Lignin is a component of wood and endows it with its flexibility. For the production of paper, it needs to be removed in order to prevent yellowing and increase the strength of the paper. That leads to large amounts of unwanted lignin, which has been awaiting re-utilization for many years. While this problem has been partially solved by recent methods for the depolymerisation of lignin, the use of the resulting products has remained untouched so far. Prof. Katalin Barta and coworkers from the University of Groningen developed an elegant catalytical method for the use of renewable lignocellulose (woodchips). They were curious to search for a concrete use of the newly generated products. In collaboration with the department “Drug Design and Optimization” of Prof. Anna Hirsch from the HIPS, a branch of the Helmholtz Centre for Infection Research (HZI), the scientists realised that the lignin derivatives they generated are structurally similar to some pharmaceuticals. This makes them an excellent starting point for the synthesis and optimisation of drug candidates. Their nature-inspired approach has the advantage of skipping the lengthy and waste-generating synthetic routes hitherto needed for their production from petrochemicals.
A prominent class of drugs are benzazepines such as the anti-anxiety drug diazepam. The traditional multi-step synthesis generates equal amounts of both waste and the desired benzazepines, whilst the new method relies on waste-free, catalytic methods using nontoxic, recyclable and biodegradable solvents to convert unwanted lignin into benzazepine derivatives. The new compounds feature potent anticancer and/or antibacterial activity in bacterial and human cells and thus represent a promising starting point for the development of future pharmaceuticals. The authors acknowledge funding from the European Research Council; the Talent Scheme research programme, which is partly funded by the Dutch Research Council; and the Helmholtz Association’s Initiative and Networking Fund.
Original publication:
S. Elangovan, A. Afanasenko, J. Haupenthal, Z. Sun, Y. Liu, A. K. H. Hirsch, K. Barta: From Wood to Tetrahydro-2-benzazepines in Three Waste-Free Steps: Modular Synthesis of Biologically Active Lignin-Derived Scaffolds. ACS Central Science 2019, doi: 10.1021/acscentsci.9b00781
