In many biological and pathological processes, glycosidase enzymes attack glycosidic bonds in carbohydrates, glycoproteins, and glycolipids. The ability to modify or block these processes by specific glycosidase inhibitors forms the basis for their potential use in the treatment of viral infections, cancer, and genetic disorders.
A Dutch team led by Herman S. Overkleeft has now developed a method that allows the synthesis of 8 of the 16 possible configurational isomers of the inhibitor candidate deoxynojirimycin, which will allow comprehensive medicinal chemistry screening of this library. As the scientists report in the European Journal of Organic Chemistry, their technique requires the use of a common precursor to prepare all eight compounds of biological interest.
Deoxynojirimycin and its derivatives have been long pursued by organic and medicinal chemists as a result of their potential as glycosidase inhibitors. Many groups now pursue these compounds for their application in the treatment of genetic disorders and type II diabetes. Consequently, many synthetic studies on deoxynojirimycins have appeared and continue to appear; however, synthetic strategies that allow different configurational isomers to be prepared in a concise fashion are scarce.
This synthesis of such a library is important so that the compounds can be studied side by side. This technique can give chemists important insight into which structural features lead to higher levels of biological activity.
The scientists' procedure involves the use of a common cyanohydrin as the starting material, which is easily accessible in large quantities. The cyanohydrin is then transformed into cyclic building blocks from which the individual isomers can be assembled by using typical organic transformations. This work complements the large body of literature on the synthesis of 1-deoxynojirimycin derivatives with the distinguishing feature that eight stereoisomers of this important class of glycosidase inhibitors can be derived from a common precursor in an efficient manner. This team is therefore well on its way to helping scientists screen a diverse range of potential drugs that may lead to the treatment of important diseases.Author: Herman S. Overkleeft, Universiteit Leiden (The Netherlands), http://biosyn.lic.leidenuniv.nl/people/overkleeft
European Journal of Organic Chemistry, Permalink to the article: http://dx.doi.org/10.1002/ejoc.2012003
Herman S. Overkleeft | Wiley-VCH
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