Navigation Links
Caltech chemists devise chemical reaction that holds promise for new drug development
Date:1/11/2012

PASADENA, Calif. -- 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 teamled by Brian Stoltz, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry, and Doug Behenna, a scientific researcherused 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 saysnot 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 themonly 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."


'/>"/>
Contact: Deborah Williams-Hedges
debwms@caltech.edu
626-395-3227
California Institute of Technology
Source:Eurekalert  

Related medicine news :

1. Caltech research helps paraplegic man stand and move legs voluntarily
2. Caltech biologists discover microRNAs that control function of blood stem cells
3. Caltech scientists uncover structure of key protein in common HIV subgroup
4. Rice chemists cram 2 million nanorods into single cancer cell
5. UF medicinal chemists modify sea bacteria byproduct for use as potential cancer drug
6. Breathing easy: LSU biochemists offer first 3-D model of asthma-causing inflammation enzyme
7. MIT chemists engineer plants to produce new drugs
8. Scientists devise targeted therapy strategy for rare form of childhood cancer
9. New drug screening identifies chemical agents with potent anti-cancer activity
10. UM researcher develops new way to assess risk for chemicals
11. Elsevier and Federation of Biochemical Societies launch new journal
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Caltech chemists devise chemical reaction that holds promise for new drug development
(Date:4/29/2016)... , ... April 29, 2016 , ... ... Spiritual Awakening , announces the addition Onnit brand Alpha BRAIN and New Mood ... of Onnit brain and mood optimization products to the store is just one ...
(Date:4/29/2016)... ... , ... On Tuesday, April 26, 2016 members of the HomeTown Health network, ... Nathan Deal on SB 258, the “Rural Health Care Relief” Bill. , The bill, ... credit to individuals and corporations which donate directly to a “rural hospital” in Georgia, ...
(Date:4/29/2016)... Torrance, CA (PRWEB) , ... April 29, 2016 ... ... physician advocating optimistic healthcare awareness and author of best seller "LOVE, MEDICINE and ... Talk Radio Monday, May 2, 2016 and podcasted thereafter . Dr. Bernie ...
(Date:4/29/2016)... (PRWEB) , ... April 29, 2016 , ... Conditions were ... at Cove Island Park on Sunday, with sunny skies, a light breeze and temperatures ... nearly $33,000. , The 5k Run and Walk and 1-mile walk were ...
(Date:4/29/2016)... ... April 29, 2016 , ... A ... born with severe congenital diaphragmatic hernia have better survival rates if surgery is ... hernia (CDH)—a condition where the diaphragm fails to form completely, letting abdominal organs ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... , April 27, 2016 Shire plc ... Jeff Poulton , Chief Financial Officer, will present at the ... Boston, MA on Wednesday, May 04, 2016, 10:00 ... will be available on the Presentations and Webcasts section of ... of the webcast will be available on this same website ...
(Date:4/27/2016)... 27, 2016 Oasmia Pharmaceutical ... of a new generation of drugs within human ... results for Paclical/Apealea in the Phase III study ... epithelial ovarian cancer. These preliminary results showed non-inferiority ... with carboplatin versus Taxol in combination with carboplatin. ...
(Date:4/27/2016)... , April 27, 2016 ... reach USD 2.06 billion by 2022, according to ... Increasing consumer awareness towards a healthy lifestyle is ... seven years.      (Logo: http://photos.prnewswire.com/prnh/20150105/723757 ... coupled with rising health treatment expenditure has urged ...
Breaking Medicine Technology: