Pitt Professor Finds Breaking the Rules Leads to Faster Chemical Synthesis New Method Could Speed Up Discovery of New Drugs

April 5, 2002

PITTSBURGH—Sometimes, thinking "outside the box" means breaking the rules, and University of Pittsburgh researcher Dennis Curran found that sidestepping one organic chemistry commandment meant finding a faster and more efficient way of creating new chemical compounds and, potentially, new drugs. Curran presented his radical chemistry methods in a lecture, Fluorous Mixture Synthesis Approaches to Natural Product Libraries, April 8 at the American Chemical Society's 223rd National Meeting in Orlando, Fla.

Curran, Pitt Distinguished Service Professor and Bayer Professor of Chemistry, was looking for a way to speed up the process of synthesizing complex molecules when he decided to challenge an old chemical adage: "Never mix pure organic compounds."

"The synthesis of complex molecules like natural products is painstaking and difficult and has always been done one at a time," said Curran. "In other words, if you want to create two, or four, or eight compounds, you have to perform two, or four, or eight painstaking syntheses."

Therefore, Curran and his research team began working on developing a new method to make complex molecules by working with mixtures.

The problem with mixing pure organic compounds is that it is extremely difficult to completely separate the ingredients after they have been mixed.

"The adage recognizes that if you mix compounds, you are asking for trouble when you need to separate and identify them," says Curran. "Our new process was a flagrant violation of that adage.

"We solved the separation and identification problem by introducing fluorous—highly fluorinated—tags. These tags allow us to reap the efficiency of mixture synthesis, making more compounds each time, yet we are still able to separate and identify the mixture components on demand," Curran says.

The process involves mixing two or more compounds at the beginning of the operation, then performing only one synthesis. At the end, the researchers demix, or separate, the products.

"So, we get more than one product from one synthesis, and the final products are individual and pure, as if they were made by separate syntheses," says Curran.

Curran's methods work especially well for synthesizing models of active natural products or other compounds to find the best drug candidate.

"Our new mixture methods should help to discover drugs more quickly," Curran says. "Perhaps even more important, they could lead to better drugs, since more compounds will be tested prior to selecting a drug candidate."

Curran and his colleagues have started a Pittsburgh-based company, Fluorous Technologies, Inc., to commercialize this technique and other fluorous discoveries.

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For more information:

http://radical.chem.pitt.edu/index.html

www.fluorous.com)