Author: Liu Amy
Date: June 2008
Pharmaceutical companies may be able to make better drugs with fewer side effects using a new synthesis method recently developed by a Duke University chemist. Don Coltart, assistant professor of chemistry at Duke, has published a paper in the European journal Angewandte Chemie that describes a new way of synthesizing a class of molecules, called ketones, in a way that is faster, cheaper, and more efficient than current methods.
Just as your right and left hands are mirror images of one another, but are not identical, molecules can also be non-identical mirror images, though they contain exactly the same types of atoms. Such molecules are described as being enantiomers of one another, and molecules with this property are said to have chirality. Chiral molecules are particularly important in pharmaceuticals because their effects in the body sometimes differ drastically. While one molecule may be useful in medicine, its chiral isomer may have useless or even harmful properties. One infamous example is the drug thalidomide, a morning sickness drug prescribed to pregnant women in the 1960s. Though one configuration of the thalidomide molecule had the intended medicinal effects, its chiral isomer, or mirror image shape, caused severe birth defects in the children of women who took the drug.
Though pharmaceutical companies are aware of the importance of chiral molecules, selectively synthesizing only one enantiomer of a drug on a commercial scale can be costly, time-consuming, and complicated using current methods. Asymmetric synthesis, the process of creating molecules of only one shape, is commonly performed commercially with the use of extreme conditions, such as temperatures of -100 degrees Celsius.
Coltart's method, however, can be done at the temperature range of -40 to 0 degrees Celsius, relatively mild for such processes, and is up to 98 percent effective in synthesizing the intended enantiomer. Coltart's process involves the use of "chiral auxilaries," or small molecules that attach to the molecule being synthesized and help direct the addition of new parts of the molecule. This control over the shape of the molecule allows the creation of the intended enantiomer of the ketone molecule. The auxiliary molecules can also be easily detached at the end of the chemical reaction and recycled for use in further drug synthesis, making the process more cost-effective.
Drug companies, according to Coltart, may be able to use the synthetic technique on a commercial scale to produce drugs that are purer and have fewer side effects. Samuel Danishefsky, who is a Columbia University professor, researcher at the Memorial Sloan-Kettering Cancer Center, and Coltart's formal post-doctoral mentor, praised Coltart for his innovation in developing the synthesis method. "You could have had a hundred people look at this problem and not see it the way he did," said Danishefsky. "It's a very nice idea."
Written by Amy Liu
Reviewed by Jeff Kost
Published by Pooja Ghatalia