Aryl fluorides are widely used in the pharmaceutical and agrochemical industries, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C-H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood-brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C-H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C-H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.
Abstract. The three-dimensional (3-D) form and the interrelationship of peroxisomes (Po) in the model of regenerating rat liver after partial hepatectomy were studied by computer-assisted 3-D reconstruction of serial ultrathin sections. Po were labeled cytochemically for either catalase, which stains them all uniformly, or for D-amino acid oxidase (DAA-OX), which gives a heterogeneous reaction with lightly and darkly stained PO. In regenerating rat liver, Po exhibit marked pleomorphism with some budding forms and dumbbellshaped ones. The 3-D reconstruction revealed many single spherical Po measuring 0.15-0.8 l~m in diameter. In addition, two to five Po were found interconnected with each other via narrow 30-50-nm hourglass-shaped bridges forming a reticulum. Such aggregates of Po measured 1.5-2.5 Ixm across. Whereas all segments of this reticulum stained homogeneously for catalase, they exhibited a marked difference in the intensity of the DAA-OX reaction. These observations are consistent with the view of peroxisomal proliferation by budding or fragmentation from preexisting ones. Under such conditions of rapid growth as in regenerating liver, Po may be interconnected forming a reticulum. The interconnections between Po with differing DAA-OX activities suggest that they originate from the same parent organelle.
In addition to cerebellar disorders, SSCN patients suffer from severe peripheral vestibular dysfunction, which can exacerbate the patient's imbalance. When otolaryngologists encounter patients with distinctly progressive sensorineural hearing loss and imbalance, they should include SSCN in the differential diagnosis and perform neuro-otological examinations, including an electronystagmography recording and vHIT and brain magnetic resonance imaging.
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