Community Research and Development Information Service - CORDIS

Novel approach for drug synthesis

Synthetic chemistry plays a key role in the preparation of new molecules that could serve as bioactive drugs. European researchers developed an innovative synthetic method for obtaining pure drug molecules of specified geometry.
Novel approach for drug synthesis
It is of vital importance to obtain the correct configuration of small molecules during drug synthesis as different mirror images often have diverse biological properties. In chemistry, the term chirality is used to describe compounds with superimposing geometry. To control which mirror image of the product is formed, scientists must determine the absolute configuration at the carbon atom. In turn, this requires the synthesis of carbon-carbon bonds in a controlled manner.

An important method to prepare carbon-carbon bonds is to remove a proton from a compound using a base and to react the metallated intermediate with an electrophile. Often, nitriles are used in such reactions since the cyano functional group they contain can give rise to many different classes of organic molecules and bioactive compounds. In addition, nitrile-containing compounds of diverse structure are present in many medicinal drugs. However, this approach yields mixtures of mirror images, posing a significant challenge to the chemistry community.

Scientists on the EU-funded ARNIIF (Asymmetric reactions of nitrile compounds: an approach to the synthesis of bioactive molecules) project wished to transfer the optical purity from the nitrile to the final product. In this context, they investigated whether it was possible to perform selective reactions with optically active metallated nitriles.

Researchers prepared different chiral nitriles and studied the rate at which the metallated mirror images interconverted. Following a thorough study of their structures and their capacity to undergo further transformations, they discovered highly selective reactions. These allowed the formation of products without significant loss of optical purity, culminating in the highly selective deprotonation of piperidine, a compound with a nitrile in the 2-position.

Overall, the deliverables of the ARNIIF project have the potential to be applied in the pharmaceutical industry for biomedical purposes. This is of great significance considering that currently more than 30 nitrile-containing pharmaceuticals are in the market for various medical indications.

Related information

Subjects

Life Sciences

Keywords

Synthetic chemistry, chirality, nitrile, ARNIIF, piperidine
Record Number: 200136 / Last updated on: 2017-06-29
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