Ernest Guenther Award in the Chemistry of Natural Products

Sponsored by Givaudan

"In recognition of contributions to the total synthesis of complex biologically active natural products and key analogs used to define their mode of action," this year's Ernest Guenther Award goes to chemistry professor Dale L. Boger of Scripps Research Institute. According to a colleague, "Boger has defined future directions for the field through his judicious choice of problems combined with the creativity of organic synthesis to address timely and important questions at the interface of chemistry and biology."

Boger, 53, was born in Hutchinson, Kan. He earned a B.Sc. with honors in chemistry and highest distinction from the University of Kansas in 1975 and a Ph.D. in organic chemistry at Harvard University in 1980, where he worked in chemistry professor and Nobel Laureate E. J. Corey's group. In the early 1980s, he served as assistant and then associate professor of medicinal chemistry at the University of Kansas. In 1985, he moved to Purdue University, where he was promoted to professor of chemistry and medicinal chemistry in 1987. In 1990, he became founding editor-in-chief of Bioorganic & Medicinal Chemistry Letters and continues to serve in that capacity. Since 1991, he has been the Richard & Alice Cramer Professor of Chemistry at Scripps.

Boger's research achievements span multiple areas: natural products total synthesis, synthetic methodology, studies of naturally occurring DNA-binding agents and glycopeptide antibiotics, combinatorial chemistry, and drug-target validation.

He and his coworkers have prepared over 80 natural products by total synthesis, including the vancomycin aglycon, bleomycin A2, camptothecin, ramoplanin aglycons, several duocarmycins, and yatakemycin. Many of these studies were first syntheses, established the relative and absolute stereochemistry of the compounds, were accomplished by developing novel synthetic methodologies, and/or led to the synthesis of structural analogs.

Synthetic methodologies Boger and coworkers have either developed or helped introduce include several types of hetero Diels-Alder reactions; a [4+2] transition state, anomeric effect-mediated endo diastereoselection; cyclopropenone ketal cycloaddition reactions, including a cycloaddition involving reversible -delocalized singlet carbene generation; Pd(o)-catalyzed amination of aryl bromides; synthetic applications of acyl radical generation from phenylselenoesters; and tandem Diels-Alder/1,3-dipolar cycloadditions of oxadiazoles. Boger's group also defined a concept of divergent synthesis that became a cornerstone of combinatorial chemistry and pioneered solution-phase combinatorial synthesis.

Boger and coworkers have explored chemical mechanisms of action, established binding and reaction selectivities, and synthesized analogs of a number of DNA-binding agents, including the duocarmycins, bleomycin A2, several bisintercalators, isochrysohermidin, and distamycin.

Boger's group has synthesized and characterized aglycons of a number of glycopeptide antibiotics, including vancomycin, teicoplanin, ristocetin, ramoplanin, and ramoplanose, and they recently reported reengineering the vancomycin core structure to improve its action against vancomycin-resistant bacteria. In combinatorial chemistry, Boger and coworkers pioneered multistep solution-phase combinatorial synthesis, helped develop liquid-liquid and liquid-solid extraction and polymer-scavenging techniques for purification of library compounds, and synthesized some of the earliest natural- product-like libraries.

"Dale Boger is one of the most imaginative people in organic synthesis," says chemistry professor Samuel J. Danishefsky of Memorial Sloan-Kettering Cancer Center and Columbia University, New York City. "His creativity is manifested not only in the way he solves problems but also in his recognition of important problems and in his ability to go beyond the syntheses themselves and extend their impact by asking and answering the right questions."

The award address will be presented before the Division of Organic Chemistry.—Stu Borman