Awards Database

Cottrell Scholar Awards - 2009

Scott Snyder

Columbia University

Synthesizing Molecules of Red Wine

An ingredient in red wine and grape skins called resveratrol has been offered for years to help explain the French Paradox - despite high intake of fats, relatively few heart attacks. That ingredient is used by grapes and more than 70 other plants throughout the world to fashion hundreds of other molecules that appear to have important health benefits. With some original thinking, Scott Snyder, a synthetic organic chemist at Columbia University, is seeking to find ways to mirror what plants do naturally - manufacture those complex molecules called oligomers. He hopes to better understand their behavior and the uses of this ancient ingredient in a wide range of diseases and other modern applications. Resveratrol and the molecules made from it, it turns out, are made by plants to defend against pathogens, primarily fungal infections. In mice, however, they appear to extend the aging process and aid against tumors, and in humans there are high hopes that they can do everything they do in mice and even help ward off heart trouble. Snyder's work may expand our knowledge of how they work and may defend our bodies against other diseases like H.I.V. The molecules he and his students are creating may one day help protect against bird flu or serve as insecticides. "Nature makes these compounds not to cure human disease but to allow the producing organism to survive," Snyder says. "They take resveratrol and use it like a Lego set, putting two or three or even 10 together to make dozens of natural products all at once. Our goal was to figure out how we could create these structures one at a time so we could study them further." That's the really tricky part, Snyder says, the problem of controlled synthesis. Learning how won't come quickly, but Snyder's lab is well on the way. If you look at the 500 or so chemicals in grapes that add up to red wine and account for its subtle variations in taste and color, there's only one polyphenol that is unique to red wine that is not found in appreciable quantities in white wine and grape juice, and that's resveratrol. That, says Snyder, was one anomaly worth studying. Here's another. Of the 700 complex molecules made from resveratrol that have been isolated from plants, nearly all result from predictable patterns of chemical reactivity; 10 or so of these structures, however, don't fit chemists' expectations and had been regarded largely as synthetic anomalies, something that went off track. "They were the black sheep members of the family," Snyder says. "But they pointed us to a different way to begin this synthesis." After six months of false starts in his lab and building on 30 years of failed attempts by other chemists to solve the same problem, Snyder realized that the key clues resided in those anomalies. To get to the synthesis of compounds made from resveratrol, he knew he had to create an original molecule to serve as a new starting point for a vital series of reactions. "We shifted our approach and started looking at the oddballs, playing with different ideas for what they were indicating that starting point could be," he says. As a result, they ended up revealing the structure of a new building block that could reach the desired outcome, the controlled synthesis of compounds built from resveratrol. Snyder and his team have now applied the same lesson to achieve the synthesis of other important bioactive molecules from nature as well. "The moral of the story is, don't dismiss an anomaly. Find a way to use it," says Snyder, who has been doing science since childhood. In Buffalo, N.Y., his father was a biochemist who made Scott feel at home in the lab; his mother was a mathematician. In high school, he was one of 20 finalists selected in 1995 to compete as representative for the United States in the International Chemistry Olympiad and was a semi-finalist in the Westinghouse Science Talent Search. He was then a top chemistry major at Williams College, received a Ph.D. at Scripps Research Institute, and was a postdoctoral fellow at Harvard in the laboratory of a Nobel Laureate. Millennia ago, plants made the compounds like resveratrol because of evolutionary pressure to survive. Now, on the fifth floor of legendary Havemeyer Hall where Nobel Prize-winning ideas in chemistry are almost old hat, Snyder's lab seeks to harness those eons of evolution and adapt them in ways that may point to groundbreaking applications.

Scott Snyder's Teaching Plans

Snyder says he became a scientist as a result of childhood experiences that he would like to replicate as part of his Cottrell grant. In high school in Buffalo, N.Y., he spent three summers doing research in a lab with one of his father's colleagues in the Department of Biology at SUNY Buffalo. Now he plans two programs to excite high-school students about the research environment. Snyder will recruit students from a high school in Dobbs Ferry, N.Y., where he lives, to take part in summer programs at Columbia, where they will be matched with chemistry colleagues on the faculty. "There's never been a high-school student doing forefront research at Columbia," Snyder said. "We are doing something new." In addition, he will bring one teacher and two students from a nearby school in New York City into his own lab for up to eight weeks of summer research experience. "We'll offer them some training in modern science," Snyder said, "and let them develop experiments in organic chemistry that they can continue through the year. The program will have some longevity, and thus we hope it will inspire dozens of more students." Their task: synthesize resveratrol, the molecule that started it all for the Snyder group.

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