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New production method could make cheaper drug treatments possible

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UCLA new drug production method

UCLA researchers have devised a way to produce chemicals used in medicine for a fraction of the usual cost.

Drugs to treat cancer are generally very expensive to produce, but new research by UCLA chemists could lead to the price of drug treatments for cancer and other serious illnesses may soon plummet.

One chemical used in some anti-cancer drugs, for example, costs pharmaceutical companies $3,200 per gram — 50 times more than a gram of gold.

The UCLA researchers, led by organic chemistry professor Ohyun Kwon, devised an inexpensive way to produce this drug molecule from a chemical costing just $3 per gram. They were also able to apply the process to produce many other chemicals used in medicine for a fraction of the usual cost.

The study, 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 many different organic molecules, the researchers replaced these bonds with carbon-nitrogen bonds, converting the molecules into derivatives of ammonia called amines.

Because amines interact strongly with molecules in living plants and animals, they are widely used in pharmaceuticals, as well as in agricultural chemicals. Familiar amines include nicotine, cocaine, morphine and amphetamine, and neurotransmitters like dopamine. Fertilizers, herbicides and pesticides also contain amines.

In addition to high costs, the processes used to create these raw materials can come with a long list of complicated steps to complete. UCLA scientists say this new process takes fewer steps and requires no expensive ingredients.

“This has never been done 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 are using oxygen and copper, one of the world’s most abundant base metals.”

The new method uses a form of oxygen called ozone, a potent oxidant, to break the carbon-carbon bond in hydrocarbons called alkenes, and a copper catalyst to couple the broken bond with nitrogen, turning the molecule into an amine. In one example, the researchers produced a c-Jun N-terminal kinase inhibitor — an anti-cancer 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 just 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 a crucial role in controlling gene expression in cellular, developmental and disease processes. Its production cost has previously been $103 per gram.

Kwon’s research group was able to modify hormones, pharmaceutical reagents, peptides and nucleosides into other useful amines. The new method could become a standard production technique in drug manufacturing and other industries.

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