Search

A mild nitration of pyrrolo[2,1‐a]isoquinolines has been reached using sodium nitrite as nitro source in HFIP at ambient temperature. A variety of nitro‐bearing pyrrolo[2,1‐a]isoquinoline derivatives has been efficiently prepared in poor to quantitative yields (28–98 %). These products can be easily transformed to primary amines and amide by simple chemical reactions. Treatment of other nitrogen‐containing heterocycles such as pyrrolo[1,2‐a]quinoline and substituted indoles under this developed reaction system afforded nitro‐bearing N‐heterocycles in relatively lower yields (15–19 %). [ABSTRACT FROM AUTHOR]

We have developed an iron-catalyzed synthesis of pyrrolo[2,1- a ]isoquinoline derivatives with tetrahydroisoquinolines, arylacyl bromides, and nitroolefins. Highly functionalized pyrrolo[2,1- a ]isoquinolines can be obtained in moderate to good yields through a three-component N-alkylation/oxidative 1,3-dipolar cycloaddition/elimination/aromatization cascade. The obtained products in this study can be easily modified by easy chemical transformations to structurally complex molecules bearing privileged framework. [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPS) have been rapidly emerged as legal alternatives to controlled drugs, which raised severe public health issue. The detection and monitoring of its intake by complete metabolic profiling is an urgent and vital task. Untargeted metabolomics approach has been applied for several NPS metabolites studies. Although the number of such works is relatively limited but with a rapidly growing need. The present study aimed to propose a procedure that includes liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis and a signal selection software, MetaboFinder, programed as a web tool. The comprehensive metabolites profile of one kind of NPS, 4-methoxy-α-pyrrolidinovalerophenone (4-MeO-α-PVP), was studied by using this workflow. In this study, two different concentrations of 4-MeO-α-PVP along with as blank sample were incubated with human liver S9 fraction for the conversion to their metabolites and followed by LC-MS analysis. After retention time alignment and feature identification, 4640 features were obtained and submitted to statistical analysis for signal selection by using MetaboFinder. A total of 50 features were considered as 4-MeO-α-PVP metabolite candidates showing significant changes (p < 0.00001 and fold change >2) between the two investigated groups. Targeted LC-MS/MS analysis was conducted focusing on these significantly expressed features. Assisted by chemical formula determination according to high mass accuracy and in silico MS 2 fragmentation prediction, 19 chemical structure identifications were achieved. Among which, 8 metabolites have been reported derived from 4-MeO-α-PVP in a previous literature while 11 novel 4-MeO-α-PVP metabolites were identified by using our strategy. Further in vivo animal experiment confirmed that 18 compounds were 4-MeO-α-PVP metabolites, which demonstrated the feasibility of our strategy for screening the 4-MeO-α-PVP metabolites. We anticipate that this procedure may support and facilitate traditional metabolism studies and potentially being applied for routine NPS metabolites screening.

The current approaches remain insufficient for measuring chicken egg spoilage or present analytical limitations. This study aimed to complement the existing analyses and identify novel markers using liquid chromatography-high resolution mass spectrometry-based foodomics strategies. In the discovery set, comparative untargeted metabolomics was utilized to identify marker candidates in microbially inoculated chicken eggs. Markers were annotated by spectral matching with authentic standards, experimental libraries, or in silico fragmentation. In the validation set, targeted metabolomics was employed to verify the markers in stored chicken eggs from five farms. Statistical differences at a p -value < 0.001 revealed increases in lactic and 3-hydroxybutyric acids and decreases in phosphocholine, LPE(O-18:1), LPC(16:0), and LPC(18:0) in stored eggs. Receiver operating characteristic curve analysis of the six combined markers yielded an AUC of 0.956 and a sensitivity and specificity of ∼90%. Four phospholipids were highlighted as a novel class of spoilage markers. Our findings may contribute to further industrial implementation, benefiting the quality assurance and food safety of poultry egg production.

Purpose: Plasma markers that enable diagnosis in the early stage of lung cancer is not discovered. A liquid chromatography multiple reaction monitoring-mass spectrometry (LC-MRM-MS) assay for identifying potential early marker proteins for lung adenocarcinoma is developed., Experimental Design: LC-MRM-MS assay is used for measuring the level of 35 candidate peptides in plasma from 102 lung adenocarcinoma patients (including n = 50, 16, 24, and 12 in stage I, II, III, and IV, respectively.) and 84 healthy controls. Stable isotope labeled standard peptides are synthesized to accurately measure the amount of these proteins., Results: Seven proteins are able to distinguish stage I patients from controls. These proteins are combined in to a protein marker panel which improve the sensitivity to discriminate stage I patients from controls with cross-validated area under the curve = 0.76. Besides, it is found that low expression of eukaryotic initiation factor 4A-I and high expression of lumican show significantly poor prognosis in overall survival (p = 0.012 and 0.0074, respectively), which may be used as prognostic biomarkers for lung cancer., Conclusions and Clinical Relevance: Proteins highlighted here may be used for early detection of lung adenocarcinoma or therapeutics development after validation in a larger cohort., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)