The next generation of single-enantiomer catalysts

Many molecules are enantiomers: they have mirror- image versions that may have identical parts but are just as different as your left hand is from your right. The value of a drug, however, could depend on whether it is a lefty or a righty, so researchers at the University of Pennsylvania are creating catalysts that will force drug molecules to choose sides.

Today, at the American Chemical Society 228th National Meeting, Penn chemist Marisa C. Kozlowski details the methods her lab is using to create the next generation of single-enantiomer catalysts.

"Enantiomers can pose a problem in pharmaceutical research, since the mirror-image of a particular molecule may be harmful or, at the least, useless," said Kozlowski, an associate professor in Penn Department of Chemistry. "Thalidomide is one famous example. The drug was created was as a mixture of both enantiomers, but researchers at the time did not know the left-handed version caused severe birth defects."

Not all effects of enantiomers are bad, of course. Spearmint takes its flavor from the right-handed version of a molecule called carvone, while its left-handed enantiomer creates the taste of caraway oil. Recently, however, the potential of harmful enantiomers has come to the attention of the Food and Drug Administration, which promotes the development of single-enantiomer drugs. (See the 1992 policy statement at the FDA Web site.) This has created a pressing need for pharmaceutical companies to develop single-enantiomer drugs.

Unfortunately, the chemistry of creating mixtures of enantiomers is much better known than that for creating batches of single-enantiomer drugs. It was only in 2001 that researchers were awarded a Nobel Prize for the first artificial single-enantiomer catalysts.

Kozlowski and her colleagues are laying the groundwork for the next generation of such catalysts, using techniques that combine empirical observation and computational tools.

In her presentation, Kozlowski will provide an overview of her lab efforts, culminating in the synthesis of natural products, such as nigerone and cercosporin, as well as pharmaceutical agents, such as a Wyeth opiate antagonist.