A research group led by Dr. Kazuaki Ishihara, a professor at Nagoya University, has established a new method of chemically modifying ketones in a way that ensures that optically active cyanohydrins are obtained, enabling efficient production of pharmaceutical precursors at a high yield and with good selectivity.
In the production of pharmaceuticals, it is extremely important to produce molecules that have the right kind of symmetry. Even products that have the same composition, but are mirror images of each other, can have different effects in the body.
Considerable interest has been generated by a recent advance made by scientists at Nagoya University, which was reported online in the journal Angewandte Chemie. Specifically, these researchers managed to modify molecules called ketones by adding new chemical groups in a way that produces more of a single mirror image of the same type of molecule.
This study extends previous work on modifying ketones to produce cyanohydrins, which are useful molecules because they are precursors of carboxylic acids and some amino acids, which are the building blocks of life. The similarity of cyanohydrins and their derivatives to amino acids means that they have important pharmaceutical properties.
However, in previous studies, the modification of ketones to produce cyanohydrins was inefficient, time-consuming, could only produce a small amount of desired product, and was only available for a narrow range of compounds.
These obstacles have now been overcome by an innovative new reaction. “Using a new catalyst, chiral lithium(I) phosphoryl phenoxide, we have been able to add a cyano group with excellent enantioselectivity on ketones using lithium dicyanotrimethylsilicate(IV),” says Dr. Manabu Hatano, an associate professor and the first author. “This reaction had a high yield despite only a weak Lewis acid catalyst being used.”
Previous studies in which efforts were made to produce optically active cyanohydrins encountered difficulties when using ketones rather than aldehydes as the molecules to be cyanosilylated because they are less reactive. This was overcome by the new approach, which was demonstrated by synthesizing a key intermediate for the production of (+)-13-hydroxyisocyclocelabenzine, a pharmaceutical that has antibacterial and antitumor effects.
“Another advantage of our new method is that the reaction time is much shorter, lasting only 2 to 9 hours rather than 1 to 2 days,” according to Katsuya Yamakawa, another member of the research team. “This would be helpful in the pharmaceutical industry when attempting to produce the desired products on a large scale for medical use.”
After the demonstration of this new catalytic system in a large-scale reaction, it is hoped that it can be applied widely for more effective cyanosilylation, enabling cheaper and more accurate production of pharmaceutical products.
The article “Enantioselective Cyanosilylation of Ketones with Lithium(I) Dicyanotrimethylsilicate(IV) Catalyzed by a Chiral Lithium(I) Phosphoryl Phenoxide” was published online in Angewandte Chemie, at doi: 10.1002/anie.201510682
Angewandte Chemie, at doi: 10.1002/anie.201510682
Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine
New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
26.06.2017 | Life Sciences
26.06.2017 | Physics and Astronomy
26.06.2017 | Information Technology