Nobel Laureates in Chemistry 2021

We were delighted to learn that the 2021 Nobel Prize in Chemistry has been awarded to two scientists of enormous stature: the German Benjamin List (Frankfurt, Germany, 1968) of the Max Planck Institute for Coal Research and the US-based Scotsman David MacMillan (Bellshill, UK, 1968) of Princeton University (USA).
The Royal Swedish Academy of Sciences based its decision on the fact that the two have (independently) developed a third type of catalysis: asymmetric organocatalysis, based on small organic molecules.

Historical background

For the layman, I propose a historical journey to understand what is going on.
It was 1955 in the Swiss city of Zurich when Professor Robert Burns Woodward of Harvard University first presented to the world the synthesis of strychnine, whose molecule has one of the most complex structures ever found. The aim was to create the strychnine molecule in the laboratory from smaller chemical components.

In fact, Robert B. Woodward and Robert Robinson had just established independently in their respective laboratories the heterocyclic structure of strychnine. The event is so extraordinary that it is one of the most famous syntheses in the history of organic chemistry. The two scientists, Woodward and Robinson, won the Nobel Prize in Chemistry (we recommend the interesting article by Professor Antonio Soler Martínez of the University of Murcia, Síntesis total de la estricnina -Total synthesis of strychnine, in English-).

This milestone would not have been possible without the use of catalysts: substances that stimulate and accelerate chemical reactions without becoming part of the final product. The known catalysts were of two types, either metals or enzymes (organic molecules that accelerate the rate of reaction in chemical reactions). In the case of strychnine synthesis these were the available catalysts.

Nobel Laureates in Chemistry 2021. Benjamin List and David MacMillan

The genius of this year’s two laureates, List and MacMillan, is the systematic development of an idea that was not entirely new. In 2000, they independently introduced a third type of catalysis, which is based on small organic molecules(organocatalysis) and is highly effective in the case of the example in this article, in the synthesis of the complex molecule strychnine.

Note that in 1955 it took up to 29 different chemical reactions to decode its molecular structure and only 0.0009 per cent of the starting material formed strychnine, with the rest being wasted, whereas in 2011 researchers were able to use organocatalysis to synthesise strychnine in just 12 steps and the process was about 7,000 times more efficient.

It is a magnificent example of the enormous possibilities opened up by List and MacMillan’s organocatalysis.

Asymmetric catalysis

There is also a striking feature of these organic catalysts that led to their rapid expansion in the pharmaceutical industry.

The serious drawback of classical catalysts is well known: in the process of synthesising a certain molecule, another molecule can be created at the same time, which is the mirror image of the first one (as our right hand is to our left hand). This can be extremely serious, for example, in the production of pharmaceuticals, because the properties of the two molecules can be completely different.

Unfortunately, this is precisely what happened around 1960, when a mirror image of thalidomide caused severe foetal malformations.

Finding methods that produced only a certain molecule and not the specular one was not easy… until List and MacMillan developed asymmetric organocatalysis, which makes it possible to produce large volumes of asymmetric molecules relatively easily

On poisons and Agatha Christie

But let’s move on to the protagonist of our article, strychnine.

Outside the scientific world, our knowledge of strychnine is largely due to the magnificent pen of Agatha Christie. Already in her first detective novel of 1920, The Mysterious Affair at Styles the protagonist is the poison strychnine, which kills Mrs. Inglethorp.

The effect of strychnine poison is perfectly described by Agatha Christie in the morning scene in which Captain Hastings, Hercule Poirot‘s inseparable friend, witnesses the death of Mrs. Inglethorp: “One last seizure twisted her body so horribly that only her head and heels still touched the bed”.

The description of the poisoning, in terms of symptoms and the methodology used, was so faithfully recreated that the novel was reviewed in 1978 in the UK’s The Pharmaceutical Journal. The author of the article described The Mysterious Affair at Styles as “a novel that has the rare merit of being well written” and suggested that the author either had a good knowledge of pharmaceuticals or was assisted by experts. Years later (1992) other authors revisited the book in an academic article published in the Journal of Chemical Education and found the text to be appropriate for chemistry students.

Science and literature never cease to surprise us.

Author: Manuela Maza Ruiz.


Síntesis total de estricnina – Strychnine total synthesis –

Synthesis of Strychnine by Robert B. Woodward (1954)

Información sobre ”La síntesis total de la Estricnina” Dr. Antonio Soler Martínez. Catedrático de la Facultad de Ciencias (Universidad de Murcia)

Kathryn Harkup, “ A is for arsenic: the poisons of Agatha Christie”

Anales de la Real Academia de Medicina y Cirugía de Valladolid . EL VENENO EN LA NOVELÍSTICA DE AGATHA CHRISTIE (1890-1976). THE POISON IN THE AGATHA CHRISTIE`S NOVELS (1890-1976). Alfonso Velasco Martín1, Alfonso Velasco Sendra2 1 Académico de Número. 2 Doctor en Historia.

“Veneno de mujer”. José de Cora y Óscar Soriano. Ed. Edhasa. Barcelona. Febrero 2021. ISBN: 978-84-350-4801-9
ISBN 978-0-646-94370-1