Researchers have been working on finding uses for the lignin component that’s a by-product of paper production. Lignin consists of cross-linked phenolic compounds that give wood its strength. The lignin is removed during paper production to prevent paper from yellowing and to increase the paper’s strength. A huge amount of unwanted lignin is generated during the process, and scientists discovered that lignin derivatives share many complex structural features with modern pharmaceuticals, making them ideal starting materials to synthesize potential drug candidates. The researchers realized that by exploiting the lignin’s similarity with pharmaceutical ingredients, they could bypass the wasteful, laborious process of deriving these ingredients from petrochemicals.

Using renewable wood chips, researchers were able to produce pharmaceutically relevant compounds in just two or three steps with water as the only waste product. Making these compounds has typically produced hazardous waste because large amounts of flammable solvents are used during the processes, which also require several steps to make the complex drugs. One drug class, benzazepines, which includes the anti-anxiety drug diazepam, was focused on during the research. Conventional multistep synthesis using flammable solvents generates roughly equal amounts of waste and benzazepines. In the newly created process by researchers, catalytic methods are combined with nontoxic, recyclable, and biodegradable solvents to convert monomers derived from lignin into benzazepine derivatives without producing waste. Several new compounds also show antibacterial or anticancer activity in bacterial and human cells.

The research “From Wood to Tetrahydro-2-benzazepines in Three Waste-Free Steps: Modular Synthesis of Biologically Active Lignin-Derived Scaffolds” was published in ACS Central Science, and the authors acknowledge funding from the European Research Council; the Talent Scheme research program, which is partly funded by the Dutch Research Council; and the Helmholtz Association’s Initiative and Networking Fund.