Award for asymmetric organocatalysis

This year’s Nobel Prize in Chemistry goes to two researchers who have independently discovered a group of completely new tools for customizing organic molecules. The identified catalysts also allow the targeted production of only one of the two variants of asymmetric molecules. Benjamin List from the Max Planck Institute for Coal Research in Mülheim found that individual amino acids such as proline were suitable catalysts for the production of such molecules. David MacMillan of Princeton University has identified further catalysts based on so-called iminium ions. Since then, the asymmetric organocatalysis developed by both researchers has opened up completely new possibilities for the production of customized organic molecules for use in chemistry, drug production and other fields.

Without catalysis, many chemical reactions would not take place and much of our own metabolism would not be possible. In order to break chemical bonds and create new ones, it is often necessary to overcome the energy barrier. The catalyst does this by temporarily participating in the reaction, for example by transferring electrons from one molecule to another. Before the two prize winners published their groundbreaking discoveries in 2000, only two types of such catalysts were known. In nature, as well as in the human body, enzymes serve as assistants in catalytic reactions. Entire series of such proteins are often linked in series to sustain complex biochemical reactions. However, the use of these enzymes for catalysis in the laboratory is complex and not always possible.

The second type of catalyst are inorganic metal compounds, such as those used in automotive exhaust gas treatment systems. However, they are usually not very environmentally friendly, and many of them only work effectively in the absence of oxygen and in a dry environment. Moreover, these inorganic catalysts usually produce mixtures of molecules, so-called racemates: for chiral molecules that are asymmetric in shape and exist in two configurations or “handedness”, these catalysts usually produce both forms in almost equal proportions. The problem though: especially in biochemistry and medicine, chirality plays a decisive role in the properties, function and behavior of a molecule. One variant may be an effective drug while the other is ineffective. This is where the work of the two award winners begins.

List: Amino acid as a catalyst

Benjamin Lists began his research with enzymes – complex proteins made up of hundreds of amino acids. He asked himself if the sum of all amino acids and their configuration are always necessary for the catalytic function of an enzyme: Could it be that only one or a few amino acids are sufficient for certain catalytic reactions? To find the answer, List experimented with the amino acid proline, which was known to be catalytically active in some chemical reactions. In his experiments, the researcher checked whether proline could catalyze the so-called aldol reaction. In this reaction, acetone and aromatic aldehydes react with each other and form new carbon-carbon bonds.

It worked: As List learned, the interaction of the nitrogen atom contained in proline with the proton of the reaction partner creates an intermediate product that stabilizes and supports the formation of a new compound. And not only that: unlike metal catalysts, one of the two asymmetric molecular forms was formed preferentially. The letter published its results in February 200 and described the concept as an entirely new form of asymmetric catalysis with organic molecules.

MacMillan: Wanted Iminium Ion

Around the same time, David MacMillan was working on a very similar catalytic principle at the University of California, Berkeley. He was looking for simple organic molecules that could form a specific ion, the so-called iminium ion. In this charged molecular form, the nitrogen atom is bound to the hydrocarbon structure such that it can accept an electron. Thanks to this, it can serve as a catalyst in chemical reactions. After experimenting with various molecules, MacMillan found the configuration that successfully and reliably formed the imine ion he wanted. Using the example of the Diels-Alder reaction in which cyclic hydrocarbon compounds are formed, the researcher not only showed that his organic catalysts work, but also preferentially produce one of the two asymmetric molecular forms. His results were also published in 2000, and MacMillan coined the term organocatalysis for them.

“The concept of catalysis is as simple as it is genius,” says Johan Åqvist, chairman of the Nobel Prize Committee in Chemistry. The work of List and MacMillan created the starting point for an entirely new field of catalysis, and thus opened up new possibilities for the easy production of asymmetric molecules in the desired configuration. In addition to raw materials for the production of pharmaceuticals and chemicals, this includes, for example, new materials for organic solar cells. Since organic catalysts are also non-toxic and environmentally friendly, unlike many metal catalysts, they also help make chemistry a bit greener.

Source: Nobelprize.org

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