Electric car batteries inspire a safer and less expensive way to make compounds used in medicines

Now scientists at Scripps Research, inspired by the sophisticated electrochemistry of these batteries, have developed a battery-like system that allows them to make potential advances in drug manufacturing.

Their new method, reported today in Science, avoids the safety risks associated with a type of chemical reaction called dissolution metal reduction, which is often used to produce compounds used in the manufacture of drugs. Their method would offer huge advantages over current methods of chemical manufacturing, but so far it has been largely ruled out for safety reasons.

"The types of batteries we use today in our electric cars were far too dangerous for commercial use a few decades ago, but they are now remarkably safe thanks to advances in chemistry and engineering. Phil Baran, Ph.D., is the Darlene Shiley Chair in Chemistry at Scripps Research and is the lead author of Science paper. "By applying some of the principles that made this new generation of batteries possible, we have developed a method for safely conducting highly reducing chemical reactions that have very rarely been widely used because, until they were too dangerous or too expensive. "

"This could have a major impact not only on the manufacture of pharmaceuticals," adds Baran, "but also on the mindset of chemists specializing in the field of drug chemistry who traditionally avoid such chemistry for safety reasons author Michael Collins, a medicinal chemist at Pfizer, precisely for this reason ".

One of the most powerful reactions, and representative examples of this deeply reductive chemistry used by chemists to make new molecules, is the Birch reduction, largely initiated by the Australian chemist Arthur Birch in the 1940s. Reducing reaction involves the dissolution of a reactive metal in liquid ammonia in order to manipulate ring-shaped molecules that can serve as a basis for the manufacture of many chemicals, including drug molecules .

The procedure requires condensing ammonia or similar compounds, corrosive, toxic and volatile, and combining it with metals such as lithium, which can ignite if they are exposed to # 39; air. The process must take place at extremely cold temperatures, requiring expensive equipment and specialists.

A rare example of the use of a dissolving metal reduction in the manufacture of pharmaceuticals is a drug candidate (sumanirole) for Parkinson's disease developed by Pfizer, a remarkable achievement in the manufacture of chemicals requiring a Herculean effort. The system for producing the compound on a large scale requires enough gaseous ammonia to fill three Boeing 747 airliners and must be driven at -35 degrees Celsius. Pfizer's efforts to use this chemistry testify to the synthetic power of the reaction and the great desire to use it in large-scale manufacturing compared to any known method.

To overcome these significant barriers to using this chemistry, Baran and his team examined advances in battery manufacturing by partnering with University of Utah experts led by Shelley Minteer. Ph.D., and the University of Minnesota. by Matthew Neurock, Ph.D.

Lithium-ion (Li-ion) batteries used in modern electronics, such as cell phones, laptops and electric cars, rely on the advances of an internal component called the Interphase with solid electrolyte (SEI). The SEI is a protective layer that forms on one of the electrodes inside a Li-ion when the battery is charged for the first time and allows the battery to be charged recharged. The production of safe and efficient batteries currently used in consumer electronics has been based on years of optimization of chemical conditions – composition of electrolytes, solvents and additives – at the origin of UTE.

The team noted that the reaction that forms the UTE in batteries is an electrochemical reaction similar to the reaction of Birch and his loved ones. They assumed that they could borrow from what the battery manufacturers had learned to use a safe and convenient method for conducting an electroreduction reaction.

"In many ways, you envision similar situations – powerful reactions that, when they are effectively exploited, can prove extremely useful," said Solomon Reisberg, a graduate student at Baran Lab. 39, one of the co-authors of the book. Science paper. "The team took advantage of the hard-won knowledge of the conditions that make reducing electrochemistry in batteries practical and used it to rethink how much reductive chemistry can be used on a large scale."

The Scripps research team began by testing a range of additives used to prevent the overloading of Li-ion batteries and discovered that a combination of two substances, dimethylurea and TPPA, made it possible to perform the Birch reaction. at room temperature.

By testing various other materials used in the batteries, the Baran team has developed a set of conditions allowing them not only to perform reductive electrosynthesis safely, but also to increase the versatility of the reaction. to create a greater variety of products, which was not possible with previous electrochemical solutions. methods.

This method avoided the need to dissolve liquid metals in large quantities of ammonia – as well as the cost and associated risks – and instead used an electrolyte system similar to that used in batteries. In addition to the Birch reaction, researchers have been able to apply this technique to other types of powerful reactions, often used in synthesis but rarely, if ever, in an industrial setting.

The researchers synthesized several versions of important single-cycle compounds, as well as molecules combining multiple rings to create more complex structures, skeletal structures for drugs and other chemicals. In contrast to the extremely expensive equipment that previously required large-scale reducing chemistry, the team collaborated with Asymchem Life Science, a Tianjin-based chemical manufacturer in China, to build a small modular device capable of generating large product quantities $ 250.

"This shows that it is possible to produce a scale synthesis of the kilogram of constituent blocks relevant from a pharmaceutical point of view by adapting what we have learned about electrochemistry thanks to the rapid progress of the battery technology, "says Baran. "We anticipate that this will bring a boon to the industry, ultimately allowing it to materialize these reactions."

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More information:
"Evolutionary and Safe Synthetic Organic Electro-Reduction Inspired by the Chemistry of Li-ion Batteries" Science (2019). science.sciencemag.org/cgi/doi… 1126 / science.aav5606