA/FTICR-MS). METHODS: MTX and its impurities were separated on a Restek Pinnacle II C18 column (250 × 4.6 mm, 5 µm) with a gradient elution system composed of 0.2% formic acid and acetonitrile at a flow rate of 1.0 mL/min. Ultraviolet (UV) detection was set at 305 nm. Mass detection was carried out using FTICR-MS with full-scan mass analysis at a resolving power of 100 000 coupled with multiple-stage mass analysis using a parent list of compounds. RESULTS: Fifteen impurities were detected in MTX drug substances, and their structures were predicted from using HPLC-PDA/FTICR-MS data, including their UV spectra, high-resolution mass spectrometry (HRMS), fragmentation patterns, and MS(n) spectra. Ten of the impurities detected in the MTX drug substances are reported for the first time. There was a high abundance of esterified impurities in some batches of MTX drug substances, over the identification threshold of International Conference on Harmonization (ICH) guidelines, which requires particular attention. CONCLUSIONS: This paper describes a HPLC-PDA/FTICR-MS method to profile and identify impurities in MTX drug substances. The results suggest that HPLC-PDA/FTICR-MS is a valuable analytical technique for the rapid identification of impurities.

The synthesis of justicidinoside B and its atropisomer.

The first synthesis of justicidinoside B and its atropisomer was reported and their absolute configurations were determined by the CD exciton chirality method. The structures were confirmed by (1)H NMR, (13)C NMR, and HRMS.

Total synthesis of 6'-hydroxyjusticidin A.

The first total synthesis of 6'-hydroxyjusticidin A, isolated from Justicia procumbens L. with good inhibitory activity against cancer cells, has been accomplished. The structure was confirmed by ¹H NMR, ¹³C NMR, and HR-ESI-MS. The key steps involved a Diels-Alder cycloaddition reaction and a reduction in NaBH4.

Total synthesis of adicardin.

The first synthesis of adicardin, a compound with anti-chronic renal failure activity isolated from Hydrangea macrophylla, has been described. The structures of the target compound and intermediates have been validated by MS, NMR, and identical with the natural product.

Synthesis and enantiomeric resolution of (+/-)-pinocembrin.

A convenient method for the synthesis and enantiomeric resolution of ( +/- )-pinocembrin has been developed. This route involves the hydrogenation of 5,7-dihydroxyflavone, the derivatization of racemic pinocembrin with chiral amine, and the separation of the diastereoisomers due to their different physical properties.