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
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy