Andy Murray in Emery out camp, claims Mourinho would have been great for Arsenal

first_img 1 Pressure is growing on Unai Emery after a poor start to the season ‘Andy Murray: Resurfacing’ will launch exclusively on Amazon Prime Video on Friday Getty Images – Getty The three-time Gland Slam champion also claims Arsenal may have made a fault by not bringing in Jose Mourinho.Mourinho, of course, now holds court across north London, having been drafted in by Tottenham as a wildcard replacement for Mauricio Pochettino last week.“I love it when he’s in the Premier League”, Murray said of Mourinho, who is a big tennis fan and admitted earlier this year that the Brit’s first Wimbledon triumph reduced him to tears.“I just think he makes it so much more interesting to be honest.“I think he would do a good job for Arsenal.“The one thing about him is that you know he will win. He finds ways to win matches, tournaments.“That would have been a great appointment.”Murray was speaking to talkSPORT ahead of the release of a new Amazon documentary, charting his remarkable return from injury.The 32-year-old feared he would have to retire at the start of the year due to a chronic hip injury, but is now back playing at the top level again and is set to make his Grand Slam return at the Australian Open in January. Sir Andy Murray reckons it could be game, set and match for Unai Emery at Arsenal.Emery is at break point having overseen just two wins in 11 Premier League games and Murray, a Gunners fan, believes it may be time to serve the Spaniard his notice.“I actually haven’t been to the ground this season,” said Murray. “But from what I’ve been reading the atmosphere has been pretty bad – and I don’t think that’s good news for the players, staff or anyone there.“Unless that changes quickly, a change has to be made.” Raw. Emotional. Inspiring.It’s @andy_murray like you’ve never seen him before.Resurfacing. Coming to #PrimeVideo on Friday 29 November. pic.twitter.com/cVWVRSE9DD— Amazon Prime Video Sport (@primevideosport) November 25, 2019last_img read more

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Researchers provide evidence for a nonenzymatic pathway to produce paracaseolide A

first_img Explore further Isolation chemists have proposed that paracaseoline A arose through a Diels Alder [4+2] cycloaddition of an alpha-alkenylbutenolide. In all of these studies the researchers completed both the Diels-Alder cycloaddition and dehydration reaction in a single operation under harsh conditions (110oC). The assumption was that the initial dimerization proceeded via an endo transition state geometry. The harsh conditions that were required to complete this process gave rise to the idea that there is a naturally-occurring enzyme in the mangrove plant to catalyze this dimerization (a Diels-Alderase).Wang and Hoye report that the dimerization of the alkenylbutenolide precursor can occur through milder conditions than the typical 110oC reported in the literature and that the precursors interact through an exo orientation rather than the reported endo orientation. This means that in order to arrive at the relative configuration of the natural product, one of the carbon atoms undergoes an epimerization. Wang and Hoye provide compelling evidence that this epimerization occurs through a keto-enol tautomerization and subsequent interaction with the solvent.To prove that the cycloaddition occurs through an exo transition state, Wang and Hoye first investigated an analog to paracaseolide A that has shortened methyl chains rather than the dodecyl alkyl chains. After verifying that their synthetic analog behaved similarly to the naturally-occurring paracaseolide A under the harsh synthetic conditions mentioned in the literature, they tested whether they could obtain product using milder conditions. They were able to isolate the exo Diels-Alder adduct (pre-dehydration intermediate) by reacting the butenolide precursor at 35oC, neat, for six days. The authors verified that it was the Diels-Alder adduct using X-ray crystallography. They also verified that the dimerization step must have proceeded through an exo orientation. DFT studies showed that the transition state leading to the exo Diels-Alder adduct was lower in energy than that of the endo transition state. Furthermore, tests in which the alkyl truncated analog and the analogous Diels-Alder adduct with the dodecyl alkyl chains in place (which could also be formed under ambient conditions) were mixed showed that the reaction via the exo pathway is not reversible.Wang and Hoye believe that the exo adduct is preferred over the endo adduct because the geometry of lowest energy transition state is C2-symmetric. The product is formed through a pathway known as a bis-pericyclic process, passing through a transition state in which the two possible modes of cycloaddition [4+2] and [2+4] have merged. This kind of C2-symmetric, bis-pericyclic assembly has been proposed to be operative in the formation of other simpler compounds and to account for their stereochemistry (e.g., dicyclopentadiene), but not for a natural product, here paracaseolide A.Since one of the four fused rings in the isolated exo adduct is open (a keto acid), Wang and Hoye explored whether reaction through the ring-opened tautomer of the precursor hemiacylal was a possible route for the naturally occurring synthesis. It turns out that this route may be a possibility as it also yields an exo analog for its product. Finally, optical studies suggest that naturally occurring paracaseolide A is racemic just as the synthetic product is. If this is the case, then the naturally occurring reaction likely did not proceed via an enzymatic pathway. Enzymes typically produce an excess of one enatiomer.All of these experiments provide evidence that naturally occurring paracaseolide A is likely formed through a different reaction mechanism than what has been presented in the published literature. The synthesis of paracasolide A does not have to proceed via dimerization under harsh conditions producing an endo Diels-Alder adduct, but likely proceeds through a bis-pericyclic [4+2] dimerization. The mild nature of the conditions required for the dimerization as well as the racemic nature of the naturally produced paracaseolide A are consistent with the proposition that this spontaneous dimerization occurs in nature and that dimerization does not require catalysis by a Diels-Alderase enzyme. Journal information: Nature Chemistry Citation: Researchers provide evidence for a non-enzymatic pathway to produce paracaseolide A (2015, July 14) retrieved 18 August 2019 from https://phys.org/news/2015-07-evidence-non-enzymatic-pathway-paracaseolide.html Researchers achieve enzyme-catalyzed Diels-Alder reaction More information: “Diels-Alderase-free, bis-pericyclic, [4+2] dimerization in the biosynthesis of (+/-)-peracaseolide A” Tao Wang and Thomas R. Hoye, Nature Chemistry, DOI: 10.1038/nchem.2281AbstractThe natural product paracaseolide A is a tetracyclic dilactone containing six adjacent stereocentres. Its skeleton occupies a unique structural space among the >200,000 characterized secondary metabolites. Six different research groups have reported a chemical synthesis of this compound, five of which used a thermal, net Diels–Alder [4+2] cycloaddition and dehydration at 110 °C to access the target by dimerization of a simple butenolide precursor. Here, we report that this dimerization proceeds under much milder conditions and with a different stereochemical outcome than previously recognized. This can be rationalized by invoking a bis-pericyclic transition state. Furthermore, we find that spontaneous epimerization, necessary to correct the configuration at one key stereocentre, is viable and that natural paracaseolide A is racemic. Together, these facts point to the absence of enzymatic catalysis (that is, Diels–Alderase activity) in the cycloaddition and strongly suggest that a non-enzyme-mediated dimerization is the actual event by which paracaseolide A is produced in nature. © 2015 Phys.org (Phys.org)—Paracaseolide A is a naturally occurring compound found in the Chinese mangrove plant (Sonneratia paracaseolaris). Among its abilities, it inhibits an important enzyme in the cell cycle progression and affects regulation of the insulin pathway. What is perhaps most fascinating about this compound is its structure. Tao Wang and Thomas R. Hoye from the Department of Chemistry at the University of Minnesota provide compelling evidence that paracaseolide A proceeds via a different reaction mechanism that what has been reported by several groups in the literature. Specifically, they test whether the reaction proceeds via the spontaneous dimerization of a hydroxybutenolide precursor. Their work appears in Nature Chemistry. Structure and previous syntheses of paracaseolide A. Credit: Tao Wang & Thomas R. Hoye, Nature Chemistry (2015) doi:10.1038/nchem.2281 This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.last_img read more

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