Navigation Links
Scientists find easier, cheaper way to make a sought-after chemical modification to drugs

LA JOLLA, CA August 15, 2011 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 stableand, 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 interestso 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.

Chemists had long believed that this reagent was unsuitable for trifluoromethylating a broad class of molecules frequently found in drug compounds, and also that the reagent required the use of catalyzing metal salts. But in this initial screening, the reagent, known as Langlois's reagent for its discoverer, the French chemist Bernard R. Langlois, seemed to work even without such constraints.

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

Related biology news :

1. Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells
2. Scientists identify novel inhibitor of human microRNA
3. Argonne scientists peer into heart of compound that may detect chemical, biological weapons
4. MU scientists go green with gold, distribute environmentally friendly nanoparticles
5. Scientists identify gene that may contribute to improved rice yield
6. Scientists discover why a mothers high-fat diet contributes to obesity in her children
7. MU scientists see how HIV matures into an infection
8. Earth scientists keep an eye on Texas
9. Thinking it through: Scientists call for policy to guide biofuels industry toward sustainability
10. Scientists identify a molecule that coordinates the movement of cells
11. Scientists Find new migratory patterns for Mediterranean and Western Atlantic bluefin tuna
Post Your Comments:
Related Image:
Scientists find easier, cheaper way to make a sought-after chemical modification to drugs
(Date:10/29/2015)... 29, 2015  Rubicon Genomics, Inc., today announced ... of its DNA library preparation products, including the ... ThruPLEX Plasma-seq kit. ThruPLEX Plasma-seq has been optimized ... NGS libraries for liquid biopsies--the analysis of cell-free ... applications in cancer and other conditions. Eurofins Scientific ...
(Date:10/27/2015)... YORK , Oct. 27, 2015 In ... major issues of concern for various industry verticals such ... is due to the growing demand for secure & ... in various ,sectors, such as hacking of bank accounts, ... for electronic equipment such as PC,s, laptops, and smartphones ...
(Date:10/26/2015)... and LAS VEGAS , Oct. ... Labs , an innovator in modern authentication and a ... announced the launch of its latest version of the ... enabling organizations to use standards-based authentication that supports existing ... S3 Authentication Suite is ideal for organizations deploying customer-facing ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... Mass. , Dec. 1, 2015 Researchers ... the McGovern Institute for Brain Research at MIT have ... that significantly cut down on "off-target" editing errors. The ... in the use of genome editing. Science ... that changing three of the approximately 1,400 amino acids ...
(Date:12/1/2015)... 2015 ... "2016 Europe Cell Surface Markers: Country ... Strategies, Opportunities for Suppliers--France, Germany, Italy, Spain, ... --> ) has announced the ... Surface Markers: Country Volume and Sales Forecasts, ...
(Date:12/1/2015)... FRANCISCO , Dec. 1, 2015  Symic, a ... affect the extracellular matrix (ECM), today announced that it ... to advance the company,s pipeline, including its lead candidates ... Ventures and includes the participation by all existing major ... funding brings the total capital raised by Symic to ...
(Date:12/1/2015)... ) has ... Virology and Bacteriology Testing Market: Sales and ... Shares by Test, Innovative Technologies, Competitive Strategies, ... --> ) has announced the ... Bacteriology Testing Market: Sales and Volume Segment ...
Breaking Biology Technology: