The combination of transition‐metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with ...chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α‐aminonitriles and α‐aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α‐functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
The first enantioselective reductive cyanation and phosphonylation of secondary amides have been achieved by the combination of iridium with chiral thiourea catalysis. The protocol is highly efficient and enantioselective, providing a novel route for the synthesis of optically active α‐aminonitriles and α‐aminophosphonates from bench‐stable feedstocks.
We report herein that the Ir and CuI bis‐metal catalyzed reductive alkynylation of amides, a method that we developed previously, can be extended to 6‐, 7‐, and 8‐membered lactams. The catalytic ...reductive alkynylation of 6‐methyl‐2‐piperidinones and its 3‐benzyloxy derivative proceeded with 2.3:1 to 7:1 2,6‐trans/cis diastereoselectivities. The resulting piperidines were converted into alkaloids (±)‐solenopsin, (±)‐solenopsin A, and (+)‐julifloridine all in only one step. This two‐step approach to the alkaloids is much shorter and much efficient than the conventional multistep methods.
A procedure‐economical synthesis of 2,6‐trans‐substituted piperidine alkaloids is described. The method consists of Ir and Cu catalyzed reductive alkynylation of N‐benzyllactams and tandem catalytic hydrogenation‐hydrogenolysis.
The combination of transition‐metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with ...chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α‐aminonitriles and α‐aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α‐functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
The first enantioselective reductive cyanation and phosphonylation of secondary amides have been achieved by the combination of iridium with chiral thiourea catalysis. The protocol is highly efficient and enantioselective, providing a novel route for the synthesis of optically active α‐aminonitriles and α‐aminophosphonates from bench‐stable feedstocks.
The Vaska’s complex—tris(pentafluorophenyl)borane combination was found to be a highly efficient cooperative catalysis system for the hydrosilylative reduction of tertiary amides to yield amines ...under mild conditions. The reaction shows high chemoselectivity, tolerating halide, phenolyl, alkenyl, nitro, nitrile, ester, azido, ketone, and enone functional groups. For unsubstituted cyclohexanone carboxamide, two variations were established to achieve either catalytic concomitant reduction of the two carbonyl groups or selective reduction of the amide carbonyl. The protocol was applied to the efficient synthesis and late-stage modification of several pharmaceuticals and derivatives. Importantly, we showed that by simply prolonging reaction time to 24–28 h, the reaction can reach an exceptionally high efficiency with turnover number (TON) up to 9.8×10
6
and turnover frequency (TOF) up to 408,333 at a quite low catalyst loading of 0.00001 mol% (S/C (Ir) = 10,000,000).
The conversion of β-amido esters to β-enamino esters is an indispensable step for some synthetic approaches to alkaloids and related medicines. Known methods for such transformation are not only ...stepwise, but also proceed with low atom-efficiency. Herein, we report a direct and versatile approach that features the Ir-catalyzed chemoselective reduction of β-amido esters with 1,1,3,3-tetramethyldisiloxane (TMDS). In addition, a lack of some signals was observed in the 13C NMR spectra of some alicyclic β-enamino esters. This revealed a longstanding existing but being ignored phenomenon in the literature.
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In this study, several kinds of flexible protective materials sprayed with polyurea elastomers (hereinafter referred to as polyurea elastomer protective material) were adopted to meet the abrasion ...resistance requirement of hydraulic structures, and their abrasion resistances against the water flow with suspended load or bed load were studied systematically through tests. Natural basalt stones were adopted as the abrasive for simulation of the abrasion effect of the water flow with bed load, and test results indicate that the basalt stone is suitable for use in the abrasion resistance test of the flexible protective material. The wear process of the polyurea elastomer protective material is stable, and the wear loss is linear with the time of abrasion. If the wear thickness is regarded as the abrasion resistance evaluation factor, the abrasion resistance of the 351 pure polyurea is about twice those of pure polyurea with a high level of hardness and aliphatic polyurea, and over five times that of high-performance abrasion-resistant concrete under the abrasion of the water flow with suspended load. It is also about 50 times that of high-performance abrasion-resistant concrete under the abrasion of the water flow with bed load. Overall, the abrasion resistance of pure polyurea presented a decreasing trend with increasing hardness. Pure polyurea with a Shore hardness of D30 has the best abrasion resistance, which is 60 to 70 times that of high-performance abrasion-resistant concrete under the abrasion of the water flow with bed load, and has been recommended, among the five kinds of pure polyurea materials with different hardness, in anti-abrasion protection of hydraulic structures.
Patients with difficult weaning who undergo mechanical ventilation are more likely to be at risk of reintubation and the sequential use of oxygen therapy after extubation is a concern for clinicians. ...Therefore, the aim of the present study was to compare the effects of transnasal high-flow nasal cannula (HFNC) oxygen therapy and non-invasive positive-pressure ventilation (NIV) on respiratory mechanics in patients with difficult weaning.
The present study was a single-center, retrospective, observational study. Twenty-nine patients with difficult weaning off invasive mechanical ventilation from the Department of Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, from December 2018 to April 2021, were included. Within 48 h after extubation, alternate respiratory support with HFNC and NIV was provided. Relevant indicators were recorded after each support mode had been maintained for at least 60 min. These included esophageal pressure (Pes), gastric pressure (Pga), transdiaphragmatic pressure (Pdi), pressure-time product of Pes (PTPes), pressure-time product of Pga (PTPga), pressure-time product of Pdi (PTPdi), ratio of the PTPdi to the PTPes (PTPdi/PTPes), and ratio of the Pes to the Pdi (Pes/Pdi), diaphragmatic electromyogram (EMGdi), percentage of esophageal pressure coefficient of variation (CVes%),diaphragmatic electromyogram coefficient of variation (CVEMG),inspiratory time (Ti), expiratory time (Te) and respiratory cycle time (Ttot).
Of the 29 patients included, 22 were males and 7 were females age: 63.97±15.34 years, Acute Physiological and Chronic Health Estimation II (APACHE II) score: 18.00±5.63. The CVes% and the Pes/Pdi were significantly higher in patients with NIV than HFNC using 40 L/min, CVes%: 9 (-6, 20)
-7 (-23, 6) and Pes/Pdi: 0.17 (-0.1, 0.53),
-0.12 (-0.43, 0.08) (P<0.05). The remaining indicators were not statistically different.
The sequential NIV and HFNC can be tolerated in patients with such difficult weaning off mechanical ventilation after extubation, and more patients tend to choose HFNC subjectively. Compared with HFNC, NIV reduces the work of adjunctive respiratory muscle, but the patient's Pes dispersion is high when NIV is used, and it is necessary to pay attention to patient-ventilator coordination in clinical practice. We recommend alternating HFNC and NIV during the sequential respiratory therapy after extubation.
AIM:To study the diagnostic value of controlled attenuation parameter(CAP),evaluated by transient elastography,for liver steatosis in patients with chronic hepatitis B(CHB).METHODS:Eighty-eight ...patients with CHB were enrolled in this study.All of the patients were subjected to transient elastography to determine CAP.These patients also underwent liver biopsy in the same period.Using liver biopsy as a reference,we determined receiver operating characteristic(ROC)curves for different endpoints.Areas under the ROC curves(AUCs)were used to evaluate the diagnostic importance of CAP for liver steatosis in patients with CHB.RESULTS:A positive correlation was observed between the AUCs of CAP and liver pathological stage(r=0.582,P<0.05).CAP was not correlated with inflammation degree and fibrosis degree(r=-0.025,P>0.05;r=0.068,P>0.05).The mean CAP value at S0 was 209.59±41.25 dB/m,223.84±35.28 dB/m at S1,274.17±43.69 dB/m at S2,and 312.50±25.44dB/m at S3.CAP values among S0,S1,S2,and S3were significantly different(F=17.79,P<0.01).The AUC values for CAP were 0.711(0.592-0.870),0.868(0.748-0.989),and 0.974(0.922-1.026)for S1,S2,and S3,respectively.The optimal cut-off values were219.5,230.0,and 283.5 dB/m.CONCLUSION:CAP is a novel tool that can be used to assess the degree of steatosis.
Hepatic encephalopathy(HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, ...minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging(MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight ofthe increasingly important role of blood oxygen level dependent functional MRI.
Background： The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy （IgAN） are unclear. This study was designed to evaluate the ...efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods： It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan （80 mg/d） wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo （Group A）, 50 mg/d clopidogrel （Group B）, 20 mg/d leflunomide （Group C）, or 50 mg/d clopidogrel and 20 mg/d leflunomide （Group D）. The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results： The effects oftelmisartan combined with leflunomide on changes in proteinuria （0.36 95% confidence interval （CI） 0.18 0.55 g/d, P 〈 0.001）, in serum uric acid （76.96 95% CI 57.44-96.49 μmol/L, P 〈 0.001）, in serum creatinine （9.49 95% CI 6.54-12.44μmol/L, P 〈 0.001）, and in estimated glomerular filtration rate （-6.72 95% CI-9.46 to -3.98 ml.min -1. 1.73 m -2, p 〈 0.001） were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight （P 〉 0.05）.Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions： Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.
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