This year’s Nobel Prize for Chemistry is for an efficient, “precise, cheap, fast and environmentally friendly” way to develop new molecules using a simple yet novel concept of catalysis — asymmetric organocatalysis. It was 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. They came up with “a truly elegant tool for making molecules — simpler than one could ever imagine”. Since then, the process they evolved has led to a “gold rush” in the catalysis field. The multitudes of new organocatalysts developed have helped drive a variety of chemical reactions, in turn accelerating pharmaceutical drug research. The asymmetric organocatalysts have 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, and their properties very often vary depending on their handedness. In the 1950-60s, thalidomide was widely used to treat nausea in pregnant women, but caused severe birth defects. It became clear that the right-handed molecule was highly toxic. But asymmetric organocatalysts allowed the production of molecules of the desired mirror image form. While using other catalysts that require isolation and purification of each intermediate product — leading to loss of substance at every stage — asymmetric organocatalysts allow several steps in molecule production to continue without interruption, 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, making them expensive and environmentally harmful. There were other challenges too — a high sensitivity to oxygen and water. This meant that industrial use made the process expensive. Many enzyme catalysts too are asymmetric and are not sensitive to oxygen and water. But they 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, this year’s 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 Benjamin List used a single amino acid proline to perform a certain bond-forming chemical reaction, W.C. MacMillan demonstrated that many modified amino acids could asymmetrically produce another bond-forming reaction. The circular-shaped amino acid the laureates used 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.