Featured Research

from universities, journals, and other organizations

Chemists devise chemical reaction that holds promise for new drug development

Date:
January 25, 2012
Source:
California Institute of Technology
Summary:
Scientists have devised a new method for making complex molecules. The reaction they have come up with should enable chemists to synthesize new varieties of a whole subclass of organic compounds called nitrogen-containing heterocycles, thus opening up new avenues for the development of novel pharmaceuticals and natural products ranging from chemotherapeutic compounds to bioactive plant materials such as morphine.

The extensive suite of robotics in the Caltech Center for Catalysis and Chemical Synthesis enabled Brian Stoltz and his colleagues to discover the new alkylation reaction.
Credit: Caltech

A team of researchers at the California Institute of Technology (Caltech) has devised a new method for making complex molecules. The reaction they have come up with should enable chemists to synthesize new varieties of a whole subclass of organic compounds called nitrogen-containing heterocycles, thus opening up new avenues for the development of novel pharmaceuticals and natural products ranging from chemotherapeutic compounds to bioactive plant materials such as morphine.

The team -- led by Brian Stoltz, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry, and Doug Behenna, a scientific researcher -- used a suite of specialized robotic tools in the Caltech Center for Catalysis and Chemical Synthesis to find the optimal conditions and an appropriate catalyst to drive this particular type of reaction, known as an alkylation, because it adds an alkyl group (a group of carbon and hydrogen atoms) to the compound. The researchers describe the reaction in a recent advance online publication of a paper in Nature Chemistry.

"We think it's going to be a highly enabling reaction, not only for preparing complex natural products, but also for making pharmaceutical substances that include components that were previously very challenging to make," Stoltz says. "This has suddenly made them quite easy to make, and it should allow medicinal chemists to access levels of complexity they couldn't previously access."

The reaction creates compounds called heterocycles, which involve cyclic groups of carbon and nitrogen atoms. Such nitrogen-containing heterocycles are found in many natural products and pharmaceuticals, as well as in many synthetic polymers. In addition, the reaction manages to form carbon-carbon bonds at sites where some of the carbon atoms are essentially hidden, or blocked, by larger nearby components.

"Making carbon-carbon bonds is hard, but that's what we need to make the complicated structures we're after," Stoltz says. "We're taking that up another notch by making carbon-carbon bonds in really challenging scenarios. We're making carbon centers that have four other carbon groups around them, and that's very hard to do."

The vast majority of pharmaceuticals being made today do not include such congested carbon centers, Stoltz says -- not so much because they would not be effective compounds, but because they have been so difficult to make. "But now," he says, "we've made it very easy to make those very hindered centers, even in compounds that contain nitrogen. And that should give pharmaceutical companies new possibilities that they previously couldn't consider."

Perhaps the most important feature of the reaction is that it yields almost 100 percent of just one version of its product. This is significant because many organic compounds exist in two distinct versions, or enantiomers, each having the same chemical formula and bond structure as the other, but with functional groups in opposite positions in space, making them mirror images of each other. One version can be thought of as right-handed, the other as left-handed.

The problem is that there is often a lock-and-key interaction between our bodies and the compounds that act upon them -- only one of the two possible hands of a compound can "shake hands" and fit appropriately. In fact, one version will often have a beneficial effect on the body while the other will have a completely different and sometimes detrimental effect. Therefore, it is important to be able to selectively produce the compound with the desired handedness. For this reason, the FDA has increasingly required that the molecules in a particular drug be present in just one form.

"So not only are we making tricky carbon-carbon bonds, we're also making them such that the resulting products have a particular, desired handedness," Stoltz says. "This was the culmination of six years of work. There was essentially no way to make these compounds before, so to all of a sudden be able to do it and with perfect selectivity… that's pretty awesome."

In addition to Stoltz and Behenna, other authors on the paper, "Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams," include Yiyang Liu, Jimin Kim, David White, and Scott Virgil of Caltech, and Taiga Yurino, who visited the Stoltz lab on a fellowship supported by the Japan Society for the Promotion of Science. The work was supported by the King Abdullah University of Science and Technology, the NIH-NIGMS, the Gordon and Betty Moore Foundation, Amgen, Abbott, and Boehringer Ingelheim.


Story Source:

The above story is based on materials provided by California Institute of Technology. The original article was written by Kimm Fesenmaier. Note: Materials may be edited for content and length.


Journal Reference:

  1. Douglas C. Behenna, Yiyang Liu, Taiga Yurino, Jimin Kim, David E. White, Scott C. Virgil, Brian M. Stoltz. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams. Nature Chemistry, 2011; DOI: 10.1038/nchem.1222

Cite This Page:

California Institute of Technology. "Chemists devise chemical reaction that holds promise for new drug development." ScienceDaily. ScienceDaily, 25 January 2012. <www.sciencedaily.com/releases/2012/01/120112095849.htm>.
California Institute of Technology. (2012, January 25). Chemists devise chemical reaction that holds promise for new drug development. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2012/01/120112095849.htm
California Institute of Technology. "Chemists devise chemical reaction that holds promise for new drug development." ScienceDaily. www.sciencedaily.com/releases/2012/01/120112095849.htm (accessed July 25, 2014).

Share This




More Matter & Energy News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
Creative Makeovers for Ugly Cellphone Towers

Creative Makeovers for Ugly Cellphone Towers

AP (July 24, 2014) Mobile phone companies and communities across the country are going to new lengths to disguise those unsightly cellphone towers. From a church bell tower to a flagpole, even a pencil, some towers are trying to make a point. (July 24) Video provided by AP
Powered by NewsLook.com
Algonquin Power Goes Activist on Its Target Gas Natural

Algonquin Power Goes Activist on Its Target Gas Natural

TheStreet (July 23, 2014) When The Deal's Amanda Levin exclusively reported that Gas Natural had been talking to potential suitors, the Ohio company responded with a flat denial, claiming its board had not talked to anyone about a possible sale. Lo and behold, Canadian utility Algonquin Power and Utilities not only had approached the company, but it did it three times. Its last offer was for $13 per share as Gas Natural's was trading at a 60-day moving average of about $12.50 per share. Now Algonquin, which has a 4.9% stake in Gas Natural, has taken its case to shareholders, calling on them to back its proposals or, possibly, a change in the target's board. Video provided by TheStreet
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