We report Ni-catalyzed formal carboacylation of o-allylbenzamides with arylboronic acid pinacol esters. The reaction is triggered by oxidative addition of an activated amide C–N bond to a Ni(0) ...catalyst and proceeds via alkene insertion into a Ni(II)–acyl bond. The exo-selective carboacylation reaction generates 2-benzyl-2,3-dihydro-1H-inden-1-ones in moderate to high yields (46–99%) from a variety of arylboronic acid pinacol esters and substituted o-allylbenzamides. These results show that amides are practical substrates for alkene carboacylation via amide C–N bond activation, and this approach bypasses challenges associated with alkene carboacylation triggered by C–C bond activation.
Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. ...At a cellular and molecular level, adult plasticity is actively limited. Some of these "brakes" are structural, such as perineuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects.
•Dichoptic video game play improved acuity and stereopsis in amblyopic adults.•A control “supervised patching” group showed no improvement.•Contrast sensitivity and reading speed also improved for ...the game group.•This approach may have promise for the treatment of adult amblyopia.
Previous studies have employed different experimental approaches to enhance visual function in adults with amblyopia including perceptual learning, videogame play, and dichoptic training. Here, we evaluated the efficacy of a novel dichoptic action videogame combining all three approaches. This experimental intervention was compared to a conventional, yet unstudied method of supervised occlusion while watching movies.
Adults with unilateral amblyopia were assigned to either play the dichoptic action game (n=23; ‘game’ group), or to watch movies monocularly while the fellow eye was patched (n=15; ‘movies’ group) for a total of 40hours.
Following training, visual acuity (VA) improved on average by ≈0.14logMAR (≈28%) in the game group, with improvements noted in both anisometropic and strabismic patients. This improvement is similar to that obtained following perceptual learning, video game play or dichoptic training. Surprisingly, patients with anisometropic amblyopia in the movies group showed similar improvement, revealing a greater impact of supervised occlusion in adults than typically thought. Stereoacuity, reading speed, and contrast sensitivity improved more for game group participants compared with movies group participants. Most improvements were largely retained following a 2-month no-contact period.
This novel video game, which combines action gaming, perceptual learning and dichoptic presentation, results in VA improvements equivalent to those previously documented with each of these techniques alone. Our game intervention led to greater improvement than control training in a variety of visual functions, thus suggesting that this approach has promise for the treatment of adult amblyopia.
Abnormal visual experience during a sensitive period of development disrupts neuronal circuitry in the visual cortex and results in abnormal spatial vision or amblyopia. Here we examined whether ...playing video games can induce plasticity in the visual system of adults with amblyopia. Specifically 20 adults with amblyopia (age 15-61 y; visual acuity: 20/25-20/480, with no manifest ocular disease or nystagmus) were recruited and allocated into three intervention groups: action videogame group (n = 10), non-action videogame group (n = 3), and crossover control group (n = 7). Our experiments show that playing video games (both action and non-action games) for a short period of time (40-80 h, 2 h/d) using the amblyopic eye results in a substantial improvement in a wide range of fundamental visual functions, from low-level to high-level, including visual acuity (33%), positional acuity (16%), spatial attention (37%), and stereopsis (54%). Using a cross-over experimental design (first 20 h: occlusion therapy, and the next 40 h: videogame therapy), we can conclude that the improvement cannot be explained simply by eye patching alone. We quantified the limits and the time course of visual plasticity induced by video-game experience. The recovery in visual acuity that we observed is at least 5-fold faster than would be expected from occlusion therapy in childhood amblyopia. We used positional noise and modelling to reveal the neural mechanisms underlying the visual improvements in terms of decreased spatial distortion (7%) and increased processing efficiency (33%). Our study had several limitations: small sample size, lack of randomization, and differences in numbers between groups. A large-scale randomized clinical study is needed to confirm the therapeutic value of video-game treatment in clinical situations. Nonetheless, taken as a pilot study, this work suggests that video-game play may provide important principles for treating amblyopia, and perhaps other cortical dysfunctions.
ClinicalTrials.gov NCT01223716.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst is presented as a facile method for generating chiral benzylic boronate esters. Various vinylarenes ...react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities.
The nickel-catalyzed intermolecular carboacylation of alkenes with amides and tetraarylborates is presented. Bicyclic alkenes are readily functionalized with a variety of N-benzoyl-N-phenylbenzamides ...and triarylboranes, which are generated in situ from the corresponding tetraarylborates, to synthesize ketone products in up to 91% yield. Preliminary mechanistic studies suggest that migratory insertion precedes transmetalation and that reductive elimination is the turnover-limiting step. These reactions occur with excellent chemoselectivity and diastereoselectivity in the absence of a directing/chelating group and further demonstrate amides as practical acyl electrophiles for alkene dicarbofunctionalization reactions.
Enantioselective synthesis of polycyclic nitrogen, oxygen, and sulfur heterocycles by rhodium-catalyzed intramolecular alkene hydroacylation is reported. The intramolecular hydroacylation reactions ...generate 1,4-dihydrocyclopentabindol-3(2H)-ones and 3,4-dihydrocyclopentabindol-1(2H)-one in moderate-to-high yields (65–99%) with good-to-excellent enantioselectivities (84–99% ee). The catalyst system also promotes alkene hydroacylation of 3-vinylfuran-, 3-vinylbenzothiophene-, and 3-vinylthiophene-2-carboxaldehydes to generate the corresponding ketone products in moderate-to-high yields (71–91% yield) with excellent enantioselectivities (97–99% ee).
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