Imines and carboxylic acids have been directly coupled using propylphosphonic acid anhydride and NEt(i-Pr)2 to give N-acyliminium ions, which were intramolecularly trapped with oxygen, nitrogen, ...sulfur, and carbon nucleophiles to provide a wide range of structurally diverse heterocycles.
The enantioselective intermolecular C2‐allylation of 3‐substituted indoles is reported for the first time. This directing group‐free approach relies on a chiral Ir‐(P, olefin) complex and Mg(ClO4)2 ...Lewis acid catalyst system to promote allylic substitution, providing the C2‐allylated products in typically high yields (40–99 %) and enantioselectivities (83–99 % ee) with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2‐allylation, rather than C3‐allylation followed by in situ migration. Steric congestion at the indole‐C3 position and improved π–π stacking interactions have been identified as major contributors to the C2‐selectivity.
An enantioselective C2‐allylation of 3‐substituted indoles is reported, providing C2‐allylated products with excellent regiocontrol. Experimental studies and DFT calculations suggest that the reaction proceeds via direct C2‐allylation with steric congestion at the indole‐C3 position and π–π stacking interactions identified as major contributors to the selectivity observed.
Oceanic cyanobacteria are the most abundant oxygen-generating phototrophs on our planet and are therefore important to life. These organisms are infected by viruses called cyanophages, which have ...recently shown to encode metabolic genes that modulate host photosynthesis, phosphorus cycling and nucleotide metabolism. Herein we report the characterization of a wild-type flavin-dependent viral halogenase (VirX1) from a cyanophage. Notably, halogenases have been previously associated with secondary metabolism, tailoring natural products. Exploration of this viral halogenase reveals it capable of regioselective halogenation of a diverse range of substrates with a preference for forming aryl iodide species; this has potential implications for the metabolism of the infected host. Until recently, a flavin-dependent halogenase that is capable of iodination in vitro had not been reported. VirX1 is interesting from a biocatalytic perspective as it shows strikingly broad substrate flexibility and a clear preference for iodination, as illustrated by kinetic analysis. These factors together render it an attractive tool for synthesis.
This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS).
A multidisciplinary panel ...conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.
For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4-8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H
O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end-expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS.
The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.
An efficient Ag(I)-catalyzed π-acid activation method for the cyclization of cyclic ketimine-tethered ynones is reported. Various nitrogen-containing scaffolds commonly found in bioactive alkaloids ...can be prepared in high yields, and the utility of the method is demonstrated by a formal synthesis of (±)-lasubine II and in a short total synthesis of (±)-indolizidine 209D.
The total synthesis of (±)-janoxepin, a novel antiplasmodial d-leucine derived oxepine-pyrimidinone-ketopiperazine isolated from the fungus Aspergillus janus, is described. The cornerstones of the ...synthetic route are pyrimidinone preparation, ring-closing metathesis, aldol introduction of the enamide, and dihydro-oxepine elaboration. This synthetic route proved very efficient for the formation of a number of janoxepin analogues, including dihydro-janoxepin and tetrahydro-janoxepin.
A one-pot protocol for the dearomatizing spirocyclization/cross-coupling of alkyne-tethered indoles/pyrroles is described. Mechanistic studies support a process by which palladium complexes generated ...in situ act as both π-acid and cross-coupling catalysts. Overall, this facilitates an efficient cascade process that enables the simultaneous preparation of synthetically challenging quaternary spirocyclic carbons and tetrasubstituted alkenes in a single operation.
Indolyl α‐diazocarbonyls can be selectively cyclized to give six distinct products through the careful choice of catalyst and reaction conditions. A range of catalysts were used, including complexes ...of RhII, PdII, and CuII, as well as SiO2, to promote diazo decomposition and subsequent cyclization/rearrangement through a range of mechanistic pathways.
Pick a catalyst: Indolyl α‐diazocarbonyls can be selectively cyclized to give six distinct products through the careful choice of the catalyst and reaction conditions. A range of catalysts were used, including complexes of RhII, PdII, and CuII as well as SiO2, to promote diazo decomposition and subsequent cyclization/rearrangement through a range of mechanistic pathways.
An efficient silver(I)-catalyzed method is reported for the synthesis of substituted indoles, most notably 5-hydroxy-derivatives, via π-acidic alkyne activation. Most methods for the preparation of ...indoles involve annulation of a benzene precursor, but the method reported herein is unusual in that pyrrole precursors are used. Density Functional Theory (DFT) studies suggest that these reactions proceed via initial activation of the pyrrole C-3 position before undergoing subsequent rearrangement, contradicting the conventional wisdom that pyrroles are more nucleophilic through C-2.
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