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A robust Pd(0)-catalyzed decarboxylation alkylation has been developed to construct quaternary stereocenters through the use of chiral tert -butanesulfinamide as the directing group. This strategy provides a simple and efficient route to the construction of quaternary chiral centers at the α-position of chiral sulfinamides, with high diastereoselectivities and high yields. [ABSTRACT FROM AUTHOR]

This paper describes an efficient method for constructing cyclic β-amino acids bearing quaternary stereocenters. NaHMDS-promoted asymmetric α-alkylation was employed to obtain the key intermediates with quaternary stereogenic centers, which were subsequently reduced by NaBH4 in 10% methanol in THF, with high yields and high diastereoselectivities. By removing the allyl ester group and the chiral auxiliary, the corresponding cyclic β-amino acid hydrochlorides were finally obtained. [ABSTRACT FROM AUTHOR]

Celastrol (Cel), derived from the traditional herb Tripterygium wil fordii Hook. f., has anti-inflammatory, anti-tumor, and immunoregulatory activities. Renal dysfunction, including acute renal failure, has been reported in patients following the administration of Cel-relative medications. However, the functional mechanism of nephrotoxicity caused by Cel is unknown. This study featured combined use of activity-based protein profiling and metabolomics analysis to distinguish the targets of the nephrotoxic effects of Cel. Results suggest that Cel may bind directly to several critical enzymes participating in metabolism and mitochondrial functions. These enzymes include voltage-dependent anion-selective channel protein 1 (essential for maintaining mitochondrial configurational and functional stability), pyruvate carboxylase (involved in sugar isomerization and the tricarboxylic acid cycle), fatty acid synthase (related to β-oxidation of fatty acids), and pyruvate kinase M2 (associated with aerobic respiration). Proteomics and metabolomics analysis confirmed that Cel-targeted proteins disrupt some metabolic biosynthetic processes and promote mitochondrial dysfunction. Ultimately, Cel aggravated kidney cell apoptosis. These cumulative results deliver an insight into the potential mechanisms of Cel-caused nephrotoxicity. They may also facilitate development of antagonistic drugs to mitigate the harmful effects of Cel on the kidneys and improve its clinical applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ethnopharmacological relevance: G. uralensis Fisch. ( Glycyrrhiza uralensis ) is an ancient and widely used traditional Chinese medicine with good efficacy in clearing heat and detoxifying action. Studies suggest that Glycyrrhiza Uralensis Polysaccharides (GUP), one of the major components of G. uralensis, has anti-inflammatory, anti-cancer and hepatoprotective effects., but its exact molecular mechanism has not been explored in depth. Aim of the study: Objectives of our research are about exploring the anti-inflammatory role of GUP and the mechanisms of its action. Materials and methods: ELISA kits, Western blotting, immunofluorescence, quantitative real-time PCR, immunoprecipitation and DMXAA-mediated STING activation mice models were performed to investigate the role of GUP on the cGAS-STING pathway. To determine the anti-inflammatory effects of GUP, cecal ligation and puncture (CLP) sepsis models were employed. Results: GUP could effectively inhibit the activation of the cGAS-STING signaling pathway accompany by a decrease the expression of type I interferon-related genes and inflammatory factors in BMDMs, THP-1, and human PBMCs. Mechanistically, GUP does not affect the oligomerization of STING, but affects the interaction of STING with TBK1 and TBK1 with IRF3. Significantly, GUP had great therapeutic effects on DMXAA-induced agonist experiments in vivo as well as CLP sepsis in mice. Conclusion: Our studies suggest that GUP is an effective inhibitor of the cGAS-STING pathway, which may be a potential medicine for the treatment of inflammatory diseases mediated by the cGAS-STING pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hui, Kan, Qin, He, Zhao, Li, Bai, Wen, Mou, Hou, Wei, Lin, Xiao, Xu and Bai.)