Drugs to treat cancer are often very expensive to produce, resulting in high costs for the patients who need them. Thanks to pioneering research by UCLA chemists led by organic chemistry professor Ohyun Kwon, the price of drug treatments for cancer and other serious diseases may soon plummet.
A chemical used in some cancer drugs, for example, costs drug companies $3,200 per gram — 50 times more than a gram of gold. UCLA researchers devised an inexpensive way to produce this drug molecule from a chemical that costs just $3 per gram. They were also able to apply the process to produce many other chemicals used in medicine and agriculture for a fraction of the usual cost.
This feat was published in the journal Science, involves a process known as “aminodealkenylation”. Using oxygen as a reagent and copper as a catalyst to break the carbon-carbon bonds of several different organic molecules, the researchers replaced those bonds with carbon-nitrogen bonds, converting the molecules into ammonia derivatives called amines.
Because amines interact strongly with molecules in living plants and animals, they are widely used in pharmaceuticals as well as agricultural chemicals. Known amines include nicotine, cocaine, morphine and amphetamine, and neurotransmitters such as dopamine. Fertilizers, herbicides, and pesticides also contain amines.
The industrial production of amines is therefore of great interest, but the raw materials and reagents are often expensive and the processes may require many complex steps to complete. Using fewer steps and no expensive ingredients, the process developed at UCLA can produce valuable chemicals at a much lower cost than current methods.
“This has never happened before,” Kwon said. “Traditional metal catalysis uses expensive metals such as platinum, silver, gold and palladium, and other precious metals such as rhodium, ruthenium and iridium. But we use oxygen and copper, one of the most abundant base metals in the world .”
The new method uses a form of oxygen called ozone, a powerful oxidant, to break the carbon-carbon bond in hydrocarbons called alkenes, and a copper catalyst to couple the broken bond to nitrogen, turning the molecule into an amine. In one example, researchers produced a c-Jun N-terminal kinase inhibitor — an anticancer drug — in just three chemical steps, instead of the 12 or 13 steps previously needed. The cost per gram can thus be reduced from thousands of dollars to just a few dollars.
In another example, the protocol took only one step to convert adenosine — a neurotransmitter and DNA building block that costs less than 10 cents per gram — into the amine N6-methyladenosine. The amine plays critical roles in controlling gene expression in cellular, developmental and disease processes, and its production cost was previously $103 per gram.
Kwon’s research team was able to modify hormones, pharmaceutical reagents, peptides and nucleosides into other useful amines, showing the potential of the new method to become a standard production technique in drug manufacturing and many other industries.
The research was funded by the National Institutes of Health.