American chemist who, with Noyori Ryōji and K. Barry Sharpless (Sharpless, K. Barry), won the Nobel Prize for Chemistry in 2001 for developing the first chiral catalysts.

Knowles earned a Ph.D. from Columbia University in 1942, after which he conducted research at the Monsanto Company in St. Louis, Missouri, until his retirement in 1986.

Many molecules (molecule) 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.

In 1968 Knowles produced the first chiral catalyst for an asymmetrical hydrogenation reaction. He was seeking an industrial synthesis for the drug -dopa, which later became a mainstay for treating Parkinson disease. Variations of the new catalyst found almost immediate application in producing very pure preparations of the desired l-dopa enantiomer.