Oct 12, 2009 -

A pioneering new biomimetic path to synthesize the antifungal natural compound (+)-davanone has been discovered by David A. Vosburg, assistant professor of chemistry, and his team of students. Their strategy dramatically reduces the steps from 20 to seven and is the only synthesis of (+)-davanone known to have been performed solely by undergraduate students.

First discovered in 1968 from an Indian sage plant, davanone has useful antifungal and antispasmodic properties. “(+)-Davanone is the most prominent compound in a family of molecules that we call ‘davenoids,’” explained Vosburg who served as principal investigator. “Many are present in only a small amounts naturally. Our goal was to synthesize (+)-davanone in a short enough way to easily adapt the steps to make larger quantities of these related compounds and explore their properties.”

In May 2009, Vosburg and recent graduates Karen (Brown) Morrison ’08, Paul Dossa ’06, Jonathan Litz ’09 and Kathryn Scherpelz (Pomona ’09), published their findings, “A concise, biomimetic total synthesis of (+)-davanone,” in the Journal Organic Letters. Each of the three stereoselective reactions uses a catalyst to minimize waste. Superfluous protecting steps are eliminated, permitting an atom- and redox-economical synthesis.

The paper garnered significant attention as the fifth-most-accessed paper in the journal from April to June 2009. The HMC team’s findings were also excerpted in the article “Economies of synthesis” by Timothy Newhouse, Phil S. Baran and Reinhard W. Hoffmann in Chemical Society Reviews.

“Our method is superior in the number of steps, protecting groups used, and redox manipulations – less is better in each case,” noted Vosburg. “Our research therefore reflects step, atom and redox economy for a more sustainable chemical route.”

Of the 32 accomplishments highlighted in the Reviews article, HMC’s research is the only one to originate from a lab without graduate and postdoctoral students. “Probably very few, if any, of the other syntheses had even a single step performed by an undergrad; in our case it was all seven steps,” he said.

Vosburg compares synthesizing the (+)-davanone molecule to that of building a house. “There are a number of ways to build a house. Do you pour the foundation and put up the framing first or build it stone by stone? With (+)-davanone, some of it is trial and error, and some of it lies in strategic planning and knowing where to pick the right starting point,” he said.

Vosburg and his current research student Eric Nacsa ’10 are working to further shorten the synthesis from seven steps to four so it will be even more cost-effective. Additionally, they are collaborating with Katherine Maloney, assistant professor of chemistry, to research the effects davanoids have on suppressing fungal growth.