Efficient preparation of a set of potential glycosidase inhibitors

May 29, 2012

(Phys.org) -- 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 screening of this library. As the scientists report in the , 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 . 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 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.

Explore further: Cell imaging gets colorful

More information: Herman S. Overkleeft, Synthesis of Eight 1-Deoxynojirimycin Isomers from a Single Chiral Cyanohydrin, European Journal of Organic Chemistry, dx.doi.org/10.1002/ejoc.201200377

Related Stories

New compounds for molecule interferometry experiments

Jul 20, 2011

When waves meet, a new single wave is created. This phenomenon is well understood for mechanical waves such as sound, and electro-magnetic waves such as light, and the "interference" of light waves is applied ...

Recommended for you

Cell imaging gets colorful

42 minutes ago

The detection and imaging of protein-protein interactions in live cells just got a lot more colourful, thanks to a new technology developed by University of Alberta chemist Dr. Robert E. Campbell and his ...

New strategy to combat 'undruggable' cancer molecule

42 minutes ago

Three of the four most fatal cancers are caused by a protein known as Ras; either because it mutates or simply because it ends up in the wrong place at the wrong time. Ras has proven an elusive target for ...

Chemists find a way to unboil eggs

2 hours ago

UC Irvine and Australian chemists have figured out how to unboil egg whites – an innovation that could dramatically reduce costs for cancer treatments, food production and other segments of the $160 billion ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.