Nitrogen-15 isotope can trigger asymmetric autocatalytic reactions toward chiral organic compounds

October 19, 2016
Nitrogen-15 isotope can trigger asymmetric autocatalytic reactions toward chiral organic compounds
Credit: Wiley

The preparation of chiral compounds as intermediates in drug synthesis is one of the most important targets in synthetic organic chemistry. Japanese scientists have now shown that the autocatalytic preparation of a chiral intermediate can be triggered by a compound bearing hidden chirality, which consisted of nothing more than the difference between the isotopes nitrogen-15 and nitrogen-14. The study is published in the journal Angewandte Chemie.

Nitrogen-15 is one of the two naturally occurring nitrogen —although with an abundancy of only 0.37% compared to that of 99.63% for nitrogen-14. However, nitrogen-15 is frequently employed as a tracer isotope in biology, and it is a source of the radioisotope carbon-15 that is used in nuclear medicine imaging applications. A team of scientists led by Kenso Soai at Tokyo University of Science, Japan, have found a rather different application: as an initiator for the asymmetric autocatalytic reaction to prepare a chiral organic intermediate, that is, a compound distinguishable from its mirror-image.

Autocatalytic reactions are attractive in synthesis because once a product is formed it serves as a catalyst for the propagation of the reaction, making the use of external catalysts obsolete. This is especially attractive for asymmetric catalysis which often employs expensive and sophisticated compounds as catalysts. In asymmetric autocatalysis, a chiral trigger initiates the reaction. Soai and his team were particularly interested in a nitrogen-group-containing trigger molecule that relies on the smallest chiral induction possible: the difference of atomic mass between nitrogen-14 and nitrogen-15 is only 7%.

The difference is so small that the scientists could not detect it by conventional chiral analysis. But its effect could be shown as it induced asymmetry in the reaction of a pyrimidine moiety, which is a common building block in many biological molecules, and an alkylation reagent. The resulting pyrimidine alcohol was clearly chiral with one mirror-image dominating the other. "This result is the first example of enantioselective induction by using only the nitrogen isotope 14N/15N difference," the scientists reported. And it is a remarkable example of the effects that hidden chirality can have in synthesis.

Explore further: Artificial enzyme for asymmetric synthesis using a synthetic chiral polymer

More information: Arimasa Matsumoto et al. Asymmetric Induction by a Nitrogen 14N/15N Isotopomer in Conjunction with Asymmetric Autocatalysis, Angewandte Chemie International Edition (2016). DOI: 10.1002/anie.201608955

Related Stories

Radical route for the synthesis of chiral molecules

April 14, 2016

The research group of Prof. Paolo Melchiorre at ICIQ has developed a new methodology for the selective formation of chiral molecules. The work, that has been published in Nature, combines two strategies which require very ...

High-yield selective synthesis of specific molecules

July 6, 2012

Organic chemists seek synthesis reactions that produce high yields of very pure products. European researchers have developed novel synthetic reactions for a class of compounds particularly relevant to potential drug therapies.

Recommended for you

New X-ray spectroscopy explores hydrogen-generating catalyst

November 22, 2017

Using a newly developed technique, researchers from Japan, Germany and the U.S. have identified a key step in production of hydrogen gas by a bacterial enzyme. Understanding these reactions could be important in developing ...

0 comments

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.