Easier, cheaper way to make a sought-after chemical modification to pharmaceuticals

Scientists at The Scripps Research Institute have devised a much easier technique for performing a chemical modification used widely in the synthesis of drugs and other products.

Known as ''trifluoromethylation,'' the modification adds a CF₃ molecule to the original compound, often making it more stable - and, for a drug, keeping it in the body longer.

With the new technique, chemists can perform this feat using a relatively simple, safe, room-temperature procedure and can even select the site of the modification on the target compound.

''I've been presenting this methodology at several pharma companies, and there's a lot of interest-so much so that their chemists are starting to use it,'' said Scripps Research Professor Phil S Baran, senior author of the new study, scheduled for publication the week of August 15, 2011, in an advance online edition of the Proceedings of the National Academy of Sciences.

Standard procedures for trifluoromethylation involve gases and associated hardware, high heat, metal catalysts, and oxidants. ''The procedures are often prohibitively complicated, and medicinal chemists often don't have the time or the resources to get into it,'' said Baran.

Inspired by frequent consulting visits to pharmaceutical companies, Baran and his lab began to look for simpler ways to perform trifluoromethylation. After running more than 500 different reaction setups on a test compound, they found just one that delivered significant quantities of the desired reaction product. It was a simple setup that used a reagent known as sodium trifluoromethanesulfinate, an inexpensive chemical that is stable at room temperature.