Clean synthetic strategies to dopamine-based biologically active molecules from lignin: A green path to drug discovery

Abstract

The structural complexity of renewable resources offers remarkable opportunities for the environmentally friendly manufacturing of essential pharmaceuticals, yet this has not been adequately addressed due to the lack of suitable methods. Our here described approach to drug discovery, builds on the innate structural features of the aromatic moiety of lignin to enable green pathways to various classes of biologically active molecules of the core dopamine structure. The catalytic transformations are atom-economic, produce only harmless side-products and use benign reaction media, including tunable deep eutectic solvents for modulating reactivity in challenging cyclization steps. Biological screening and chemical similarity searches identified promising anti-infective, anti-inflammatory, and anticancer activities. The frontrunners show outstanding metabolic stability and in vivo activity against Streptococcus pneumoniae infection, highlighting the power of our strategy.