Chemistry doesn’t get more Canadian than this. Researchers at Université Laval have reported the total synthesis of Quebecol, a molecule isolated from maple syrup which may have anti-cancer properties.
A 2011 paper in the Journal of Functional Foods describes how a novel phenolic compound was isolated from maple syrup by a team from the University of Rhode Island. They named it after the province of Quebec, which produces more maple syrup than any other jurisdiction. Subsequent studies by the same group indicated that extracts containing Quebecol might have an antiproliferative effect against colon cancer cells. “If Quebecol is responsible for the activity, then it might be pretty active,” says Normand Voyer, a chemist at Laval. “But no one had enough material to test it out rigorously.”
Motivated at least partly by Canadian pride, Voyer and PhD student Sebastien Cardinal decided to take on the challenge of artificial synthesis. They used a retrosynthetic approach, trying to piece together Quebecol from readily available precursors, such as derivatives of guaiacol and mandelic acid. “It turned out to be a very nice synthesis, where we learned quite a bit of chemistry along the way,” says Voyer. For example, the step used to bring together the three aromatic rings of the polyphenol skeleton involved an unusual double Suzuki coupling reaction of dibromoalkenes. “Such reactions can potentially be used for different polyphenols, including those from other natural products,” says Voyer.
But the key outcome of the synthesis, recently published in Tetrahedron Letters, is that it is now straightforward to make grams of Quebecol, allowing more rigorous tests of its potential bioactivity. Moreover, the synthesis can easily be adapted to produce analogues and derivatives that might be even more potent. “Overcoming the scientific challenges of synthesizing a natural product, it’s really a great feeling,” says Voyer. “Also, we’re convinced that these discoveries will help other researchers advance their science and that really makes us feel good.”