Sharpless, K. Barry (1941-…), is an American chemist. He was a recipient of the 2001 and 2022 Nobel Prizes in chemistry. Each prize was awarded to Sharpless and two other chemists. Sharpless became the fifth person to receive two Nobel Prizes, and the second to receive two Nobel Prizes in chemistry.
In 2001, Sharpless was awarded a share of the chemistry prize for his creation of molecules that are widely used in the manufacture of drugs and other products. The other two recipients of that year’s prize were the American chemist William S. Knowles and the Japanese chemist Ryoji Noyori. Knowles and Noyori created molecules that function in much the same way as those developed by Sharpless. The three scientists worked separately. The molecules created by the prizewinners share three characteristics: (1) they are catalysts, (2) they are synthetic, and (3) they are chiral.
A catalyst is a substance that increases the speed of a chemical reaction without being consumed by the reaction. A chemical reaction converts one or more substances into one or more different substances. The starting substances are known as reactants, and the final substances are the products. Catalysts enable drug manufacturers to make large amounts of certain products quickly.
Synthetic molecules are created in a laboratory or a manufacturing facility. Many drugs are synthetic. They are duplicates or improved versions of drugs obtained from natural sources, such as plants, molds, bacteria, animals, or minerals.
Chiral molecules occur in pairs. Both molecules of a pair consist of the same kinds of atoms and the same number of each kind. However, the atoms are arranged in forms that mirror each other. As a result, the molecules differ from each other as your left hand differs from your right hand. Most drugs consist of chiral molecules. In some cases, only the left-handed form can provide the desired medical benefit. The right-handed form may provide no benefit, or it may even cause harm.
Knowles and Noyori worked on a kind of reaction, known as hydrogenation, that adds hydrogen atoms to a molecule. In 1968, Knowles created a catalyst that accomplished a “first” for a hydrogenation reaction. The catalyst helped convert a nonchiral reactant into a chiral product containing more of one chiral form than the other. Before Knowles’s work, no one knew how to synthesize chiral drugs without producing equal amounts of both forms. As a result, manufacturers made both forms, then separated them and discarded the right-handed molecules—half the product.
Beginning in the 1980’s, Noyori created catalysts that produced high percentages of the left-handed form of the product. He also created individual catalysts that worked with several kinds of molecules.
Sharpless worked on a different kind of reaction, called oxidation. In an oxidation reaction, a reactant loses one or more electrons. In 1980, Sharpless created a catalyst that accomplished for oxidation reactions what Knowles’s pioneering catalyst had accomplished for hydrogenation reactions. Methods developed by Sharpless to produce that catalyst and others now enable manufacturers to produce safer and more effective antibiotics, anti-inflammatory drugs, heart medicines, and agricultural chemicals.
Sharpless was awarded a share of the 2022 Nobel Prize in chemistry for his development of click chemistry, a new approach to assembling molecules. The other two recipients were the Danish chemist Morten Meldal and the American chemist Carolyn Bertozzi.
To create a new substance, chemists often use complex reactions to combine smaller “building block” molecules into a larger molecule. It may to be natural for the building blocks to bond easily, or they may assemble incorrectly. Chemists can take steps to make the building blocks assemble correctly, but the process may create complicated, inefficient reactions with unwanted byproducts.
Sharpless proposed click chemistry as a more efficient strategy for creating larger molecules. Click chemistry reactions can be simpler because they use connector molecules to link components together. Chemists compare the connector molecules to “buckles” that link the building blocks. The building blocks may not connect readily, but the buckles can “click” together quickly and easily.
Working independently, Sharpless and Meldal developed copper catalyzed azide-alkyne cycloaddition. This chemical reaction was one of the first chemical reactions in click chemistry. It is now used widely in the production of drugs and other products. Bertozzi developed click chemistry reactions that do not require copper, and therefore can be used harmlessly in living cells.
Karl Barry Sharpless was born in Philadelphia, Pennsylvania, on April 28, 1941. In 1968, he obtained a Ph.D. degree in chemistry at Stanford University in California. Sharpless worked as a postdoctoral researcher at Stanford in 1968, and then at Harvard University in Cambridge, Massachusetts, in 1969. In 1970, he joined the faculty at Massachusetts Institute of Technology (MIT) in Cambridge. Sharpless returned to Stanford in 1977. He rejoined the MIT faculty as a professor in 1980. In 1990, Sharpless was appointed the W. M. Keck Professor of Chemistry at the Scripps Research Institute in La Jolla, California. In 1996, he also became affiliated with the Skaggs Institute for Chemical Biology at Scripps.
