Issue Date: January 29, 2007
ACS Award for Creative Invention
Sponsored by Corporation Associates
"Bruce Ganem recognized a fundamental gap in synthetic methodology and then invented a new reaction to plug it," says Dennis Curran, a chemistry professor at the University of Pittsburgh. "The story is a beautiful example of the synergy between academic and industrial research."
The story concludes with a commercially viable and environmentally benign way to mass-produce paclitaxel (Taxol), one of the most successful anticancer agents developed in the past 50 years. Paclitaxel is a natural product found in rare Pacific yew trees and had been previously synthesized only from scarce materials (C&EN, June 20, 2005, page 120). But by using a unique reaction that Ganem discovered, it can now be made from more abundant compounds found in common yew trees.
Ganem joined the faculty at Cornell University in 1974. He is currently Franz & Elisabeth Roessler Professor in the department of chemistry and chemical biology and J. Thomas Clark Professor of Entrepreneurship. He has published and patented numerous basic and applied advances in synthetic organic chemistry.
His path to a new paclitaxel synthesis began in the mid-1990s, when his lab was studying ways to deoxygenate organic compounds. With the help of two "terrifically important" postdocs, Alexander Godfrey (now at Eli Lilly & Co.) and David Schedler (now a chemistry faculty member at Birmingham-Southern College in Alabama), Ganem's lab made a key finding.
"We serendipitously discovered that we could deoxygenate amide bonds, and the reaction product was the corresponding imine," Ganem says. The researchers employed organozirconium hydrides, one of which is known as Schwartz's reagent, for that reduction.
The papers were a "breakthrough," Curran says. "There were no previous methods to reduce amides to imines, and no others have emerged since."
"Reducing amides to imines, at room temperature, in one step, in reasonable yield, and by a procedure requiring no more complex workup than a filtration, represents not only a considerable advance in synthetic methodology, it is also of great practical significance," says Gilbert Stork, a chemistry professor at Columbia University.
A process based on Ganem's findings was subsequently patented for preparing paclitaxel from primary taxanes by modifying their amide side chain to a primary amine via an imine and finishing off with a simple benzoylation. Ganem credits a company called Natural Pharmaceuticals for discovering that ordinary yews contain a bounty of primary taxanes, engineering a commercial synthesis of paclitaxel, and addressing environmental issues by caring for millions of yew trees on their native upper Michigan peninsula.
Ganem was born and raised in Boston. He earned a B.A. in chemistry from Harvard University in 1969 and a Ph.D. in organic chemistry from Columbia University in 1972. He was a postdoctoral fellow at Stanford University.
Among his awards for scholarship and teaching, Ganem was named an Arthur C. Cope Scholar Award winner in 1996 and received the National Catalyst Award for excellence in science teaching in 1999. He has acted as a preceptor for ACS Project Seed, a program for disadvantaged high school students; sat on many editorial boards and scientific advisory boards; and launched several start-up companies.
The award address will be presented before the Division of Organic Chemistry.
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