Researchers build up a basic strategy to make drug precursor

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• Source: Rice University


• Date: 27 Feb,2021

Save your silver! It’s better used for jewellery than as a catalyst for medication.

Rice University scientists have developed a greatly simplified method to make fluoroketones, precursors for drug design and manufacture that typically demand a silver catalyst.

Rice chemist Julian West and grad students Yen-Chu Lu and Helen Jordan introduced a procedure for the rapid and scalable synthesis of fluoroketones that have until now been challenging and expensive to make.

The laboratory’s new process replaces silver with cerium-based ceric ammonium nitrate (CAN), which generates functional precursors under mild conditions in about thirty minutes.

We could make batches of this in a bathtub.”

Julian West, Chemist, Rice University

Cerium has demonstrated such potential in different labs, and the fact that it’s 800 times more abundant in the Earth’s crust than silver made it of great interest to the Rice team.

“Ketones are a gateway operational group in molecules which you could use to make different things, like anti-cancer chemicals,” said West, who came to Rice in 2019 with funding from the Cancer Prevention and Research Institute of Texas and was named a Forbes 30 Under 30 science”game changer” last year.

“They’re a great foothold to turn into an alkene or an aromatic ring,” he said. “The most important part of this paper is that we’re incorporating fluorine into these fragments. Fluorine is an interesting element and very abundant, but it’s barely used in biology.

“Fluorine has some intense properties: It is incredibly electronegative, so it holds onto its electrons,” West said. “That makes it hard for enzymes in biological processes to deal with them in pharmaceuticals such as anti-cancer molecules.”

Hydrogen atoms in drug molecules are easy for the liver to process, but replacing them with fluorines”is like armor plating at that place,” he said. “That helps medication last far longer in the body, so you don’t need to take just as much. That’s desirable for chemotherapeutics.” He noticed that atorvastatin (aka Lipitor), one of the most commonly prescribed drugs in the United States, incorporates fluorine for the same purpose.

“we would like to place fluorine in specific places in the molecule where we all know it will make a difference, and this ketone functional group enables us to do it,” West said. “People have been using a silver catalyst, but the process requires a lot of silver, it takes quite a while at high temperature and it needs to be done under a carefully controlled nitrogen or argon atmosphere.

“Our process is cheap bucket chemistry, and we think the reaction is completed in about five minutes,” he said.

The practice is highly scalable. “When Yen-Chu tripled the first recipe, he got exactly the same result,” West said. “That’s rare in these kinds of reactions.”