Organic chemist Robert A. Holton dies at 81

Robert A. Holton, a retired Florida State University professor, died at his home in Tallahassee, Florida, on May 21 at the age of 81.

Holton is best known for his work on the anticancer drug Taxol (paclitaxel). The molecule was first discovered in scant quantities in the bark of the Pacific yew tree, Taxus brevifolia, during a study initiated by the National Cancer Institute. In 1963, scientists found that extracts from the tree had outstanding potential as a drug and eventually identified the key chemical component as paclitaxel. But commercializing the compound didn’t seem feasible. Extracting 0.5 g of paclitaxel required cutting down a 12 m tree, which may have taken 200 years to reach that height.

A related compound, 10-deacetylbaccatin III, which contains paclitaxel’s complex ring system, could be extracted from the needles and twigs of the English yew shrub, a common garden plant. In 1989, Holton developed a 4-step semisynthesis of paclitaxel, which weds 10-deacetylbaccatin III’s skeleton with paclitaxel’s side chain. By using a readily available renewable resource, Holton’s chemistry transformed paclitaxel into a commercially viable product. Drugmaker Bristol-Myers Squibb licensed the route and brought Taxol to market in 1993.

David Kingston, an emeritus professor at Virginia Tech who worked on compounds related to paclitaxel, says in an email that the route “provided an elegant solution to the ‘Taxol supply crisis’ of the early 1990s and incidentally made Bob a wealthy man.”

Holton’s group also completed the first total synthesis of paclitaxel from simple starting materials—work the chemists published in 1994. Although that route was never used to make the drug, many chemists from top synthesis labs were racing to be the first to make the molecule.

Holton was born in Fayetteville, North Carolina. He earned his bachelor’s degree in chemistry from the University of North Carolina at Chapel Hill and his doctorate from Florida State University. After postdoctoral work at Stanford University, Holton held faculty positions at Purdue University and Virginia Tech. In 1986, he joined the faculty at his alma mater Florida State University, where he spent the remainder of his career teaching and conducting research as a Distinguished Research Professor. He retired in 2023.

When the National Academy of Inventors named Holton a fellow in 2018, he said, “I have always been drawn to difficult problems, and synthesizing Taxol was a big one. Seeing the drug’s success in treating so many patients has been an incredibly gratifying experience.”