Roger Adams Award in Organic Chemistry

William Schulz

Sponsored by Organic Reactions Inc. and Organic Syntheses Inc.

Samuel J. Danishefsky has been called one of the most inventive synthetic chemists of the day. In fact, "the central quest of his four-decade-long career has been that of enlarging the power of organic synthesis," comments Julius Rebek, director of Skaggs Institute for Chemical Biology and a professor of chemistry at Scripps Research Institute.

Danishefsky, 71, is a professor of chemistry at Columbia University and is the Eugene Kettering Chair and director of the Laboratory for Bioorganic Chemistry at Memorial Sloan-Kettering Cancer Center in New York City. He is an internationally recognized leader in chemistry, specializing in the synthesis of biologically active organic compounds.

Highlights of Danishefsky's career include original insights into the chemical potential of vinylpyridines, which led to total syntheses of steroids. The use of highly electrophilic allenes was pivotal in an early synthesis of camptothecin. His total synthesis of mitomycin led to the first characterization of the highly labile leucomitosenes and the demonstration of chemical models for in vivo drug activation.

In the mid-1970s, Danishefsky commenced a lifelong investigation of synergistic dienes in the Diels-Alder reaction. These dienes were derived from extended silyl enol ether motifs and led to the total syntheses of a broad range of natural products. Danishefsky's dienes are used worldwide in chemical synthesis.

In the mid-1980s, Danishefsky described the Lewis-acid-catalyzed diene aldehyde cycloaddition reaction leading to dihydropyrones. This chemistry was organized to provide a general strategy for the stereoselective total synthesis of polypropionate-derived natural products, culminating in a synthesis of zincophorin.

Natural product total synthesis has been a recurring theme in Danishefsky's work. Each synthesis is dedicated to studying one or more key issues of reaction design or reaction feasibility. Representative triumphs of the past decade include FK506, rapamycin, 5-N-acetylardeemin, gypsetin, paclitaxel (Taxol), dysidiolide, eleutherobin, himastatin, tricycloillicinone, halichlorine, rishirilide B, radicicol, pinnaic acids, heliquinomycinone, gelsemine, TMC-95, merrilactone, guanacastepene, cycloproparadicicol, migrastatin, lactonamycinone, and aigialomycin.

Using a strategy that he termed glycal assembly, Danishefsky has developed a number of fully synthetic tumor-associated, carbohydrate, antigen-based vaccines, consisting of homogeneous oligosaccharide antigens that simulate cell-surface oligosaccharides on tumor cells. These are by far the most complex fully synthetic homogeneous vaccines ever brought forward to the clinic.

Finally, in 2003, Danishefsky described major advances in the total synthesis of glycopolypeptides containing complex-carbohydrate, high-mannose motifs. These are the most complex glycosylated peptides of defined structure ever produced in a laboratory.

Danishefsky earned a bachelor's degree in chemistry at Yeshiva University in 1956 and a Ph.D. degree in chemistry from Harvard University in 1962. After a stint as a Columbia University/NIH postdoctoral fellow with Gilbert Stork, Danishefsky became an assistant professor at the University of Pittsburgh in 1964. In 1979, he became a professor at Yale University, where he stayed until his current joint appointment at Columbia University and the Sloan-Kettering Institute for Cancer Research in 1991.

Danishefsky has won numerous scientific awards and is the author of more than 620 publications.

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