Featured Research

from universities, journals, and other organizations

Scientists find easier, cheaper way to make a sought-after chemical modification to pharmaceuticals

Date:
August 15, 2011
Source:
The Scripps Research Institute
Summary:
Scientists have devised a much easier technique for performing a chemical modification used widely in the synthesis of drugs and other products.

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.

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.

The two first authors of the paper, "Innate C-H Trifluoromethylation of Heterocycles," are Yining Ji and Tobias Brueckl of the Scripps Research Baran lab. Others who contributed are Ryan D. Baxter of the Scripps Research Blackmond lab and Yuta Fujiwara, Ian B. Seiple, and Shun Su of the Baran lab.

The work was supported in part by a grant from the National Institute of General Medical Sciences, part of the National Institutes of Health.


Story Source:

The above story is based on materials provided by The Scripps Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yining Ji, Tobias Brueckl, Ryan D. Baxter, Yuta Fujiwara, Ian B. Seiple, Shun Su, Donna G. Blackmond, Phil S. Baran. Innate C-H trifluoromethylation of heterocycles. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1109059108

Cite This Page:

The Scripps Research Institute. "Scientists find easier, cheaper way to make a sought-after chemical modification to pharmaceuticals." ScienceDaily. ScienceDaily, 15 August 2011. <www.sciencedaily.com/releases/2011/08/110815162440.htm>.
The Scripps Research Institute. (2011, August 15). Scientists find easier, cheaper way to make a sought-after chemical modification to pharmaceuticals. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2011/08/110815162440.htm
The Scripps Research Institute. "Scientists find easier, cheaper way to make a sought-after chemical modification to pharmaceuticals." ScienceDaily. www.sciencedaily.com/releases/2011/08/110815162440.htm (accessed July 28, 2014).

Share This




More Matter & Energy News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Carbon Trap: US Exports Global Warming

The Carbon Trap: US Exports Global Warming

AP (July 28, 2014) AP Investigation: As the Obama administration weans the country off dirty fuels, energy companies are ramping-up overseas coal exports at a heavy price. (July 28) Video provided by AP
Powered by NewsLook.com
Shipping Crates Get New 'lease' On Life

Shipping Crates Get New 'lease' On Life

Reuters - Business Video Online (July 25, 2014) Shipping containers have been piling up as America imports more than it exports. Some university students in Washington D.C. are set to get a first-hand lesson in recycling. Their housing is being built using refashioned shipping containers. Lily Jamali reports. Video provided by Reuters
Powered by NewsLook.com
Europe's Highest Train Turns 80 in French Pyrenees

Europe's Highest Train Turns 80 in French Pyrenees

AFP (July 25, 2014) Europe's highest train, the little train of Artouste in the French Pyrenees, celebrates its 80th birthday. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
TSA Administrator on Politics and Flight Bans

TSA Administrator on Politics and Flight Bans

AP (July 24, 2014) TSA administrator, John Pistole's took part in the Aspen Security Forum 2014, where he answered questions on lifting of the ban on flights into Israel's Tel Aviv airport and whether politics played a role in lifting the ban. (July 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins