Utah Chemists Develop New Catalytic Reaction; Method May Prove Useful For Industrial Production Of Medicines

"We've shown a new way to produce alcohol building blocks for drugs," says Matt Sigman, an assistant professor of chemistry. "We're looking to see how much we can improve this method before it might turn into some sort of industrial process."

Sigman, an organic chemist, conducted the research with chemistry doctoral student David R. Jensen and undergraduate Jacob S. Pugsley. Their findings were published Aug. 1 in the Journal of the American Chemical Society - one week before the same journal published a report of a similar accomplishment by chemists at the California Institute of Technology. Both studies also were highlighted in Chemical & Engineering News, an industry publication.

A catalyst is a substance that triggers or speeds a chemical reaction without being consumed in the process. Sigman said the new method is among the first in which oxygen has been used by a catalyst in a reaction capable of making medicinal compounds.

In the study, Sigman and colleagues tested 10 different catalysts that were nitrogen-based compounds containing the metallic element palladium. They discovered one such catalyst - named palladium II sparteine - was able to use molecules of oxygen to help change or "oxidize" certain forms of alcohol to substances called ketones.

Sigman said the new reaction could be useful in producing medicines because the active ingredients of many drugs contain alcohols. Those alcohols have a property called "chirality," which means a certain type of alcohol molecule has both a left-handed form and a right-handed form. Even though both forms contain the same atoms, one form may be active and the other may be inactive. So chemists often separate the inactive and active forms of any alcohol molecule used to make a medicine.

He said examples of medications that must be made from only the active form of a "two-handed" or chiral molecule include the painkiller naproxen, the breast cancer drug taxol, albuterol for asthma, cholesterol-lowering Lipitor and the antiviral AIDS drug indinavir.

Left- and right-handed forms of any specific type of alcohol now are separated by other chemical reactions, including using enzymes or other catalysts. But any single enzyme is not effective on different kinds of alcohols. By comparison, the new reaction has worked on most types of alcohol tried so far, Sigman said.

Sigman said the catalytic reaction that uses oxygen is better than other catalytic reactions because oxygen is inexpensive and readily available, and because the reaction results in nontoxic byproducts, including water.

The Utah researchers now are trying to improve the method so it separates different forms of alcohol more efficiently without destroying any of the desired form. Sigman also wants to improve the catalytic reaction so it can be done with air instead of pure oxygen, and at room temperature instead of 70 degrees Celsius (158 degrees Fahrenheit) - the temperature used in the recently published study.