Sharpless, K. Barry

K. Barry Sharpless, (born April 28, 1941, Philadelphia, Pennsylvania, U.S.), American scientist who was cowinner of the Nobel Prize for Chemistry in 2001 and 2022. He shared the 2001 prize with William S. Knowles and Noyori Ryōji for developing the first chiral catalysts. With Morten P. Meldal and Carolyn R. Bertozzi he was awarded the 2022 prize for contributions to click chemistry and bioorthogonal chemistry. Sharpless was just the fifth person to receive two Nobel Prizes.

Sharpless received a Ph.D. from Stanford University in 1968. After postdoctoral work, he joined the Massachusetts Institute of Technology (MIT) in 1970. In 1990 he became W.M. Keck Professor of Chemistry at the Scripps Research Institute in La Jolla, California.

Many molecules are chiral—they exist in two structural forms (enantiomers) that are nonsuperimposable mirror images. Likewise, the receptors, enzymes, and other cellular components made from these molecules are chiral and tend to interact selectively with only one or two enantiomers of a given substance. For many drugs, however, conventional laboratory synthesis results in a mixture of enantiomers. One form usually has the desired effect while the other form may be inactive or cause undesirable side effects, such as occurred with the drug thalidomide. This problem led scientists to pursue chiral catalysts, which drive chemical reactions toward just one of two possible outcomes.

Sharpless’s research focused on chiral catalysts for oxidations, a broad family of chemical reactions. Atoms, ions, or molecules that undergo oxidation in reactions lose electrons and, in so doing, increase their functionality, or capacity to form chemical bonds. In 1980, working at MIT, Sharpless carried out key experiments that led to a practical method based on catalytic asymmetrical oxidation for producing epoxide compounds, used in the synthesis of heart medicines such as beta blockers and other products.

In the 1990s Sharpless coined the term click chemistry to describe a process whereby simple, quick chemical reactions—much like snapping two ends of a seat belt together—could be used to make new chemical molecules. By using molecules with carbon frames as a starting point and by choosing simple reactions with a strong drive to bind the molecules together, chemists could produce new chemical entities while also avoiding the generation of unwanted by-products and a loss of materials. Shortly after developing the concept of click chemistry, independently of Meldal, but about the same time, Sharpless discovered what became the principle click reaction, copper-catalyzed azide-alkyne cycloaddition (CuACC). Sharpless’s and Meldal’s discoveries opened the way for chemists to generate numerous different compounds with a wide range of potential applications, particularly in the areas of pharmaceutical development, polymer chemistry, and materials science.