Science Concentrates SYNTHESIS
Robust route for carbonyl-olefin metathesis Iron catalyst spurs synthesis of five-membered rings When organic chemists want to construct six-membered carbon rings, their go-to method is that old stalwart, the Diels-Alder reaction. But when they want to make five-membered rings, the route is less obvious.
toire. “It’s easy to do. You don’t need fancy reagents. You can do it in air,” she says. Also the transformation can produce a wide variety of five-membered, and even some six-membered, rings. Although carbonyl-olefin metathesis
[Fe] O FeCl3
O
O
O +
O O
O
O
Put a ring in it
O
A new carbonyl-olefin ring-closing metathesis reaction creates complex five-membered rings with just a catalytic amount of iron. Chemists at the University of Michigan, Ann Arbor, now report a carbonyl-olefin ring-closing metathesis reaction catalyzed by iron that creates such pentagonal structures with ease. The reaction, says chemistry professor Corinna S. Schindler, who spearheaded the work, has the potential to become a classic reaction in the organic chemist’s reper-
reactions—in which a C=O bond and a C=C bond switch bonding partners to make a new carbonyl and a new olefin—have been known for decades, most require stoichiometric amounts of transition-metal reagents, which adds to the cost and environmental impact of the transformation. The new reaction developed by Schindler, along with Jacob R. Ludwig, Paul M. Zim-
merman, and Joseph B. Gianino, requires only a catalytic amount of an inexpensive and abundant iron chloride catalyst (Nature 2016, DOI: 10.1038/nature17432). It also tolerates functional groups, such as amides and esters, and can even be used to construct rings that contain quaternary carbons—a challenging synthetic motif. The researchers believe the reaction proceeds through an oxetane intermediate that’s coordinated to iron from the FeCl3 catalyst. To verify this metathesis mechanism, Zimmerman, a chemistry professor who specializes in computation, used a reaction discovery method he developed called ZStruct. “We theoretically investigated several thousand possible reaction paths,” he says. The analysis suggested the oxetane mechanism was the most likely because it had the lowest energy barrier of the bunch. “This work represents a major development in the area of carbonyl-olefin metathesis,” comments Tristan H. Lambert, a chemist at Columbia University, who works on metathesis chemistry. “The Schindler group has taken a significant leap forward in demonstrating catalysis and ring-closing carbonyl-olefin metathesis on a much broader range of substrates than in previous work.”—BETHANY HALFORD
BIOCHEMISTRY
Prion proteins have a notorious reputation. These types of proteins can fold into conformations that coax other prions to join them, leading to the formation of insoluble protein aggregates. This is the mechanism behind some neurodegenerative diseases such as Creutzfeldt-Jakob, mad cow, and maybe Alzheimer’s disease. But not all prions are bad. In the past decade, researchers have found that some organisms, such as yeast, flies, and even mammals, use prions’ self-propagating clumping as part of normal cellular functions. Now, a team of scientists reports the first protein in plants that exhibits prion behavior (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1604478113). The findings provide further evidence that prions are more than just disease-causing abnormalities of the protein world.
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C&EN | CEN.ACS.ORG | MAY 2, 2016
Susan Lindquist of the Whitehead Institute for Biomedical Research and colleagues looked at suspected prion domains in three proteins from the flowering plant Arabidopsis thaliana. To test for prion behavior, the team replaced the prion domain of a well-studied yeast protein, Sup35, with the suspected prion domains of each of the candidates. Once inserted into yeast, the candidate domain from the flowering protein luminidependens acted like Sup35, showing that the plant protein could behave like a prion in yeast. Lindquist says researchers still need to show that the protein acts like a prion in the plant itself. The team hypothesizes the prion might play a role in helping the plant determine when to flower by storing information about the length of winters, a process called vernalization.
Arabidopsis thaliana may contain the first known plant prion. But plant molecular biologist Scott Michaels of Indiana University, Bloomington, points out that although luminidependens helps regulate flowering, it is not involved in vernalization pathways. Still, he thinks the work raises an interesting question of how the plants might rely on the prion mechanism. According to Lindquist, the findings demonstrate how prion behavior can be found in many organisms. “Prions are famous for how bad they can be,” she says. “We really need to open our eyes and see that they’re not just bad things and look for them in other places.”—MICHAEL TORRICE
CREDIT: DAWID SKALEC/WIKIPEDIA
First plant prion reported
