Nobel Prize for simple but brilliant discovery of asymmetric organocatalysis

An efficient, “precise, cheap, fast and environmentally friendly” way to develop new molecules using a simple yet novel concept of catalysis — asymmetric organocatalysis — has won this year’s Nobel Prize for chemistry.

An efficient, “precise, cheap, fast and environmentally friendly” way to develop new molecules using a simple yet novel concept of catalysis — asymmetric organocatalysis — has won this year’s Nobel Prize for chemistry. The Prize has been awarded to German scientist Benjamin List of the Max Planck Institute and Scotland-born scientist David W.C. MacMillan of Princeton University who independently developed the new way of catalysis in 2000.

The duo developed “a truly elegant tool for making molecules — simpler than one could ever imagine”. Since then, the process developed by the two laureates has led to a “gold rush” in the catalysis field. The multitudes of new organocatalysts developed in the last two decades has helped drive a variety of chemical reactions, which in turn has accelerated pharmaceutical research to construct new drugs.

The asymmetric organocatalysts allowed researchers to efficiently produce new molecules with complete certainty of the 3-D orientation or handedness. Molecules naturally present and those synthesised can exist in two forms — right-handed and left-handed. The properties of the molecules very often vary depending on its handedness.

In late 1950 and early 1960s, thalidomide was widely used for the treatment of nausea in pregnant women. But in the short period that the drug was available, it caused severe birth defects in thousands of children. It later became clear that the left-handed molecules were beneficial as a drug, while the right-handed ones were highly toxic causing birth defects. But asymmetric organocatalysts allowed scientists to produce molecules of desired mirror image form.

While using other catalysts that require isolation and purification of each intermediate product, thus leading to loss of substance at every stage, the use of asymmetric organocatalysts allows several steps in molecule production to continue without interruption thus minimising waste.

In 2001, the three scientists who first developed asymmetric catalysts won the Nobel Prize in Chemistry. But such catalysts often use heavy metals, which make them expensive and also harmful to the environment. There are other challenges in using some of these metal catalysts — the high sensitivity to oxygen and water. This meant that industrial use of these catalysts made the process expensive.

Many enzyme catalysts too are asymmetric and are not sensitive to oxygen and water but these catalysts are very often much larger than the actual target medicine and can take a longer time to do their job. Instead of using enzymes which normally contain hundreds of amino acids, the two laureates developed a carbon-based catalyst made from a single, circular amino acid. Since these catalysts are asymmetric, only molecules of a single handedness are produced.

If Dr. List used a single amino acid proline to perform a certain bond-forming chemical reaction, Dr. MacMillan demonstrated that many modified amino acids could asymmetrically produce another bond-forming reaction. The circular-shaped amino acid used by both laureates ensured that only one mirror image of the molecule could be produced.

This year’s Prize underlines the often-ignored message — great discoveries can come even from simple ideas which are often overlooked.

Published in The Hindu on October 9, 2021