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DENYING SUGAR TO PROTEINS HAS THERAPEUTIC EFFECTS
COOKING UP CHIRAL ALLENES
J. AM . CHEM . SO C.
GOLDEN RING WITH AESTHETIC APPEAL Metal-oxygen-metal linkages in organometallic complexes underpin many applications in heterogeneous catalysis and in electro-optical and magnetic applications. But little is known about less common metal-carbon-metal linkages and the role they might play in catalysis and electronics. In a bid to learn more, Anthony F. Hill and coworkers at Australian National University have been exploring the synthesis of metallacarbyne complexes of the type LnM≡C–M´L´n, where M represents different metals and L various ligands. They have now discovered that the reaction between a W≡C–Sn version of the complex and a gold reagent leads to an unprecedented tetrameric gold-carbon ring (J. This metallacarbyne complex could provide clues for creating new catalysts.
One chemist’s trash can be another’s treasure. Take the β-hydride elimination, which chemists are trained to suppress during transition-metal-mediated bond forH mations. A team at the University Pd catalyst, R C O chiral ligand of Texas, San Antonio, has R C C turned that thinking around OR´ CF3O2SO and is now using β-hydride H elimination to make chiral al- R, R´= various groups lenes (J. Am. Chem. Soc., DOI: 10.1021/ja401606e). These compounds, which have two consecutive double bonds in a carbon chain, appear in some liquid crystals and an antiulcer drug. But the drug O is a mixture of two isomers because pure P O O chiral allenes are hard to make. A handful of research groups are bucking convention and treating β-hydride eliminations as reactions in their own right, says Doug E. Chiral phosphite ligand Frantz, who led the research. But his lab’s transformation is the first example of an asymmetric version of the reaction. Ian T. Crouch and Robynne K. Neff developed chiral phosphite ligands to carry out the chemistry, which so far works best when starting with (E)-enol triflates. Those reagents are expensive to make, Frantz says, and his team is looking for ways around them. They plan to use the reaction to make libraries of allenes for Eli Lilly & Co.’s Open Innovation Drug Discovery program. They’re also partnering with chemical reagent supplier SigmaAldrich to make the phosphite ligands available for everyone.—CD Am. Chem. Soc., DOI: 10.1021/ja400128h). Hill says making the Au4C4 ring complex (shown) is very much a case of aesthetic appeal, as he doesn’t anticipate that the complex will have any direct application to catalysis or any interesting photophysical properties. However, monomeric versions of the gold carbyne might serve to expedite transfer of carbido groups from tin to palladium in a catalytic manner. “A long way down the line, it will be interesting to see if these carbyne complexes do indeed have a role to play in molecular electronics,” he adds.—SR
DNA DAMAGE LINKED TO ALZHEIMER’S Not only does amyloid-β, the hallmark biomolecule associated with Alzheimer’s disease, trigger an inflammatory response in the brain when it aggregates, it probably also increases nerve cell DNA damage, according to a report (Nat. Neurosci., DOI: 10.1038/nn.3356). Commenting on the study, Peter J. McKinnon, a geneticist at St. WWW.CEN-ONLINE.ORG
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Researchers have identified compounds that inhibit the enzymatic addition of the sugar fucose to proteins in mice, a process called fucosylation that plays a role in tumor progression, immunity, and inflammation (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1222263110). Nicole M. Okeley, Peter D. Senter, and coworkers at Seattle Genetics, Bothell, Wash., found the compounds by screening a library of fucose derivatives. Studies in mice show that one of the compounds, 2-fluorofucose, has anticancer and anti-inflammatory effects and enhances immunity. 2-Fluorofucose is the first compound shown to turn off fucosylation in living animals, suggesting possible therapeutic applications. It works in cells by inhibiting enzymes that add fucose to antibodies and other proteins. Among many possible effects of that inhibition is an enhanced antibody-based response to a vaccine. “We are evaluating this technology for potential clinical applications,” Senter says.—SB
DNA BREAKS Compared with untreated nerve cells (left), cultured nerve cells exposed to amyloid-𝛃 (right) display more DNA damage (green). Cell nuclei are blue, and nerve cell skeletons are red.
Jude Children’s Research Hospital, in Memphis, says it provides “new insights into how the Alzheimer’s-related factor may lead to cell loss and neurodegeneration associated with the disease.” A team led by Lennart Mucke of the University of California, San Francisco, measured breaks in the nerve cell DNA of normal mice and of mice engineered to produce human amyloid-β. The team found that the engineered mice had up to four times as many nerve cells containing damaged DNA in their brains as did normal
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mice. When the team gave the antiepilepsy drug levetiracetam to amyloid-positive mice for a month, levels of DNA damage in nerve cells decreased to those found in nonengineered mice. According to Mucke, amyloid-β seems to increase DNA damage by provoking abnormal nerve activity, something that FDA-approved levetiracetam suppresses.—LKW
WHAT HUNGRY MICROBES EAT UNDER THE SEA The cold, oxygen-free sediment at the bottom of the sea hosts a wealth of microbes. Many bacteria living there survive by metabolizing methane as a carbon source, and researchers had assumed that archaea did the same. But researchers led by geomicrobiologist Bo Barker Jørgensen at Aarhus University, in Denmark, have found evidence for something different: Archaea appear to dine on proteins lurking in the marine sediment (Nature, DOI: 10.1038/ nature12033). For their discovery, the team went fishing in the seafloor of a Danish bay. Using core samples, they extracted individual cells from four species of archaea. Sequencing the genome of these archaea they found genes for enzymes that are excreted from cells and can break down proteins, genes for di- and tripeptide transport machinery that delivers dinner back into the cell interior, and genes for enzymes inside the cell that break down amino acids. One of the archaea has enzymes to metabolize d-amino acids, suggesting that the microbe might be getting its proteins from peptidoglycans of bacteria living in the sediment. The finding changes our conception of the marine sedimentary carbon cycle, the researchers note, as it was previously assumed that bacteria are primarily responsible for organic matter recycling in sediments.—SE
MASS SPEC DISCOVERY PLATFORM TURNS UP NEW REACTIONS New chemical reactions are out there just waiting to be found, but the myriad possibilities need to be screened and optimized. A new reaction discovery and optimization platform called label-assisted laser desorption/ionization time-of-flight mass spectrometry accelerates the path from initial hit to a synthetically useful reaction, according to Sergey A. Kozmin of the Univer-
lysts may approach 90% selectivity. Marimuthu Pyrene Pyrene and colleagues believe the Siloxy Product Catalyst label label alkyne copper atoms still oxidize on the nanoparticle surMASS DISCOVERY A pathway for label-assisted faces. But light-induced mass spectrometry reaction discovery. localized surface plasmon resonance of the metalsity of Chicago and coworkers, who devellic copper core causes electron transfer to oped the process (Nat. Chem., DOI: 10.1038/ Cu–O bonds, weakening them and promotnchem.1612). The method involves mixing ing reduction back to metallic copper. The a pyrene-labeled reactant with other reacresearchers suggest the approach could be tants in the presence of various catalysts. used to tune the oxidation state of other The pyrene label enables photoionization nanoparticle catalysts with a plasmonic of the reaction product for mass spec analycore, such as gold or silver.—JK sis. To demonstrate the approach, the team subjected a pyrene-labeled siloxy alkyne BOOSTING REACTIVITY to 23 different reactants plus a control and 29 catalysts for a total of 696 experiments. AT THE β-POSITION The researchers identified two previously When chemists pick out reactive hot spots unknown benzannulation reactions. For on aldehydes and ketones, they generally example, reaction of the alkyne with isofocus on the electrophilic carbonyl carbon quinoline N-oxide in the presence of a silver or the α-carbon next door. The α-carbon catalyst yielded an oxime product. They can easily shed a proton and become nuused the screening platform again to opticleophilic thanks to its relationship with mize the reaction and found that it works the carbonyl. Such neighborliness doesn’t better with a gold catalyst.—CHA typically extend to the β-carbon just one atom further along, which generally is reILLUMINATING COPPER garded as being too unreactive in saturated systems. To do anything at the β-position, PROMOTES PROPYLENE most chemists aim to install a double bond OXIDE PRODUCTION between it and the α-carbon. David W. Propylene oxide is a commodity chemiC. MacMillan and his team at Princeton cal used to make polyurethane plastics. University have now found a way to diCommercial processes for epoxidation of rectly arylate the β-position of saturated propylene to propylene oxide use hazardaldehydes and ketones, opening up an easy ous reagents that chemists would like to path to more elaborate molecules (Science, avoid. One prospect for a catalyst is metalDOI: 10.1126/science.1232993). The chemists lic copper, which shows high selectivity for use an iridium-based photoredox catalyst forming propylene oxide O O in a vacuum. However, CN the copper tends to oxiIridium photoredox catalyst, H H amine organocatalyst dize and lose selectivity + under commercial reaction conditions. Looking CN CN for a way to preserve the Arene Aldehyde β-Aryl aldehyde metallic copper surface, Andiappan Marimuthu, Jianwen Zhang, in combination with an organocatalyst and Suljo Linic of the University of Michicontaining an amine. The latter forms an gan demonstrated that exposing the cataenamine with the aldehyde or ketone, which lyst to visible light can solve the problem then reacts with the photoredox catalyst to (Science, DOI: 10.1126/science.1231631). generate a radical. This species reacts with a Working with copper nanoparticles deposcyano aryl group, which then eliminates cyaited on silica in a packed-bed reactor, they nide. Hydrolysis of the amine catalyst finally found that illuminating the catalyst with generates a β-arylated aldehyde or ketone a broadband visible light source increases product. MacMillan’s group demonstrated selectivity for propylene oxide from 20% to the versatility of the reaction by using a 50%, although current processes that use broad range of aldehydes, ketones, and aryl acid catalysts or more expensive gold catagroups (one shown).—BH
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