Ernest Guenther Award In The Chemistry Of Natural Products

Sponsored by Givaudan

In 2001, Dennis P. Curran and coworkers at the University of Pittsburgh introduced an organic synthesis technique called fluorous mixture synthesis that the group has leveraged into a powerful approach for making natural products and other complex organic compounds enantioselectively.Curran is receiving the Ernest Guenther Award this year for “creative syntheses of natural products and natural product stereoisomer libraries” based on the fluorous approach and other techniques his group has created and refined.

In fluorous mixture synthesis, fluorine-containing tags of different kinds are added to different starting materials, the starting materials are combined and reacted together to produce product mixtures, and the tags are then used to isolate and purify specific desired products from the mixtures. The primary advantages of the technique over conventional nonfluorous syntheses are efficiency and convenience—it saves steps by carrying out reactions in parallel, rather than one by one, and yet still generates pure products conveniently, without a lot of difficult separations fuss.

Some complex fluorous syntheses ­carried out by Curran’s groups have yielded up to 32 pure final products. “No one has done anything even remotely comparable to what Curran has achieved with fluorous mixture synthesis,” comments chemistry professor Peter Wipf, a colleague at Pitt.

“Curran is also a brilliant strategist,” Wipf notes. This quality is exemplified by the Curran group’s development and use of a technique called tandem radical reactions. The approach, in which short series of radical reactions are used to create natural products and natural-product-like compounds, obviates the need to use protecting-group chemistry and is spare in numbers of steps needed.

Curran and coworkers demonstrated the power of the technique by using it to make substantial amounts of an enantiomerically pure version of a cancer drug called AR-67 for clinical trials. They also used radical reaction chemistry to carry out a highly efficient synthesis of the anticancer agent camptothecin and more than 100 camptothecin derivatives, as well as to synthesize the complex five-fused-ring natural product meloscine.

“Curran’s productivity is superior,” Wipf says. “In well over 100 papers, he describes total syntheses of scores of natural products and hundreds of their analogs and isomers. Each offers a combination of new synthetic chemistry, new tagging or separation methods, structural assignments, bioassays, and more. Many of Curran’s other papers describe creative synthetic methodology advances that are directly applicable to natural products.”

Chemistry professor Samuel J. Danishefsky of Memorial Sloan-Kettering Cancer Center and Columbia University adds that Curran “has had a long and distinguished career spanning the gamut of natural products chemistry, is a real statesman in the field, and has fashioned a wonderful continuity of excellence at Pitt.”

Curran, 60, earned a bachelor’s degree in chemistry from Boston College in 1975 and a Ph.D. from the University of Rochester in 1979.

After serving as a postdoc in chemistry professor Barry M. Trost’s group at the University of Wisconsin, Curran joined the Pitt faculty in 1981. He is currently Distinguished Service Professor and Bayer Professor of Chemistry there.

Curran will present his award address before the Division of Organic Chemistry.