Synthetic Organic Chemistry

"Synthetic" and "Organic" at the same time?

Are naturally-sourced vitamins different from the same vitamin prepared by chemical synthesis in a lab? 

It’s a question that many people may ask.  The view that organic matter is different from inorganic matter because it possesses a “vital essence” can be traced to Ancient Egypt.  Up until the early 19th century, even some chemists believed that humans might observe the organic world but could not replicate it because of this metaphysical “essence”.  Today chemists know that this is not true; the two vitamins are the same.  Further, the field of organic chemistry is the study of molecules based on carbon, which includes many natural substances as well as completely man-made materials like plastics.

Creating new compounds

In the Department of Chemistry at the University of Manitoba, Phil Hultin and his team of graduate and undergraduate student researchers are working on the synthesis of organic molecules that could potentially form the basis for new drug therapies.  They are using the technique of palladium-catalyzed cross coupling that won Heck, Negishi and Suzuki the 2010 Nobel Prize in Chemistry.

Synthetic organic chemists build complex molecules from smaller simpler molecules.  To do this, they need to be able to join carbon atoms together, but the carbon atoms in most molecules don’t easily react with one another.   In palladium-catalyzed cross coupling, molecules meet on a palladium atom and their proximity to one another kick-starts the chemical reaction that links their carbon atoms.1
 
The U of M team has already had its successes, and in 2010, research by Laina Geary (who earned her Ph.D. with Hultin in 2011) was featured in the Journal of Organic Chemistry as well as appearing on the cover of the European Journal of Organic Chemistry.  Their idea was to use trichloroethylene (TCE), a cheap and plentiful molecule, as a “scaffold” around which complex molecular structures could be constructed using simple chemical reactions.

They found that each of the chlorines on TCE could be replaced selectively by other structural units in a modular fashion, and in only two steps they could form a wide variety of cyclic compounds called “benzofurans”. 

The importance of benzofurans

Benzofuran compounds have many potential applications, but the Hultin group is most interested in their potential as drugs to treat serious fungal infections, or even deadly tropical diseases like Leishmaniasis, African Sleeping Sickness, or Chagas’ Disease.
 
The method devised by Geary and Hultin makes it very straightforward to create many structural variations on the benzofuran core.  Once the new benzofuran compounds are created, the next step is to test them for their ability to stop the growth of fungal cells.  

By testing many related structures the chemists can learn what structural features contribute to effectiveness and which features have a negative effect.  This fundamental work of scientists requires dedication, commitment and time, and the basic research of chemists, like Geary and Hultin, is the starting point of that arduous road to the development of new drugs to fight disease.

The chemical structure


 

Trichloroethylene reacts with a phenol, which may contain further attached groups “X”, “Y” etc.  The chemists isolate the product of this reaction, and submit it to a palladium-catalyzed process in which the carbon group "R" replaces one chlorine, while the other chlorine is replaced by a new carbon-carbon bond forming the benzofuran ring system.  The method works for a wide variety of phenols and “R” groups, giving the method its modular character.

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1"The Nobel Prize in Chemistry 2010 - Press Release".  Nobelprize.org. 9 Jun 2011 http://nobelprize.org/nobel_prizes/chemistry/laureates/2010/press.html

 

l-r:  Phil Hultin and Laina Geary


Trichloroethylene:  In this image, chlorine atoms are green, carbon is grey and hydrogen is white.


Intermediate product.  The oxygen atom is shown in red.


A typical benzofuran product.  In this image, "X" and "Y" are simply hydrogens, and "R" is a C6H5 ring.


RELATED LINKS


Dr. Hultin's website