Baran and his team began collaborating with fellow Scripps Research chemistry Professor Donna Blackmond and members of her laboratory to study how Langlois's reagent works and to optimize its use, including the selection of trifluoromethylation sites on target compounds using certain solvents. With the optimized technique, they showed that they could directly and easily trifluoromethylate a variety of test compounds, including the natural malaria drug quinine and the synthetic anti-smoking drug varenicline (Chantix).
"The collaboration with Donna Blackmond and her lab was crucial in enabling us to improve the procedure and to understand why certain modifications led to those improvements," said Baran.
The new technique in principle makes it more feasible for pharmaceutical companies to modify and improve specific drug compounds of interest. It also means that these companies can expand the existing compound libraries they use for drug-discovery screening by making trifluoromethylated versions of these compounds quickly and easily.
"In one instance, a chemist at Pfizer told me that the trifluoromethylated compound we made in one step with our technique would have taken at least eight steps using standard techniques," said Baran.
The Baran and Blackmond labs are now working on new reagents that may be used in this reaction and ways to enable fine control of trifluoromethylation sites. "The interplay of the two labs at the nexus of synthesis and mechanistic analysis is driving this project forward in new and exciting directions," Baran said.
|Contact: Mika Ono|
Scripps Research Institute