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Aldolases are powerful C−C bond‐forming enzymes with high stereoselectivity and broad substrate scope in biocatalysis, but their ability to stereoselectively construct tertiary alcohols has not been fully explored. Herein, we demonstrate that vicinal diones and α‐keto esters are electrophiles that can be accepted by both natural and computationally designed aldolases via various catalytic mechanisms. This method allows for the efficient asymmetric synthesis of small molecules with tertiary alcohols, including noncanonical amino acids. This study presents the first types of generic nonnatural substrates of aldolases and reveals new opportunities for the use of aldolases in the synthesis of versatile chiral synthons. [ABSTRACT FROM AUTHOR]

Nine new germacranolides, sylvaticalides A−H (1 – 9), and three known analogues (10–12) were isolated from the aerial part of Vernonia sylvatica. Their structures were established using comprehensive spectroscopic analysis, including high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. Their absolute configurations were determined by X-ray diffraction experiments. The anti-inflammatory activities of all isolated compounds were assessed by evaluating their inhibitory effects on the nuclear factor kappa B (NF-κB) pathway, which was activated by lipopolysaccharide (LPS)-stimulated human THP1-Dual cells, and the interferon-stimulated gene (ISG) pathway, activated by STING agonist MSA-2 in the same cell model. Compounds 1 , 2 and 6 showed inhibitory effects on the NF-κB and ISG signaling pathways, with IC 50 values ranging from 4.12 to 10.57 μmol·L−1. [ABSTRACT FROM AUTHOR]

Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy- N -demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N -oxide (5), were isolated from the aerial parts and roots of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC 50 value of 0.525 ± 0.140 μM, which was comparable with the positive control, huperzine A (IC 50 = 0.143 ± 0.029 μM). Unlabelled Image [ABSTRACT FROM AUTHOR]

Background: The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs) as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS., Methods: Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients' age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis., Results: Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23 patients with pyrrolizidine alkaloid-associated HSOS, ten recovered, four developed chronic disease, eight died, and one underwent liver transplantation within 6 months after onset. Blood PPAs were detectable in 24 of 40 patients with concentrations from 0.05 to 74.4 nM. Sensitivity and specificity of the test for diagnosis of pyrrolizidine alkaloid-associated HSOS were 100% (23/23) and 94.1% (23/24), respectively. The positive predictive value was 95.8% and the negative predictive value was 100%, whereas the positive likelihood ratio was 23.81. The level of blood PPAs in the severe group (died or received liver transplantation) was significantly higher than that in the recovery/chronicity group (P=0.004)., Conclusion: Blood PPAs measured by ultra-performance liquid chromatography-tandem mass spectrometry are highly sensitive and specific for pyrrolizidine alkaloid-associated HSOS. The blood PPA concentration is related to the severity and clinical outcome of pyrrolizidine alkaloid-associated HSOS.

A new carbazole alkaloid, named clausine Z, has been isolated from the stems and leaves of Clausena excavata Burm. (Rutaceae). Its structure was established by spectroscopic methods. The compound exhibits inhibitory activity against cyclin-dependent kinase 5 (CDK5) and shows protective effects on cerebellar granule neurons in vitro.