Acetaminophen—the active ingredient in many Americans’ go-to pain reliever, Tylenol—typically stems from a surprising source: coal tar, a viscous liquid produced when oxygen-deprived coal is subjected to high heat.
But a new method developed by researchers at the University of Wisconsin–Madison’s Great Lakes Bioenergy Research Center (GLBRC) offers an environmentally friendly alternative to this fossil fuel-heavy process, drawing on a natural compound derived from plant material to synthesize the popular medication. Per a press release, the technique is outlined in a patent recently awarded to a team led by UW-Madison biochemist John Ralph.
Ralph—along with biochemist Justin Mobley, who is now with the University of Kentucky, and GLBRC research scientist Steven Karlen—decided to experiment with clipoffs, which are small molecules attached to lignin (an abundant yet difficult-to-manage polymer that makes plants’ cell walls rigid), after having a “eureka moment” in the middle of a conversation, reports Stephanie Blaszczyk for the Milwaukee Journal Sentinel.
“[Ralph] started talking about clipoffs, and I said why don’t we make something out of these,” Mobley, now a researcher at the University of Kentucky, tells Blaszczyk. “So we chose acetaminophen as a catchy target that people have heard and care about.”
In the UW-Madison statement, Ralph describes lignin as an “extremely complex, messy polymer … very effective for providing structure and defense for the plant” but hard to break down into usable components. According to David Wahlberg of Madison.com, this quality makes lignin a headache for researchers, who rely on plant sugars found in bioenergy crops to produce biofuels but find themselves unable to effectively use the leftover polymer, which is then burned for energy.
To circumvent this wastefulness, the scientists created a string of chemical reactions capable of converting clipoff molecules—so-called because the p-hydroxybenzoate structures attached to lignin are “fairly easy to clip off as a quite pure stream,” as Ralph explains in the statement—into acetaminophen. Blaszczyk writes that the team completed this task in just three steps, adhering to the same established process used with coal tar, so the only part "that changed was the source material.”
Both p-hydroxybenzoate and acetaminophen take relatively simple forms, with the latter manifesting as a six-carbon benzene ring with two smaller chemical groups attached. Given the similarities between the two components’ structures, the plant-derived material actually boasts an advantage over fossil fuel-derived coal tar. Whereas this more complex petrochemical must be stripped down to its molecular backbones before being built back into the desired compound, the lignin-based molecules already bear some of the desired structure.
For now, the researchers are working on refining their method and improving both the yield and purity of plant-derived acetaminophen. Although the more expensive renewable alternative is unlikely to replace the cheaper coal tar method anytime soon, Ralph tells the Journal Sentinel’s Blaszczyk that “at some point, it may be the case that we are completely prevented from using fossil fuels.
“We are not close to that now,” he concludes, “ ... but it is almost inevitable. Preparing for a future in which our resources are derived sustainably seems prudent.”