Science Concentrates CATALYSIS
NATURAL PRODUCTS
▸ Triple adamantane expands the boundary of phosphine ligands
Complex construction via radical cascade Ophiobolin sesterterpenes are a family of fungal metabolites that have been shown to have cancer-killing properties, even against the drug-resistant brain tumor glioblastoma multiforme. As targets for total synthesis, they pose plenty of challenges for organic chemists: They’re packed with stereocenters and feature a 5-8-5 H O O H fused ring system that’s tough to construct. Previous efforts have produced ophiobolin A H in 47 steps and ophiobolin C in 38 steps. Chemists at the University of California, Berkeley, H H have now managed to make another family (–)-6-epi-Ophiobolin N member, (–)-6-epi-ophiobolin N, in just nine steps, starting from farnesol (Science 2016, DOI: 10.1126/science.aaf6742). The key process in the synthetic route, developed by Thomas J. Maimone, Zachary G. Brill, and Huck K. Grover, is a radical cascade reaction that knits together the 5-8-5 fused ring system. When the researchers first tried this radical reaction, they found it gave them a mix of stereoisomers at one carbon, with the majority of the product having the undesired stereochemistry. After some trial and error, they found that addition of a complex thiol could shift the stereochemical outcome to produce more of the desired product. The researchers say this work lays the foundation for forging other complex ring systems that could benefit total syntheses.—BETHANY HALFORD
building blocks important for the origin of who led the research team (Sci. Adv. 2016, life. The work follows the prior discovery of DOI: 10.1126/sciadv.1600285). Glycine was organic molecules on 67P, including methyl detected on several occasions by a mass isocyanate, acetone, propanal, and spectrometer called ROSINA on O acetamide. In total, the findings the Rosetta probe as it orbited and NH2 support the theory that comet imapproached the comet for landing HO pacts may have played a crucial role in 2014. The team believes the Glycine in seeding life on our planet, notes measured glycine was released the University of Bern’s Kathrin Altwegg, from dust grains in 67P’s coma, the hazy envelope that surrounds a comet. Although glycine was previously found in a sample taken from the Wild 2 comet, that sample had some contamination issues, leaving glycine’s cometary origin to be inferred by carbon isotope ratios. With 67P, Rosetta measured the amino acid’s presence at the comet directly, avoiding possible contamination issues back on Earth.—SARAH
EVERTS
ASTROCHEMISTRY
▸ Glycine and phosphorus found on comet Data from the European Space Agency’s Rosetta mission reveal that the comet 67P/Churyumov-Gerasimenko is home to glycine and phosphorus, two biological
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C&EN | CEN.ACS.ORG | MAY 30, 2016
DRUG DEVELOPMENT
▸ Designing troublefree estrogens Researchers have measured glycine on the comet 67P/Churyumov-Gerasimenko, adding support to the idea that comets could have helped kick-start life on Earth.
For postmenopausal women or for women who have had surgery to remove their ovaries, estrogen replacement therapy can help smooth out hot flashes, depression, weight
CREDIT: ESA
Phosphine ligands have played a supporting role in the success of many a transition-metal catalyst, helping to tune their activity, selectivity, and stability. Among the examples, tri(tert-butyl)phos+ phine has long been characterized as the most electron-reP leasing alkylphosH phine ligand for Pd metals. Liye Chen, O Peng Ren, and N Brad P. Carrow of H Princeton UniverTri(1-adamantyl)phosphine sity have succeeded palladium catalyst in raising the bar with tri(1-adamantyl)phosphine, PAd3, a ligand that now provides a bridge between trialkylphosphines and the stronger electron-releasing N-heterocyclic carbene ligands (J. Am. Chem. Soc. 2016, DOI: 10.1021/ jacs.6b03215). Adamantane is an unusual rigid C10 tricyclic alkane. Researchers have made phosphine ligands containing two adamantyl groups before, and adamantane is occasionally used as a bulky substituent for N-heterocyclic carbenes. But installing a third bulky adamantyl group on phosphorus has been a challenge, one that researchers took on with complex approaches. Carrow’s group pulled it off with a simple substitution reaction between commercially available HPAd2 and AdCO2CH3. The researchers demonstrated the utility of the surprisingly stable PAd3 by forming the palladium catalyst shown above and using it for Suzuki-Miyaura couplings, including using chlorinated heteroarenes to make drug intermediates and derivatives, with good results.—STEVE RITTER
gain, and other side effects stemming from abnormal hormone levels. But taking an estrogen supplement doesn’t come without side effects, such as increased risk of breast and uterine cancer. Researchers led by Benita S. Katzenellenbogen and John A. Katzenellenbogen of the University of Illinois, Urbana-Champaign, have a possible solution with a set of “pathway preferential” estrogen analogs they have developed (Sci. Signal. 2016, DOI: 10.1126/scisignal. aad8170). When estrogens bind to estrogen receptors, they trigger a set of biochemical pathways. The exOH tranuclear signaling pathway, which involves a transient estrogen binding HO process, helps control metabolism Estradiol in adipose tissue OH and in the liver to reduce fat accumulation and repair blood vessels. The nuclear signaling HO pathway, which requires sustained PaPE-1 estrogen analog estrogen binding, stimulates activity in reproductive and breast tissue, including the proliferation of cancer cells. The Katzenellenbogens and their team designed estrogen analogs, such as PaPE-1 (shown), that preserve the essential chemical features of estrogens but reduce estrogen receptor binding affinity. Working with mice, the researchers found that the analogs trigger the extranuclear pathway but don’t bind strongly enough to sustain the nuclear pathway, providing potentially trouble-free options for hormone replacement therapy.—STEVE RITTER
CREDIT: SHUTTERSTOCK (MUNG BEANS); LANGMUIR (SCHEMATIC)
IONIC LIQUIDS
▸ Liquid salts selforganize beyond expectations Like Paul McCartney, researchers studying ionic liquids have found wisdom in three simple words: Let it be. Ionic liquids are viscous fluids made of salts that are unable to crystallize at or near room temperature. Despite their inability to package themselves into solids, ions within the liquids can arrange themselves into orderly fluid layers near interfaces, for in-
NANOMATERIALS
Zinc oxide particles could amount to a hill of beans Plants need phosphorus. But they typically can’t process the entire dose of phosphorus-rich fertilizer farmers apply before the nutrient washes away or mineralizes into inconsumable forms. Researchers led by Ramesh Raliya and Pratim Biswas of Washington University in St. Louis have developed a zinc oxide nanoparticle aerosol spray that boosts the ability of mung bean plants to mobilize and better use phosphorus in the soil so less goes to waste (J. Agric. Food Chem. 2016, DOI: 10.1021/acs.jafc.5b05224). The team decided to study mung beans because they are Zinc oxide an important source of dietary protein in developing nanoparticles could and highly populated areas, especially in Asia. The help farmers grow researchers say the zinc oxide nanoparticles produce mung beans such similar effects in other crops as well. Plants absorb as these with less the nanoparticles through their leaves, and once fertilizer. inside the plant, the zinc accelerates the activity of phosphorus-mobilizing enzymes such as phytase and phosphatase, Raliya and Biswas explain. As a result, plants treated with the nanoparticles take up more phosphorus, produce more chlorophyll, and grow more voluminous roots. The researchers believe this technology will help farmers meet food demand while allowing them to use less fertilizer, which would reduce costs and the environmental impact of agricultural runoff.—MATT
DAVENPORT
stance between the liquid and air. These layers can stretch for dozens of nanometers, or so researchers believed. Radhika S. Anaredy and Scott K. Shaw of the University of Iowa have now discovered that ionic liquids can form micrometer-thick ordered layers, when researchers are patient (Langmuir 2016, DOI: 10.1021/acs. langmuir.6b00304). The Iowa chemists typically analyze interfaces in ionic liquids using infrared spectroscopy and other optical techniques as the materials ooze
down rotating, mirrored silver surfaces. But Anaredy and Shaw found that stopping the rotation and letting the liquid be for 10 to 30 minutes permitted the ions to self-organize into thicker layers. The duo is uncertain as to what drives the ordering, but Shaw says this discovery could help researchers use ionic liquids to design better capacitors for energy storage or proton-conducting solvents that help convert carbon dioxide into methane and other fuels.—MATT DAVENPORT
An example of time-dependent ordering of the negative charges in ionic liquids containing bis(trifluoromethylsulfonyl)imide anions, which orient themselves parallel to a surface. MAY 30, 2016 | CEN.ACS.ORG | C&EN
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