The ability to produce a specific enantiomer, and not its mirror-image form, has long been a goal of researchers. A team from the California Institute of Technology has proposed a method for creating molecules with carbon–carbon in only one of their handed forms, using materials that are abundant and inexpensive.
“This method can make the discovery and synthesis of bioactive compounds, such as pharmaceuticals, less expensive and less time-consuming than was possible with previous methods,” noted Norman Chandler Professor of Chemistry Gregory Fu. “A drug developer could use our method to more easily make libraries of candidate drugs, which they would then test for a desired activity.”
The team engineered various classes of compounds with a specific chirality, including beta-lactams, of which the antibiotic penicillin is a member.
“The nickel catalysts work like the mold of a glove, shaping a molecule into the desired left or right hand. You could, in theory, use our method to more easily make a series of penicillin-like molecules, for example,” said Fu.
Molecules with different handedness can have surprisingly different traits. For example, the artificial sweetener aspartame has two enantiomers—one tastes sweet while the other has no taste. Ibuprofen contains both left- and right-handed forms, but only one version is therapeutic.
Next steps for the researchers are to develop their method to allow them to control the handedness at two sites within a molecule rather than just one, providing drug designers with even more flexibility.