Many drugs are based on natural substances. Because it is usually difficult, if not impossible, to isolate these in sufficient quantities from plants or microorganisms, they must be synthesized in the laboratory.
This requires linking carbon atoms – with the right spatial orientation (stereochemistry) relative to each other. In the journal Angewandte Chemie, E. Peter Kündig and a team from the University of Geneva (Switzerland) have now introduced a palladium-catalyzed synthesis that allows them to produce indoline derivatives with the correct spatial arrangement.When synthesizing large, complex organic molecules, it is generally easier to make smaller individual pieces that can then be linked together to make the final product. The award of the 2010 Nobel Prize in chemistry to R. Heck, E. Negishi, and A. Suzuki for their work on palladium-catalyzed cross-coupling indicates the importance of methods for creating bonds between carbon atoms.
Another complication in the synthesis of natural products is that molecules with identical atomic compositions can have different spatial arrangements.
This results from the chirality of carbon centers: when carbon is bound to four different partners, these can be arranged in two different ways that are mirror images of each other (chirality). When two carbon atoms are coupled together, new chiral centers may be formed. Coupling reactions that selectively deliver products with the desired spatial arrangement are thus high on the chemist’s wish list.
Kündig and his co-workers have now made a breakthrough. They have developed a new synthesis for fused indolines, a class of materials that represent an important structural motif in many natural products and pharmaceuticals, including the tumor drug Vinblastin, the antirheumatic drug Ajmalin, and the neurotoxin strychnine. Indoline is a double-ring structure consisting of one aromatic six-carbon ring and a nitrogen-containing five-membered ring; in a fused indoline, the five-membered ring is fused with an additional five- or six-membered ring.
As a starting material, the researchers used a molecule in which the central five-membered ring is still open. One of the carbon atoms to be bound was activated through binding to a bromine atom. Cleavage of the bromine and a hydrogen atom leads to ring closure. This forms a chiral center; so two different spatial arrangements of the product are possible. Thanks to a new special palladium catalyst, the researchers were able to exclusively involve only one C–H bond (of two chemically identical ones) in the reaction. Their success stems form a bulky chiral ligand, known as an N-heterocyclic carbene, which is bound to the palladium atom. The special thing about this novel catalyst is that the selectivity is maintained even at the required high temperatures around 150 °C.Author: E. Peter Kündig, Université de Genève (Switzerland), http://www.unige.ch/sciences/chiorg/kundig/home
Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201102639
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research