New Chemical Reaction Method Accelerates Indole Production

A new chemical reaction pioneered by researchers from the University of Toronto (Toronto, ON, Canada) simplifies the production process for indole rings, a basic molecular frameworks commonly used in pharmaceutical products such as cholesterol-reducing drugs.

An indole is a benzene ring that is made of a six-member carbon-containing ring attached to a five-member nitrogen-containing ring. To make these privileged structures, researchers use a palladium catalyst to form two chemical bonds: a nitrogen–carbon and a carbon–carbon formation. These indole-containing compounds can then be used to produce known chemical agents, a lead structure, or a new derivative for a pharmaceutical. “This new process shortens the process for making the indole skeleton and to produce compounds that could not be made easily by other methods,” says Mark Lautens, a University of Toronto professor who codeveloped the technique with graduate student Eric Fang.

The palladium catalyst is designed to be quick and cost-effective. “It uses relatively inexpensive, commercially available material starting materials and takes only 2 or 3 steps to get to the final product,” explains Lautens. Typical processes require 6–10 steps to complete.

In addition, the researchers use boronic acid to make the carbon–carbon bond, which is more environmentally friendly than many of the alternatives currently available. “To make a hundred kilograms of these best-selling drugs, there are often hundreds of liters of solvent used, not to mention the many purification processes involved,” says Lautens. “This reaction is a cleaner, more-efficient chemistry that would eliminate multireactions and thus saves on solvents, which are often considered a hazardous waste.”

Although the technology is not currently being used for commercial use, the researchers hope to partner with a pharmaceutical company to modify the process for large-scale production. The University of Toronto filed a provisional patent for the technique in March 2005 and licensed the technology to the university’s innovations foundation.

–Kaylynn Chiarello