Studies toward the total synthesis of the analgesic natural product chimonanthine and its analogues

A major area of concern for Canada’s health system is the treatment of chronic pain, which affects more than 18 per cent of Canadians and costs the health system close to $10 billion per year. More people are disabled by chronic pain than cancer or heart disease. New structurally-novel analgesics (painkillers) with unique modes of action have proven promising. One class of these molecules are the pyrrolidinoindolines, which are alkaloids (naturally occurring compounds produced by living organisms, many known for their medicinal properties). The alkaloid (-)-chimonanthine has recently been extracted from the leaves of the wintersweet, a flowering plant originating from China. This compound has been found to exhibit analgesic effects. Unlike other opiods, such as cocaine, heroin, morphine, and codeine, chimonanthines do not possess addictive properties. Using novel techniques in synthetic chemistry, Baldip Kang is working to synthesize (-)-chimonanthine. This work is a precursor to developing analogues for this compound – drugs that differ in minor aspects of molecular structure from the parent drug, synthesized so that they have more potent effects or fewer side effects. He’s focusing on determining the most efficient and cost-effective way to synthesize the molecules. He and colleagues will collaborate with a pharmaceutical company to test the analogues in pre-clinical trials, determining modifications to the structure that will further enhance the drug’s effectiveness. Through the efficient synthesis of (-)-chimonanthine and its analogues, Kang’s research promises new ways to treat chronic pain ailments.