The asymmetric α-chlorination
of activated aryl acetic acid
esters can be carried out with high levels of enantioselectivities
utilizing commercially available isothiourea catalysts under base-free
conditions. The reaction, which proceeds via the in situ formation
of chiral C1 ammonium enolates, is best carried out under cryogenic
conditions combined with a direct trapping of the activated α-chlorinated
ester derivative to prevent epimerization, thus allowing for enantioselectivities
of up to e.r. 99:1.
Systemic sclerosis (SSc) is a rare systemic autoimmune disorder marked by high morbidity and increased risk of mortality. Our study aimed to analyze metabolomic profiles of plasma from SSc patients by using targeted and untargeted metabolomics approaches. Furthermore, we aimed to detect biochemical mechanisms relevant to the pathophysiology of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry technology. The investigation of plasma samples from SSc patients (n = 52) compared to a control group (n = 48) allowed us to identify four different dysfunctional metabolic mechanisms, which can be assigned to the kynurenine pathway, the urea cycle, lipid metabolism, and the gut microbiome. These significantly altered metabolic pathways are associated with inflammation, vascular damage, fibrosis, and gut dysbiosis and might be relevant for the pathophysiology of SSc. Further studies are needed to explore the role of these metabolomic networks as possible therapeutic targets of SSc.
Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.
We report on the manufacture of a state-of-the-art heterogeneous non-noble metal catalyst, which is based on a molecularly well-defined phosphine-tagged cobalt corrole complex. This precursor compound is readily synthesized from convenient starting materials while the active material is obtained through wet-impregnation of the pertinent metalliferous macrocycle onto carbon black followed by controlled pyrolysis of the loaded carrier material under an inert gas atmosphere. Thus, the obtained composite was then applied in the heterogeneous hydrogenation of various nitroarenes to yield a vast array of valuable aniline derivatives that were conveniently isolated as their hydrochloride salts. The introduced catalytic protocol is robust and user-friendly with the entire assembly of the reaction set-up enabling the conduction of the experiments on the laboratory bench without any protection from air.
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